HECKER SCOTT J (US)
FRECH PATRICIA (US)
DEASON MIKE (US)
DANG QUN (US)
GUSHURST KAREN (US)
YANG DONGLAI (US)
KOPCHO JOSEPH J (US)
HECKER SCOTT J (US)
FRECH PATRICIA (US)
DEASON MIKE (US)
DANG QUN (US)
GUSHURST KAREN (US)
YANG DONGLAI (US)
| WO2006023515A2 |
| US6756360B1 |
CLAIMS What is claimed is:
1. A crystalline form of a compound of Formula 1
(I)-
2. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 14.2, 14.9, 16 and 25.3.
3. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 14.2, 16.0 and 25.3.
4. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 12.6, 13.1 and 25.3, but not at 11.9 or 16.5.
5. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 12.6, 13.1 and 25.3, but not at 6.4 or 21.4.
6. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 12.6, 13.1 and 25.3, but not at 7.8, 1 1.9 or 16.5.
7. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 13.1, 14.9, 20.8 and 25.3, but not at 11.9 or 21.4.
8. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 12.6, 17.2, 20.8 and 25.3, but not at 10.0, 1 1.9 or 16.5.
9. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 12.6, 13.1, 14.2, 14.9, 17.2, 20.8 and 25.3, but not at 11.9.
10. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.3, 11.2, 12.6, 13.1, 13.5, 14.2, 14.7, 14.9, 16.0, 17.0, 17.2, 17.4, 18.3, 18.9, 19.6, 20.0, 20.2, 20.8, 22.6, and 25.3
11. The crystalline form of claim 10 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8, 10.0 11.1, 11.5, 18.0, 18.8, and 21.5.
12. The crystalline form of claim 10 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8 and 10.0.
13. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8.
14. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 10.0.
15. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 5.7, 16.2, 18.8 and 21.5.
16. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8 or 10.0 or 11.5, but not at 7.2 or 13.1.
17. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8, 10.0, 11.1, 13.6, 16.2,
18.0, 20.2, and 21.5.
18. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 5.7, 7.8, 9.4, 10.0, 1 1.1, 11.5,
12.1, 12.4, 13.6, 14.2, 15.5, 16.2, 16.9, 18.0, 18.8, 19.9, 20.2, 20.9, 21.5, 22.4, 23.2, 24.3, 25.9 and 28.1.
19. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8, 10.0, 11.1, 11.5, 13.6,
16.2, 18.0, 18.8, 20.2 and 21.5.
20. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.8, 9.4, 10.0, 11.1, 11.5, 12.1,
12.4, 13.6, 16.2, 16.9, 18.0, 18.8, 19.9, 20.2, 22.4 and 23.2.
21. The crystalline form of claim 1 , characterized by unit cell parameters approximately equal to the following: cell dimensions a = 11.4905(4)A, b = 16.3218(1O)A, c = 30.8664(17)A; space group P2i/c(No.l4); β, = 93.393(3).
22. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0 and 24.7.
23. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0, 13.1 24.7 and 27.7.
24. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0, 12.3, 13.1, 14.8,
16.5, 21.4, 24.7 and 27.7.
25. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0, 13.1 , 21.4 and 24.7.
26. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0 and 16.5.
27. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 21.4 and 24.7.
28. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 11.0, 13.1, 16.5, 21.4, 24.7, 26.5 and 27.7.
29. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 6.4, 7.1, 12.6 and 20.2.
30. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 6.4, 7.1, 11.9, 12.6, 13.1, 17.5, 19.3 and 20.2.
31. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 6.4.
32. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.1 and 12.6 but not at 7.8, 9.2, 11.0 or 16.0.
33. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 6.4, 7.1, 11.9 and 12.6, but not at 7.8 or 11.0.
34. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 9.2, 1 1.3, 12.5, 14.0 and 17.9 but not at 25.3.
35. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 12.5 and 17.9, but not at 6.4, 7.8, 24.7 or 25.3.
36. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 9.2, 11.3, 12.5, 13.5, 14.0, 17.4 and 17.9 but not at 6.4 or 25.3.
37. The crystalline form of claim 1 having an X-ray powder diffraction pattern that exhibits characteristic peaks expressed in 2-theta angles at 7.2, 9.2, 1 1.3, 12.1, 12.5, 13.5, 14.0, 14.7, 14.9, 15.1, 17.4, 17.9, 18.9 and 20.1 but not at 25.3.
38. A composition consisting essentially of the crystalline form of claim 1.
39. A composition consisting essentially of the crystalline form of any one of claims 2 -37.
40. A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier or excipient.
41. A pharmaceutical composition comprising a crystalline form of any one of claims 2 -37.
42. The crystalline form of any one claims 1-37 for the manufacture of a medicament for the prevention or treatment of a clinical condition for which an FBPase inhibitor(s) is indicated.
43. The crystalline form of any one claims 1-37 for the manufacture of a medicament for the treatment, prevention or reduction of the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels.
44. A method of treating, preventing or reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
45. A method of treating, preventing or reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
46. A method of treating, preventing or reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
47. A method of treating, preventing or reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
48. A method of treating, preventing or reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
49. A method of treating, preventing or reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
50. A method of treating, preventing or reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
51. A method of treating, preventing or reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
52. A method of treating, preventing or reducing the time to onset of increased or excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of the crystalline form of any one of claims 2-37.
53. A process of making a crystalline form of Formula I selected from Forms A-E, wherein said process comprises the step of combining the compound of Formula I with a solvent to form a mixture.
54. The process of claim 52 wherein said solvent is selected from tetrahydrofuran, methanol, acetronitrile, di-n-butyl ether, ethanol, ethyl acetate, heptane, 2-propyl ether, water, acetone, heptane, dichloromethane or a combination of any one or more of said solvents.
55. The process of claim 50, wherein said process further comprises a step of subjecting the mixture to conditions that cause said solvent to evaporate.
56. The process of claim 50, wherein said process further comprises a step of heating and cooling the mixture.
57. The process of claim 50, wherein said process further comprises the step of adding an antisolvent to said mixture. |
CRYSTALLINE POLYMORPHS
CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application Serial No.
60/949,681, filed July 13, 2007, the disclosure of which is hereby incorporated by reference in its entirety, including all figures, tables and amino acid or nucleic acid sequences.
FIELD OF THE INVENTION
The present invention relates to crystalline polymorphs of a phosphorus-containing 5-ketothiazole compound that is a potent inhibitor of fructose- 1,6-bisphosphatase (FBPase) and pharmaceutical compositions thereof as well as methods of making and using the same.
BACKGROUND OF THE INVENTION
Depending on the chemical nature of molecule, a compound may exist in an amorphous state or in a crystalline state. A crystalline form of an API may be polymorphic. A polymorph is a compound of a defined chemical composition that exists in more than one molecular arrangement or configuration in the solid state.
SUMMARY OF THE INVENTION
The present invention provides for novel crystalline polymorphic forms, or polymorphs, (Forms A-E) of 2-amino-5-(2,2-dimethylpropionyl)-4-{[5-(N,N-(2-ethoxy- carbonylprop-2-yl)phosphonamido] furan-2-yl}thiazole (the compound of Formula I) and pharmaceutical compositions and medicaments of the same. Further provided are methods of using the polymorph Forms A-E of the compound of Formula I (herein after, simply Forms A-E) in the treatment of patients in need thereof. The invention further provides for processes of making Forms A-E.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1. XRPD pattern of Form A.
Figure 2. DSC/TG data of Form A.
Figure 3. X-ray diffraction pattern of Form B. Figure 4. XRPD pattern of Form B (calculated pattern from single crystal data).
Figure 5. Comparison of the experimental to the calculated XRPD pattern of Form B. The top pattern is an experimental XPRD. The bottom pattern is calculated form single crystal data.
Figure 6. DSC/TG data of Form B.
Figure 7. DSC/TG data of Form C. Figure 8. XRPD pattern of Form C. Figure 9. DSC data of Form D.
Figure 10. XRPD pattern of Form D.
Figure 11. XRPD pattern of Forms A, B. C, and D (top to bottom, respectively).
Figure 12. XRPD pattern of Form E.
DETAILED DKSCRlP fION OF THE INVENTION
Definitions As used herein, the following terms are defined with the following meanings:
"Animal" includes birds and mammals, in one embodiment a mammal, including a dog, cat, cow, horse, goat, sheep, pig or human. In one embodiment the animal is a human. In another embodiment the animal is a male. In another embodiment the animal is a female.
''Diabetes" refers to a heterogeneous group of disorders that share glucose intolerance in common. It refers to disorders in which carbohydrate utilization is reduced and that of lipid and protein enhanced; and may be characterized by hyperglycemia, glycosuria, ketoacidosis, neuropathy or nephropathy, increased hepatic glucose production, insulin
resistance in various tissues, insufficient insulin secretion and enhanced or poorly controlled glucagon secretion from the pancreas.
Several pathogenic processes are involved in the development of diabetes. These range from autoimmune destruction of the beta-cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action. The basis of the abnormalities in carbohydrate, fat, and protein metabolism in diabetes is deficient action of insulin on target tissues. Deficient insulin action results from inadequate insulin secretion and/or diminished tissue responses to insulin at one or more points in the complex pathways of hormone action. Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient.
Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with polyphagia, and blurred vision. The vast majority of cases of diabetes fall into two broad etiopatho genetic categories. In one category, type 1 diabetes, the cause is an absolute deficiency of insulin secretion. Individuals at increased risk of developing this type of diabetes can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islets and by genetic markers. In the other, much more prevalent category, type 2 diabetes, the cause is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. In the latter category, a degree of hyperglycemia sufficient to cause pathologic and functional changes in various target tissues, but without clinical symptoms, may be present for a long period of time before diabetes is detected. During this asymptomatic period, it is possible to demonstrate an abnormality in carbohydrate metabolism by measurement of plasma glucose in the fasting state or after a challenge with an oral glucose load.
Criteria for the diagnosis of diabetes include: 1. Symptoms of diabetes plus casual plasma glucose concentration 200 mg/dl (1 1.1 mmol/1).
Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss; or
2. FPG 126 mg/dl (7.0 mmol/1). Fasting is defined as no caloric intake for at least 8 h; or
3. 2-h postload glucose 200 mg/dl (1 1.1 mmol/1) during an OGTT. The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
Etiologic classification of diabetes mellitus, as embodiments, are as follows: I. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency) A. Immune mediated
B. Idiopathic II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance) ITI. Other specific types
A. Genetic defects of β-cell function
1. Chromosome 12, 1 INF- In (MODY3)
2. Chromosome 7, glucokinase (M0DY2)
3. Chromosome 20, HNF-4λ (MODYl)
4. Chromosome 13, insulin promoter factor- 1 (IPF- 1; MODY4)
5. Chromosome 17, FTNF-IB (MODY5)
6. Chromosome 2, NeuroDl (MODY6)
7. Mitochondrial DNA
8. Others
B. Genetic defects in insulin action
1. Type A insulin resistance
2. Leprechaunism
Rabson-Mendenhall syndrome
4. Lipoatrophic diabetes
5. Others
C. Diseases of the exocrine pancreas
1. Pancreatitis
2. Trauma/pancreatectomy
3. Neoplasia
4. Cystic fibrosis
5. Hemochromatosis
6. Fibrocalculous pancreatopathy
7. Others
D. Endocrinopathies
1. Acromegaly
2. Gushing " s syndrome
Glucagonoma
4. Pheoehromocytoma
5. Hyperthyroidism
6. Somatostalinoma
7. Aldosteronoma
8. Others
E. Drug- or chemical-induced
1. Vacor 2. Pentamidine
3. Nicotinic acid
4. Glucocorticoids
5. Thyroid hormone
6. Diazoxide 7. β-adrenergic agonists
8. Thiazides
9. Dilantin
10. α- Interferon
11. Others F. Infections
1. Congenital rubella
2. Cytomegalovirus
3. Others
G. Uncommon forms of immune-mediated diabetes 1. "Stiff-man" syndrome
2. Anti-insulin receptor antibodies
3. Others
H. Other genetic syndromes sometimes associated with diabetes
1. Down's syndrome 2. Klinefelter' s syndrome
3. Turner ' s syndrome
4. WoI fram ' s syndrome
5. Friedreich's ataxia
6. Iluntington's chorea 7. Laurence-Moon-Biedl syndrome
8. Myotonic dystrophy
9. Porphyria
10. Prader-Willi syndrome
1 1 . Others
IV. Gestational diabetes mellitus (GDM)
"Insulin resistance" is defined clinically as the impaired ability of a known quantity of exogenous or endogenous insulin to increase whole body glucose uptake and utilization.
"Impaired glucose tolerance (IGT)" refers to a condition known to precede the development of overt Type 2 diabetes. It is characterized by abnormal blood glucose excursions following a meal. The current criteria for the diagnosis of IGT are based on 2-h plasma glucose levels post a 75g oral glucose test (144-199 mg/dL). Although variable from population to population studied, IGT progresses to full-blown NIDDM at a rate of 1.5 to
7.3% per year, with a mean of 3-4% per year. Individuals with IGT are believed to have a 6 to 10-fold increased risk in developing Type 2 diabetes. IGT is an independent risk factor for the development of cardiovascular disease.
"'Metabolic Syndrome X" or "The Metabolic Syndrome" is characterized by a group of metabolic risk factors in one person. They include:
• Central obesity (excessive fat tissue in and around the abdomen) • Atherogenic dyslipidemia (blood fat disorders — mainly high triglycerides and low
HDL cholesterol — that foster plaque buildups in artery walls)
• Raised blood pressure (130/85 mniHg or higher)
• Insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar) • Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor [-1J in the blood)
• Proinflammatory state (e.g., elevated high-sensitivity C -reactive protein in the blood) According to the present invention, "Metabolic Syndrome" or "Metabolic Syndrome X" is identified by the presence of three or more of these components: • Central obesity as measured by waist circumference:
Men: Greater than 40 inches Women: Greater than 35 inches
• Fasting blood triglycerides greater than or equal to 150 mg/dL
• Blood HDL cholesterol: • Men: Less than 40 mg/dL
• Women: Less than 50 mg/dL
• Blood pressure greater than or equal to 130/85 mmllg
• Fasting glucose greater than or equal to 110 mg/dL
''Preventing" includes a slowing of the progress or development of a disease before onset or precluding onset of a disease.
'Therapeutically effective amount" means an amount of a compound or a combination of compounds that ameliorates, attenuates or eliminates one or more of the symptoms of a particular disease or condition or prevents, modifies, or delays the onset of one or more of the symptoms of a particular disease or condition.
'"Treating" or "treatment" of a disease includes a slowing of the progress or development of a disease after onset or actually reversing some or all of the disease affects. Treatment also includes palliative treatment.
"Type 1 diabetes" (formerly known as "childhood," "juvenile," "insulin-dependent" diabetes) is a form of diabetes characterized by an absolute deficiency of insulin secretion. Individuals at increased risk of developing this type of diabetes can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islets and by genetic markers. Type 1 diabetes may be caused by immune mediated beta-cell destruction, usually leading to absolute insulin deficiency or may be idiopathic, having no known etiologies.
"Type 2 diabetes" refers to a heterogeneous disorder characterized by impaired insulin secretion by the pancreas and insulin resistance in tissues such as the liver, muscle and adipose tissue. The manifestations of the disease include one or more of the following: impaired glucose tolerance, fasting hyperglycemia, glycosuria, decreased levels of insulin, increased levels of glucagon, increased hepatic glucose output, reduced hepatic glucose uptake and glycogen storage, reduced whole body glucose uptake and utilization, dyslipidemia, fatty liver, ketoacidosis, microvascular diseases such as retinopathy, nephropathy and neuropathy, and macrovascular diseases such as coronary heart disease.
Description:
2-Amino-5-(2,2-dimethyl-propionyl)-4-{2-[5-(N,N'-ethoxyca rbonyl-2-methylprop-2- yl) phosphonamido] furanyl}thiazole (Formula I) is a prodrug of a potent and selective inhibitor of fructose- 1,6-bisphosphatase:
(I)
Other identifying characteristics of the compound of Formula I (herein after, simply Formula I) include the following: Empirical formula: C 24 H 37 N 4 O 7 P S
Molecular mass: 556.62 g/mol
The present invention relates to polymorph Forms A-E.
In one embodiment, the invention provides for a composition consisting of, consisting essentially of or comprising Forms A.
In one embodiment, the invention provides for a composition consisting of, consisting essentially of or comprising Form B. In one embodiment, the invention provides for a composition consisting of, consisting essentially of or comprising Form C.
In one embodiment, the invention provides for a composition consisting of, consisting essentially of or comprising Form D.
In one embodiment, the invention provides for a composition consisting of. consisting essentially of or comprising Form E.
Another embodiment provides for a composition comprising Forms A and B.
Another embodiment provides for a composition comprising Forms A and C.
Another embodiment provides for a composition comprising Forms A and D.
Another embodiment provides for a composition comprising Forms A and E. Another embodiment provides for a composition comprising Forms B and C.
Another embodiment provides for a composition comprising Forms B and D.
Another embodiment provides for a composition comprising Forms B and E.
Another embodiment provides for a composition comprising Forms C and D.
Another embodiment provides for a composition comprising Forms C and E.
Another embodiment provides for a composition comprising Forms D and E.
Another embodiment provides for a composition comprising Formula I, wherein at least 50% of said Formula 1 is Form A.
Another embodiment provides for a composition comprising Formula 1. wherein at least 70% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A.
Another embodiment provides for a composition comprising Formula 1, wherein at least 80% of said Formula 1 is Form A. Another embodiment provides for a composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula 1, wherein at least 50% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein at least 70%) of said Formula I is Form B. Another embodiment provides for a composition comprising Formula 1, wherein at least 75%o of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula 1, wherein at least 90% of said Formula 1 is Form B.
Another embodiment provides for a composition comprising Formula I, wherein at least 95%o of said Formula 1 is Form B.
Another embodiment provides for a composition comprising Formula I, wherein at least 98% of said Formula I is Form B. Another embodiment provides for a composition comprising Formula I, wherein at least 50%) of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein at least 70%o of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein at least 80% of said Formula I is Form C. Another embodiment provides for a composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula 1, wherein at least 95% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula 1, wherein at least 98% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula 1. wherein at least 70% of said Formula I is Form D. Another embodiment provides for a composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein at least 80% of said Formula 1 is Form D.
Another embodiment provides for a composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula 1, wherein at least 95% of said Formula 1 is Form D.
Another embodiment provides for a composition comprising Formula I 5 wherein at least 98%) of said Formula I is Form D. Another embodiment provides for a composition comprising Formula I, wherein at least 50% of said Formula 1 is Form E.
Another embodiment provides for a composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula 1, wherein at least 75% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein at least 80% of said Formula 1 is Form E.
Another embodiment provides for a composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides for a composition comprising Formula I, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula 1 is Form λ.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form A. Another embodiment provides for a composition comprising Formula 1, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I. wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula 1 is Form A.
Another embodiment provides for a composition comprising Formula I. wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form A.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula T, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form B. Another embodiment provides for a composition comprising Formula I, wherein said
Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form B.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form B. Another embodiment provides for a composition comprising Formula I, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E. and wherein less than 2% of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1 % of said Formula I is Form B.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula 1 is Form C.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula T, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula i is Form C. Another embodiment provides for a composition comprising Formula I. wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form C.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form C.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form C. Another embodiment provides for a composition comprising Formula I, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula 1 is Form C.
Another embodiment provides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula I is Form D. Another embodiment provides for a composition comprising Formula I, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula 1, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I. wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form D.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1 % of said Formula I is Form D. Another embodiment provides for a composition comprising Formula T, wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is Form E.
Another embodiment pro\ides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula 1. wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form E. Another embodiment provides for a composition comprising Formula I. wherein said
Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form E.
Another embodiment provides for a composition comprising Formula I, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form E.
In another embodiment, a composition of the present invention is a pharmaceutical composition comprising Form A and a pharmaceutically acceptable excipient.
In another embodiment, a composition of the present invention is a pharmaceutical composition comprising Form B and a pharmaceutically acceptable excipient.
In another embodiment, a composition of the present invention is a pharmaceutical composition comprising Form C and a pharmaceutically acceptable excipient.
In another embodiment, a composition of the present invention is a pharmaceutical composition comprising Form D and a pharmaceutically acceptable excipient. In another embodiment, a composition of the present invention is a pharmaceutical composition comprising Form E and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms A and B and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms A and C and a pharmaceutical) y acceptable cxcipient.
Another embodiment provides for a pharmaceutical composition comprising Forms A and D and a pharmaceutically acceptable excipicnt. Another embodiment provides for a pharmaceutical composition comprising Forms A and E and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms B and C and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms B and D and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms B and E and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms C and D and a pharmaceutically acceptable excipient. Another embodiment provides for a pharmaceutical composition comprising Forms C and E and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Forms D and E and a pharmaceutically acceptable excipient.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 50% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient. wherein at least 70% of said Formula I is Form A. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient. wherein at least 75% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient. wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 90% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 95% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 50% of said Formula I is Form B. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein at least 70% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 75% of said Formula 1 is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 80% of said Formula 1 is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 90% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 95% of said Formula I is Form B. Another embodiment provides for a pharmaceutical composition comprising Formula
1 and a pharmaceutically acceptable excipient, wherein at least 98% of said Formula 1 is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 50% of said Formula 1 is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 70% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 75% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 80% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 90% of said Formula I is Form C. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein at least 95% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 98% of said Formula 1 is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 50% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 70% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 75% of said Formula 1 is Form D. Another embodiment provides for a pharmaceutical composition comprising Formula
1 and a pharmaceutically acceptable excipient, wherein at least 80% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 90% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 95% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 98% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 50% of said Formula 1 is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 70% of said Formula 1 is Form H. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 80% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein at least 90% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 95% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein at least 98% of said Formula I is Form E. Another embodiment provides for a pharmaceutical composition comprising Formula
1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E. and wherein less than 50% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula 1 is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one
crystalline form selected from Forms A-H, and wherein less than 30% of said Formula I is Form λ.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula 1 is Form A. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form A.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula 1 is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form B. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula 1 is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form B. Another embodiment provides for a pharmaceutical composition comprising Formula
1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one
crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form B.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula T comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is
Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient. wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form C. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula 1 is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms λ-E, and wherein less than 2% of said Formula 1 is Form C. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form C.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient. wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form D. Another embodiment provides for a pharmaceutical composition comprising Formula
1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one
crystalline form selected from Forms A-E, and wherein less than 4% of said Formula 1 is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula 1 is Form D,
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 2% of said Formula I is Form D.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form D. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 50% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 40% of said Formula I is Form E,
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 30% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 20% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula 1 and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 10% of said Formula 1 is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 5% of said Formula 1 is Form E. Another embodiment provides for a pharmaceutical composition comprising Formula
I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 4% of said Formula I is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula 1 comprises at least one crystalline form selected from Forms A-E, and wherein less than 3% of said Formula 1 is Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E. and wherein less than 2% of said Formula I is
Form E.
Another embodiment provides for a pharmaceutical composition comprising Formula I and a pharmaceutically acceptable excipient, wherein said Formula I comprises at least one crystalline form selected from Forms A-E, and wherein less than 1% of said Formula I is Form E.
Another embodiment provides for the use of any one or more of Forms A-E for the manufacture of a medicament for the prevention, treatment or reduction of the time to onset of a disease or clinical condition for which an FBPase inhibitor(s) is indicated.
Another embodiment provides for the use of any one or more of Forms A-E in the manufacture of a medicament for the treatment, prevention or reduction of the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels.
Another embodiment provides for a method of treating, preventing or reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E.
Another embodiment provides for a method of for treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels,
the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides for a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels. the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E. Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A. Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogcncsis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 50% of said f ormula I is Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is
Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is
Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is
Form B.
Another embodiment provides a method oO ' treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula 1 is
Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is
Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is
Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method
comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is
Form C,
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is
Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is
Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is
Form C,
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is
Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is
Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula T, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is
Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is
Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is
Form D.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method
comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula 1 is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is
Form E.
Another embodiment provides a method of treating a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is
Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said
Formula I is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1. wherein at least 70% of said
Formula I is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of glυconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form λ.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula i is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula T, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 70% of said
Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said
Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said
Formula 1 is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said
Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels. the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said
Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said
Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels,
the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said
Formula I is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said
Formula I is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said
Formula I is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said
Formula 1 is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 90% of said
Formula 1 is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said
Formula I is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconcogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula 1 is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form C.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said
Formula 1 is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said
Formula I is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said
Formula 1 is Form D.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said
Formula 1 is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said
Formula I is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said
Formula 1 is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels,
the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form R.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels. the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said
Formula I is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said
Formula 1 is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 98% of said
Formula I is Form E.
Another embodiment provides a method of preventing a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said
Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least
50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
70% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
95% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose
levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
70% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula L wherein at least
75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
80% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
90% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
50% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula i, wherein at least
70% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose
levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
90% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
98% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of a disease or condition responsive to inhibition of gluconeogenesis or responsive to lowered blood glucose levels, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form A.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A. Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A. Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B. Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form C.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C, Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C .
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form D, Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form D. Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula 1 is Form E.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form E. Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of treating Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment proλάdes a method of treating Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 99% of said Formula 1 is Form A.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeuticall) effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form B.
Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B. Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula 1 is Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form C. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form C.
Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is
Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C. Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing lype I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I 5 wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of preventing fype I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 95% of said Formula I is Form D. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E. Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E,
Another embodiment provides a method of preventing ' lype I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of Type 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 99% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of Type ϊ diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula i is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 99% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of Type T diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of T>pe 1 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E. Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula i is Form E.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form H.
Another embodiment provides a method of reducing the time to onset of Type I diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form R.
Another embodiment provides a method of treating, preventing or reducing the time to onset of Type 11 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E. Another embodiment provides a method of treating Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B . Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of treating Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating Type 11 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutical!}' effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of treating Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is
Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form E. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form E.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, w r herein at least 98% of said Formula I is Form E. Another embodiment provides a method of treating Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of preventing Type 11 diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of preventing Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form A. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering Io an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a melhod of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form B. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B,
Another embodiment provides a method of preventing Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula T, wherein at least 95% of said Formula I is
Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of preventing Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form C. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 50% of said Formula I is Form E. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1. wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form E.
Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides a method of preventing Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form λ.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form λ.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of inducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least
90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula I is form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of Type Il diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form C. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 99% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Foπn E.
Another embodiment provides a method of reducing the time to onset of Type II diabetes, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an
animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of preventing Metabolic Syndrome X 5 the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a Form C. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπn E. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula
I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula
I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form B. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 50% of said Formula I is Form D. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 80% of said Formula I is Foπn D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I. wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Fonnula 1 is Form D.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form E,
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Foπn E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E. Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of treating Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula
I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula
I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form B.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula
I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula
I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form D. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula 1 is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Foπnula I is Form D.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E. Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form A. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
90% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 50% of said Foπnula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Foπn D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of Metabolic
Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
98% of said Formula I is Form E,
Another embodiment provides a method of reducing the time to onset of Metabolic Syndrome X, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form A. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Foπnula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula
1 is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula
1 is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula
1 is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula
I is Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides a method of treating impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula
I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Foπnula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Foπnula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula
I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides a method of preventing impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form C. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form D. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form E. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 70% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of impaired glucose tolerance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula 1 selected from Forms A-E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is
Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form A. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form B. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form C. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula 1 is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E. Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of treating insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Foπn A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Foπnula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form B. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula 1 is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is
Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form C. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I 5 wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form D. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E. Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is
Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is Form B. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
80% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form C. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least
70% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least
98% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
90% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of insulin resistance, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Foπnula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Foπnula I is Form A. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Foπnula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Foπn C. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Foπn C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1. wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Foπn D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Foπn D.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form D. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is
Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E. Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of treating hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is
Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is
Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutical^ effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 50% of said Foπnula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula 1 is Form D. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a
pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E. Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 50% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Foπn A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form D. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of hyperglycemia, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of treating, preventing or reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula 1 selected from Forms A-E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form A. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Foπnula I is Form B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula
I is Form B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Foπnula I is Form B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form B. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Foπn B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula
I is Foπn B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula T is Foπn B.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula
I is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form C.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount
of a pharmaceutical composition comprising Foπnula I, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula
I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula
I is Form D.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form E. Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula
I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of treating accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form E. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said
Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said
Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said
Formula I is Form D.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form E. Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said
Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Foπn A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 95% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Foπn B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula 1 is Form C. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula 1 is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula L wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Foπn D. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis. the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Foπnula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of accelerated gluconeogenesis, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E. Another embodiment provides a method of treating, preventing or reducing the time to onset of increased or excessive (levels that are greater than normal for a patient having the same medical profile) hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising a crystalline form of Formula I selected from Forms A-E. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form A. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula i is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula i, wherein at least 98% of said
Formula I is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form B. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said
Formula I is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula 1 is Form B. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form B.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said
Formula 1 is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 99% of said Formula 1 is Form C,
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 70% of said Formula 1 is Form D. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective
amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula 1 is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Foπnula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Foπnula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 95% of said Formula I is Form E. Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of treating excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
50% of said Formula I is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula 1 is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula 1 is Form A. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
98% of said Formula I is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
80% of said Formula I is Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 90% of said Formula 1 is Form B .
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
70% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
99% of said Formula I is Form C.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
90% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form D.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least
75% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form E. Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of preventing excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically
effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 70% of said Formula 1 is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form A. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form A.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula 1 is Form B. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a phaπnaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form B. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form B.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula I is Form C. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Foπn C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Foπn C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form C.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Foπnula I, wherein at least 50% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 80% of said Formula 1 is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 90% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 98% of said Formula I is Form D. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula I is Form D.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 50% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a
therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 70% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 75% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 80% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula 1, wherein at least 90% of said Formula I is Form E. Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 95% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 98% of said Formula I is Form E.
Another embodiment provides a method of reducing the time to onset of excessive hepatic glucose output, the method comprising the step of administering to an animal a therapeutically effective amount of a pharmaceutical composition comprising Formula I, wherein at least 99% of said Formula 1 is Form E.
In one embodiment, compounds of the invention are administered in a total daily dose of 0.01 to 2500 mg. In another embodiment the range is about 1 mg to about 1000 mg. In another embodiment the range is about 1 mg to about 500 mg. In another embodiment the range is about 10 mg to about 500 mg. hi another embodiment the range is about 10 mg to about 250 mg. In another embodiment the range is about 50 mg to about 250 mg. In another embodiment the range is about 50 mg to about 150 mg. In another embodiment the range is about 50 mg to about 100 mg. In another embodiment the range is about 10 mg to about 150 mg. The dose may be administered in as many divided doses as is convenient.
One embodiment of the invention encompasses a unit dosage form which comprises a pharmaceutically acceptable composition comprising a crystalline form of the present invention and one or more pharmaceutically acceptable carrier excipients or diluents.
In another embodiment, compounds of the invention are administered in a unit dose of a range between 0.01 to 1000 mg. In another embodiment the range is about 0.1 mg to about
500 mg. In one aspect the range is about 0.1 mg to about 100 mg. In another embodiment the range is about 1 mg to about 1000 mg. In one embodiment the range is about 1 mg to about 500 mg. In another embodiment the range is about 1 mg to about 100 mg. In one embodiment the range is about 1 mg to about 10 mg. In one embodiment the range is about 10 mg to about 1000 mg. In one embodiment the range is about 10 mg to about 500 mg. In one embodiment the range is about 10 mg to about 150 mg. In one embodiment the range is about 10 mg to about 100 mg. In one embodiment, the unit dose is about 10 mg. In one embodiment, the unit dose is about 25 mg. In one embodiment, the unit dose is about 50 mg. In one embodiment, the unit dose is about 75 mg. In one embodiment, the unit dose is about 100 mg. In one embodiment, the unit dose is about 150 mg. In one embodiment, the unit dose is about 200 mg. In one embodiment, the unit dose is about 250 mg. In one embodiment, the unit dose is about 300 mg. In one embodiment, the unit dose is about 400 mg. In one embodiment, the unit dose is about 500 mg. In one embodiment, the unit dose is 600 mg. In one embodiment, the unit dose is 700 mg. In one embodiment, the unit dose is about 800 mg. In one embodiment, the unit dose is about 900 mg. In one embodiment, the unit dose is about 1000 mg.
In one embodiment the compound is administered QD (once a day). In another embodiment the compound is administered BID (twice a day). In another embodiment the compound is administered TID (three times a day). In another embodiment the compound is administered QID (four times a day). In another embodiment the compound is administered before a meal. In another embodiment the compound is administered after a meal. In another embodiment the compound is administered in the morning hours or upon awakening. In another embodiment the compound is administered in the evening hours or at bedtime.
Pharmaceutically acceptable compositions or medicaments can be administered by various means. One embodiment relates to the administration of a pharmaceutically acceptable composition of the present invention by controlled- or delayed-release means. Controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled release counterparts.
A variety of known controlled- or extended-release dosage forms, formulations, and devices can be adapted for use with the crystalline forms of the invention. Examples include, but are not limited to, those described in U.S. Pat. Nos.: 3,845,770; 3,916,899; 3,536,809;
3,598, 123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5, 639,476; 5,354,556; 5,733,566; and 6,365,185; each of which is incorporated herein by reference.
These dosage forms can be used to provide slow or controlled- release of one or more active ingredients using, for example, hydroxypropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems (such as OROS, Alza Corporation, Mountain View, Calif. USA), multilayer coatings, microparticles, liposomes, or microspheres or a combination thereof to provide the desired release profile in varying proportions. Additionally, ion exchange materials can be used to prepare immobilized, adsorbed co- crystals and thus effect controlled delivery of the drug. Examples of specific anion exchangers include, but are not limited to, Duolite A568 and Duolite AP143 (Rohm & Haas, Spring House, PA, USA). One embodiment of the invention encompasses a unit dosage formulated for controlled-release which comprises a pharmaceutically acceptable composition comprising a crystalline form of the present invention and one or more pharmaceutically acceptable carrier excipients or diluents. In one embodiment the pharmaceutical composition, medicament or dosage forms is formulated for controlled-release. In another embodiment, the dosage form utilizes an osmotic drug delivery system.
A particular and well-known osmotic drag delivery system is referred to as OROS (Alza Corporation, Mountain View, Calif. USA). This technology can readily be adapted for the delivery of compounds and compositions of the invention. Various aspects of the technology are disclosed in U.S. Pat. Nos. 6, 375, 978; 6,368,626 ; 6,342,249; 6,333,050; 6,287,295; 6, 283,953; 6,270,787; 6,245,357; and 6,132,420; each of which is incorporated herein by reference.
Conventional OROS oral dosage forms are made by compressing a drug powder (e.g. a crystalline form selected from Forms A-E) into a hard tablet, coating the tablet with cellulose derivatives to form a semi-permeable membrane, and then drilling an orifice in the coating (e.g., with a laser). Kim, Cherug-ju, Controlled Release Dosage Form Design, 231- 238 (Technomic Publishing, Lancaster, PA: 2000).
A specific dosage form of the invention comprises: a wall defining a cavity, the wall having an exit orifice formed or formable therein and at least a portion of the wall being semipermeable; an expandable layer located within the cavity remote from the exit orifice
and in fluid communication with the semipermeable portion of the wall; a dry or substantially dry state drug layer located within the cavity adjacent to the exit orifice and in direct or indirect contacting relationship with the expandable layer; and a flow-promoting layer interposed between the inner surface of the wall and at least the external surface of the drug layer located within the cavity, wherein the drug layer comprises a crystalline form selected from Forms A-E. See U.S. Pat. No. 6,368,626, the entirety of which is incorporated herein by reference.
Another specific dosage form of the invention comprises: a wall defining a cavity, the wall having an exit orifice formed or formable therein and at least a portion of the wall being semipermeable; an expandable layer located within the cavity remote from the exit orifice and in fluid communication with the semipermeable portion of the wall; a drug layer located within the cavity adjacent the exit orifice and in direct or indirect contacting relationship with the expandable layer; the drag layer comprising a liquid, active agent formulation absorbed in porous particles, the porous particles being adapted to resist compaction forces sufficient to form a compacted drug layer without significant exudation of the liquid, active agent formulation, the dosage form optionally having a placebo layer between the exit orifice and the drug layer, wherein the active agent formulation comprises a crystalline form selected from Forms A-E. See U. S. Pat. No. 6,342,249, the entirety of which is incorporated herein by reference. In another embodiment, a pharmaceutical composition or medicament comprising a crystalline form selected from Forms A-E is administered transdermally. Such a transdermal (TD) delivery can avoid first-pass metabolism. Additionally, a "pill-and-patch" strategy can be taken, where only a fraction of the daily dose is delivered through the skin to generate basal systemic levels, onto which oral therapy is added. Excipients employed in pharmaceutical compositions and medicaments of the present invention can be solids, semi-solids, liquids or combinations thereof. Preferably, excipients are solids. Compositions and medicaments of the invention containing excipients can be prepared by known technique of pharmacy that comprises admixing an excipient with an API or therapeutic agent (e.g, a crystalline form selected from Forms A-E). A pharmaceutical composition or medicament of the invention contains a desired amount of a crystalline form selected from Forms A-E per dose unit and, if intended for oral administration, can be in the form, for example, of a tablet, a caplet, a pill, a hard or soft capsule, a lozenge, a cachet, a dispensable powder, granules, a suspension, an elixir, a dispersion, a liquid, or any other form reasonably adapted for such administration. If intended for parenteral administration, it can
be in the form, for example, of a solution for intravenous, intramuscular or subcutaneous injection or transdermal patch. If intended for rectal administration, it can be in the form, for example, of a suppository. Presently preferred are oral dosage forms that are discrete dose units each containing a predetermined amount of the API, such as tablets or capsules. Pharmaceutical compositions and medicaments of the invention optionally comprise one or more pharmaceutically acceptable carriers or diluents as excipients.
Suitable carriers or diluents illustratively include, but are not limited to, either individually or in combination, lactose, including anhydrous lactose and lactose monohydrate; starches, including directly compressible starch and hydrolyzed starches (e.g., Celutab and Emdex); mannitol; sorbitol; xylitol; dextrose (e.g., Cerelose 2000) and dextrose monohydrate; dibasic calcium phosphate dihydrate; sucrose-based diluents; confectioner's sugar; monobasic calcium sulfate monohydrate; calcium sulfate dihydrate; granular calcium lactate trihydrate; dextrates; inositol; hydrolyzed cereal solids; amylose; celluloses including microcrystalline cellulose, food grade sources of alpha- and amorphous cellulose (e.g., RexcelJ), powdered cellulose, hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC); calcium carbonate; glycine; bentonite; block copolymers; polyvinylpyrrolidone; and the like. Such carriers or diluents, if present, constitute in total about 5% to about 99%, preferably about 10% to about 85%, and more preferably about 20% to about 80%, of the total weight of the composition. The carrier, carriers, diluent, or diluents selected preferably exhibit suitable flow properties and, where tablets are desired, compressibility.
Lactose, mannitol, dibasic sodium phosphate, and microcrystalline cellulose (particularly Avicel PH microcrystalline cellulose such as Avicel PH 101), either individually or in combination, are examples of diluents. These diluents are chemically compatible with APIs. The use of extragranular microcrystalline cellulose (that is, microcrystalline cellulose added to a granulated composition) can be used to improve hardness (for tablets) and/or disintegration time. Lactose, especially lactose monohydrate, is particularly preferred. Lactose typically provides compositions having suitable release rates of APIs, stability, pre- compression flowability, and/or drying properties at a relatively low diluent cost. It provides a high density substrate that aids densifϊcation during granulation (where wet granulation is employed) and therefore improves blend flow properties and tablet properties.
Pharmaceutical compositions and medicaments of the invention optionally comprise one or more pharmaceutically acceptable disintegrants as excipients, particularly for tablet formulations. Suitable disintegrants include, but are not limited to, either individually or in
combination, starches, including sodium starch glycolate (e.g., Explotab of Pen West) and pregelatinized corn starches (e.g., National 1551 of National Starch and Chemical Company, National 1550, and Colocorn 1500), clays (e.g., Veegum HV of R.T. Vanderbilt), celluloses such as purified cellulose, micro crystalline cellulose, methylcellulose, carboxymethylcellulose and sodium carboxymethylcellulose, croscarmellose sodium (e.g.,
Ac-Di-SoI of FMC), alginates, crospovidone, and gums such as agar, guar, locust bean, karaya, pectin and tragacanth gums.
Disintegrants may be added at any suitable step during the preparation of the composition, particularly prior to granulation or during a lubrication step prior to compression. Such disintegrants, if present, constitute in total about 0.2% to about 30%, preferably about 0. 2% to about 10%, and more preferably about 0.2% to about 5%, of the total weight of the composition.
Croscarmellose sodium is a preferred disintegrant for tablet or capsule disintegration, and, if present, preferably constitutes about 0.2% to about 10%, more preferably about 0.2% to about 7%, and still more preferably about 0.2% to about 5%, of the total weight of the composition. Croscarmellose sodium confers superior intragranular disintegration capabilities to granulated pharmaceutical compositions and medicaments of the present invention.
Pharmaceutical compositions and medicaments of the invention optionally comprise one or more pharmaceutically acceptable binding agents or adhesives as excipients, particularly for tablet formulations. Such binding agents and adhesives preferably impart sufficient cohesion to the powder being tableted to allow for normal processing operations such as sizing, lubrication, compression and packaging, but still allow the tablet to disintegrate and the composition to be absorbed upon ingestion. Such binding agents may also prevent or inhibit crystallization or recrystallization of an API of the present invention once the compound has been dissolved in a solution. Suitable binding agents and adhesives include, but are not limited to, either individually or in combination, acacia; tragacanth; sucrose; gelatin; glucose; starches such as, but not limited to, pregelatinized starches (e.g., National 1511 and National 1500); celluloses such as, but not limited to, methylcellulose and carmellose sodium (e.g., Tylose); alginic acid and salts of alginic acid; magnesium aluminum silicate; PEG; guar gum; polysaccharide acids; bentonites; povidone, for example povidone K-15, K-30 and K-29/32; polymethacrylates; HPMC; hydroxypropylcellulose (e.g., Klucel of Aqualon), and ethylcellulose (e. g., Ethocel of the Dow Chemical Company). Such binding agents and/or adhesives, if present, constitute in total about 0.5% to about 25%, preferably
about 0.75% to about 15%, and more preferably about 1% to about 10%, of the total weight of the pharmaceutical composition or medicament.
Many of the binding agents are polymers comprising amide, ester, ether, alcohol or ketone groups and, as such, are preferably included in pharmaceutical compositions and medicaments of the present invention. Polyvinylpyrrolidones such as povidone K-30 are especially preferred. Polymeric binding agents can have varying molecular weight, degrees of crosslinking, and grades of polymer. Polymeric binding agents can also be copolymers, such as block co-polymers that contain mixtures of ethylene oxide and propylene oxide units. Variation in these units' ratios in a given polymer affects properties and performance. Examples of block co- polymers with varying compositions of block units are Poloxamer 188 and Poloxamer 237 (BASE Corporation).
Pharmaceutical compositions and medicaments of the invention optionally comprise one or more pharmaceutically acceptable wetting agents as excipients. Such wetting agents are preferably selected to maintain the API in close association with water, a condition that is believed to improve bioavailability of the composition.
Non-limiting examples of surfactants that can be used as wetting agents in pharmaceutical compositions and medicaments of the invention include quaternary ammonium compounds, for example benzalkonium chloride, benzethonium chloride and cctylpyridinium chloride, dioctyl sodium sulfosuccinate, polyoxyethylene alkylphenyl ethers, for example nonoxynol 9, nonoxynol 10, and octoxynol 9, poloxamers (polyoxyethylene and polyoxypropylene block copolymers), polyoxyethylene fatty acid glycerides and oils, for example polyoxyethylene (8) caprylic/capric mono- and diglycerides (e.g., Labrasol ^ of Gattefosse), polyoxyethylene (35) castor oil and polyoxyethylene (40) hydrogenated castor oil; polyoxyethylene alkyl ethers, for example polyoxyethylene (20) cetostearyl ether, polyoxyethylene fatty acid esters, for example polyoxyethylene (40) stearate, polyoxyethylene sorbitan esters, for example polysorbate 20 and polysorbate 80 (e.g., Tween 80 of ICI), propylene glycol fatty acid esters, for example propylene glycol laurate (e.g., Lauroglycol of Gattefosse), sodium lauryl sulfate, fatty acids and salts thereof, for example oleic acid, sodium oleate and triethanolamine oleate, glyceryl fatty acid esters, for example glyceryl monostearate, sorbitan esters, for example sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate and sorbitan monostearate, tyloxapol, and mixtures thereof. Such wetting agents, if present, normally constitute in total about 0.25% to about 15%, preferably about 0.4% to about 10%, and more preferably about 0.5% to about 5%, of the total weight of the pharmaceutical composition or medicament.
Wetting agents that are anionic surfactants are preferred. Sodium lauryl sulfate is a particularly preferred wetting agent. Sodium lauryl sulfate, if present, normally constitutes about 0.25% to about 7%, more preferably about 0. 4% to about 4%, and still more preferably about 0.5% to about 2%, of the total weight of the pharmaceutical composition or medicament.
Pharmaceutical compositions and medicaments of the invention optionally comprise one or more pharmaceutically acceptable lubricants (including anti-adherents and/or glidants) as excipients. Suitable lubricants include, but are not limited to, either individually or in combination, glyceryl behapate (e.g., Compritol 888 of Gattefosse); stearic acid and salts thereof, including magnesium, calcium and sodium stearates; hydrogenated vegetable oils (e.g., Sterotex of Abitec); colloidal silica; talc; waxes; boric acid; sodium benzoate; sodium acetate; sodium fumarate; sodium chloride; DL-leucine; PEG (e.g., Carbowax 4000 and Carbowax 6000 of the Dow Chemical Company); sodium oleate; sodium lauryl sulfate; and magnesium lauryl sulfate. Such lubricants, if present, normally constitute in total about 0. 1% to about 10%, preferably about 0.2% to about 8%, and more preferably about 0.25% to about
5%, of the total weight of the pharmaceutical composition or medicament. Magnesium stearate is a preferred lubricant used, for example, to reduce friction between the equipment and granulated mixture during compression of tablet formulations.
Suitable anti-adherents include, but are not limited to, talc, cornstarch, DL- leucine, sodium lauryl sulfate and metallic stearates. Talc is a preferred anti-adherent or glidant used, for example, to reduce formulation sticking to equipment surfaces and also to reduce static in the blend. Talc, if present, constitutes about 0.1% to about 10%, more preferably about 0.25% to about 5%, and still more preferably about 0.5% to about 2%, of the total weight of the pharmaceutical composition or medicament. Glidants can be used to promote powder flow of a solid formulation. Suitable glidants include, but are not limited to, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate, powdered cellulose and magnesium trisilicate. Colloidal silicon dioxide is particularly preferred.
Other excipients such as colorants, flavors and sweeteners are known in the pharmaceutical art and can be used in pharmaceutical compositions and medicaments of the present invention. Tablets can be coated, for example with an enteric coating, or uncoated. Compositions of the invention can further comprise, for example, buffering agents.
Optionally, one or more effervescent agents can be used as disintegrants and/or to enhance organoleptic properties of pharmaceutical compositions and medicaments of the invention. When present in pharmaceutical compositions and medicaments of the invention to
promote dosage form disintegration, one or more effervescent agents are preferably present in a total amount of about 30% to about 75%, and preferably about 45% to about 70%, for example about 60%, by weight of the pharmaceutical composition or medicament.
According to a particularly preferred embodiment of the invention, an effervescent agent, present in a solid dosage form in an amount less than that effective to promote disintegration of the dosage form, provides improved dispersion of the API in an aqueous medium. Without being bound by theory, it is believed that the effervescent agent is effective to accelerate dispersion of the API, from the dosage Forms A-En the gastrointestinal tract, thereby further enhancing absorption and rapid onset of therapeutic effect. When present in a pharmaceutical composition or medicament of the invention to promote intragastrointestinal dispersion but not to enhance disintegration, an effervescent agent is preferably present in an amount of about 1% to about 20%, more preferably about 2.5% to about 15%, and still more preferably about 5% to about 10%, by weight of the pharmaceutical composition or medicament. An "effervescent agent" herein is an agent comprising one or more compounds which, acting together or individually, evolve a gas on contact with water. The gas evolved is generally oxygen or, most commonly, carbon dioxide. Preferred effervescent agents comprise an acid and a base that react in the presence of water to generate carbon dioxide gas. Preferably, the base comprises an alkali metal or alkaline earth metal carbonate or bicarbonate and the acid comprises an aliphatic carboxylic acid.
Non-limiting examples of suitable bases as components of effervescent agents useful in the invention include carbonate salts (e.g., calcium carbonate), bicarbonate salts (e.g., sodium bicarbonate), sesquicarbonate salts, and mixtures thereof. Calcium carbonate is a preferred base. Non-limiting examples of suitable acids as components of effervescent agents and/or solid acids useful in the invention include citric acid, tartaric acid (as D-, L-, or D/L-tartaric acid), malic acid, maleic acid, fumaric acid, adipic acid, succinic acid, acid anhydrides of such acids, acid salts of such acids, and mixtures thereof. Citric acid is a preferred acid.
In a preferred embodiment of the invention, where the effervescent agent comprises an acid and a base, the weight ratio of the acid to the base is about 1 : 100 to about 100:1, more preferably about 1:50 to about 50:1, and still more preferably about 1 :10 to about 10:1. In a further preferred embodiment of the invention, where the effervescent agent comprises an acid and a base, the ratio of the acid to the base is approximately stoichiometric.
Excipients which solubilize salts of APIs may have both hydrophilic and hydrophobic regions, or are preferably amphiphilic or have amphiphilic regions. One type of amphiphilic or partially- amphiphilic excipient comprises an amphiphilic polymer or is an amphiphilic polymer. A specific amphiphilic polymer is a polyalkylene glycol, which is commonly comprised of ethylene glycol and/or propylene glycol subunits. Such polyalkylene glycols can be esterified at their termini by a carboxylic acid, ester, acid anhyride or other suitable moiety. Examples of such excipients include poloxamers (symmetric block copolymers of ethylene glycol and propylene glycol; e.g., poloxamer 237), polyalkyene glycolated esters of tocopherol (including esters formed from a di- or multi-functional carboxylic acid; e.g., d- alpha-tocopherol polyethylene glycol- 1000 succinate), and macrogolglycerides (formed by alcoholysis of an oil and esterification of a polyalkylene glycol to produce a mixture of mono-, di- and tri-glycerides and mono- and all- esters; e.g., stearoyl macrogol-32 glycerides). Such pharmaceutical compositions and medicaments are advantageously administered orally. Solid dosage forms of the invention can be prepared by any suitable process, not limited to processes described herein. An illustrative process comprises (a) a step of blending a compound of the invention with one or more excipients to form a blend, and (b) a step of tableting or encapsulating the blend to form tablets or capsules, respectively.
In a preferred process, solid dosage forms are prepared by a process comprising (a) a step of blending a compound of the invention with one or more excipients to form a blend, (b) a step of granulating the blend to form a granulate, and (c) a step of tableting or encapsulating the blend to form tablets or capsules respectively. Step (b) can be accomplished by any dry or wet granulation technique known in the art, but is preferably a dry granulation step. A compound of the present invention is advantageously granulated to form particles of about 1 micrometer to about 100 micrometer, about 5 micrometer to about 50 micrometer, or about 10 micrometer to about 25 micrometer. One or more diluents, one or more disintegrants and one or more binding agents are preferably added, for example in the blending step, a wetting agent can optionally be added, for example in the granulating step, and one or more disintegrants are preferably added after granulating but before tableting or encapsulating. A lubricant is preferably added before tableting. Blending and granulating can be performed independently under low or high shear. A process is preferably selected that forms a granulate that is uniForms A-En API content, that readily disintegrates, that flows with sufficient ease so that weight variation can be reliably controlled during capsule filling or
tableting, and that is dense enough in bulk so that a batch can be processed in the selected equipment and individual doses fit into the specified capsules or tablet dies.
In an alternative embodiment, solid dosage forms are prepared by a process that includes a spray drying step, wherein the API is suspended with one or more excipients in one or more sprayable liquids, preferably a non-protic (e.g., non-aqueous or non-alcoholic) sprayable liquid, and then is rapidly spray dried over a current of warm air.
A granulate or spray dried powder resulting from any of the above illustrative processes can be compressed or molded to prepare tablets or encapsulated to prepare capsules. Conventional tableting and encapsulation techniques known in the art can be employed. Where coated tablets are desired, conventional coating techniques are suitable.
Excipients for tablet compositions of the invention are preferably selected to provide a disintegration time of less than about 30 minutes, preferably about 25 minutes or less, more preferably about 20 minutes or less, and still more preferably about 15 minutes or less, in a standard disintegration assay. In another embodiment the invention provides for a pharmaceutical composition or medicament comprising a first API that is a crystalline form selected from Forms A-E and a second API, wherein said first API and second API are not the same API.
EXAMPLES
Chemical synthesis of compound
Preparation of 2-amino-5-(2,2-dimethylpropionyl)-4- {[5-(N,N'-(2-ethoxy- carbonylprop-2-yl)phosphonamido]furan-2-yl}thiazole:
Step A
A solution of 2-furoic acid (1 mmole) in THF was added to a THF solution of LDA (lithium diisopropylamide, 2 mmole) at -78 0 C and the resulting solution was stirred at - 78 0 C. After Ih the reaction mixture was treated with diethyl chlorophosphate (1.2 mmole), stirred at - 78 0 C for 1 h and at 25 0 C for 12 h. The reaction mixture was quenched with saturated ammonium chloride. Extraction and chromatography gave 5-diethylphosphono-2-furoic acid as a yellow solid.
Step B
A solution of 5-diethylphosphono-2-furoic acid (1 mmole) and O-m ethyl -N-methylhydroxylamide HCl salt (1.3 mmole) in DMF was treated with triethylamine (2.2 mmole) and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, 1.2 mmole) at 25 0 C. After 12 h, the reaction was subject to extraction and chromatography to give 5-diethylphosphono-
2-(N-methyl-N-methoxy)furancarboxamide as a solid.
Step C
A solution of pinacolone (1.4 mmole) in THF was cooled to -78 0 C and treated with n-BuLi (1.5 mmole). After 1 h, to the reaction was added a solution of 5-diethylphosphono-2-(N-methyl-N-methoxy)furancarboxamide (1 mmole) in THF and stirred at -78 0 C for 1 h and at 25 0 C for 12 h. The reaction was quenched with saturated ammonium chloride and subjected to extraction and chromatography to give 5-diethylphosphono-2-[l-(4,4-dimethyl-l,3-dioxo)pentyl]furan as an oil.
Step D
A solution of 5-diethylphosphono-2-[l-(4,4-dimethyl-l,3-dioxo)pentyl]furan (1 mmole) in carbon tetrachloride and ethanol was treated with copper (II) bromide (1.6 mmole) at 25 0 C. After heating at 70 0 C for 3 h the reaction was cooled to 25 0 C and subjected to extraction and chromatography to give 5-diethylphosphono-2-[l-(2-bromo-4,4-dimethyl-l ,3- dioxo)pentyl]furan as an oil.
Step E
A solution of 5-diethylphosphono-2-[l-(2-bromo-4,4-dimethyl-l ,3-dioxo)- pentyljfuran (1 mmole) in ethyl acetate and ethanol was treated with thiourea (1.8 mmole) at 25 0 C. After heating at 70 0 C for 3 h the reaction was cooled to 25 0 C and subjected to extraction and chromatography to give
{5-[2-Amino-5-(2,2-dimethyl-propionyl)-thiazol-4-yl]-fura n-2-yl}-phosphonic acid diethyl ester as a solid.
Step F
A solution of {5-[2-amino-5-(2,2-dimethyl-propionyl)thiazol- 4-yl]furan-2-yl}phosphonic acid diethyl ester (1 mmole) in methylene chloride was treated
with TMSBr (10 mmole) at 25 0 C. After 12 h the reaction was evaporated to dryness and the residue was suspended in acetone-water to give a yellow solid. The solid was collected via filtration and dried under vacuum to give {5-[2-amino-5-(2,2-dimethyl-propionyl)thiazol- 4-y]]-furan-2-yl}phosphonic acid (Formula II) as a solid. Mp > 220 0 C. Anal, calcd. for Ci 2 H 15 N 2 O 5 PS: C: 43.64; H: 4.58; N: 8.48. Found: C: 43.47; H: 4.64: N: 8.55.
(H)
Step G.
A solution of {5-[2-amino-5-(2,2-dimethyl-propionyl)thiazol-4-yl]furan-2-y l}phosphonic acid (1 mmole), DMF (1.2 mmole) and oxalyl chloride (4 mmole) in 1 ,2-dichloroeιhane was heated at 50 0 C for 2 h. The reaction solution was evaporated to dryness and the residue was redissolved in 1,2-dichloroethane. After cooling to O 0 C, 2-methylalanine ethyl ester (3.5 mmole) and N,N-diethylisopropylamine (3.5 mmole) were added. After stirring at 25 0 C for
12 h, the reaction was subjected to extraction and chromatography to give
2-(dimethylaminomethyleneamino)-5-(2,2- dimethylpropionyl)-4-{2-[5-(N,N'-2-ethoxycarbonylprop-2-yl)- phosphon-amido]- furanyl}thiazole.
Step H.
A solution of 2-(dimethylamino-methyleneamino)-5-(2,2- dimethylpropionyl)-4-{[5-(N,N'-2-ethoxycarbonylprop-2-yl)pho sphonamido]furan-2- yl}thiazole (1 mmole) in acetic acid and isopropanol was heated to 85 0 C. After 12h the reaction was subjected to extraction and chromatography to give 2-amino-5-(2,2- dimethylpropionyl)-4- { [ 5 - (N,N ' - (2- ethoxy- carbonylprop-2-yl)phosphonamido]furan-2-yl}thiazole (Formula I) as a yellow solid. Anal.
CaICcI fOr C 24 H 37 N 4 O 7 PS: C: 51.79; H: 6.70; N: 10.07. Found: C: 51.39; H: 6.51; N: 10.26.
(I)
O Il H-P(OEt) 2
[(C 6 H 5 J 3 P] 4 Pd
Scheme 1
Formula I can also be prepared by the synthetic scheme shown in Scheme 1. 5-Bromo-2- furoic acid is converted to the acid chloride 1 with oxalyl chloride or other suitable reagents. The acid chloride 1 is condensed with the anion of pinacolone to form diketone 2. The bromofuran diketone 2 is phosphonylated with diethyl phosphate to diketone 3 using a suitable transition metal catalyst such as tetrakis(triphenylphosphine)palladium (0). The diketone 3 is halogenated with a suitable reagent such as bromine or sulfuryl chloride to
provide halodiketone 4. The dialkylphosphonate is condensed with thiourea to provide thiazole 5. The dialkylphosphonate functionality of 5 is deprotected using a suitable reagent such as trimethylsilyl halide to provide the phosphonic acid 6. The phosphonic acid 6 is converted to an amidine protected phosphonodichloridate using sutable reagents such as oxalyl chloride with a dialkylformamide, or thionyl chloride. The phosphonodichloridate is treated with 2-methyl alanine ethyl ester hydrochloride or the free base, and a suitable acid- scavenging base such as triethylamine or diisopropylethylamine (DIPEA), to provide the crude bisamidate. The arnidine protecting group is removed with a suitable reagent such as acetic acid in ethanol to form the product Formula I.
Analytical Methods
Unless specifically set forth in an Example to the contrary, analytical methods were carried out as follows. See Examples for specific analytical methods used to characterize a specific form. X -ray powder diffraction (XRPD) analysis was performed using a Shimadzu XRD-
6000 X-Ray powder diffractometer using Cu Ka radiation. The instrument is equipped with a fine focus X-ray tube. The tube voltage and amperage were set to 4OkV and 4OmA, respectively. The divergence and scattering slits were set at 1° and the receiving slit was set at 0.15 mm. Diffraction radiation was detected by NaI scintillation detector. A theta - two theta continuous scan at 3° / minute (0.4 second / 0.02° step) from 2.4 to 40° 2θ was used. A silicon standard was analyzed to check the instrument alignment. Data were collected and analyzed using XRD / 6000 v.4.1.
X-ray powder diffraction (XRPD) analyses were also performed using an Inel XRG- 3000 diffractometer equipped with a CPS (Curved Position Sensitive) detector with a 20 range of 120°. Real time data were collected using a Cu-Ka radiation starting at approximately 4 ° 20 at a resolution of 0.03 ° 2θ. The tube voltage and amperage were set to 40 kV and 30 mA, respectively. The monochromator slit was set at 5 mm by 160μm. The pattern is displayed from 2.5-40 ° 2θ. Samples were prepared for analysis by packing them into thin-walled glass capillaries. Each capillary was mounted onto a goniometer head that is motorized to permit spinning of the capillary during data acquisition. The samples were analyzed for 2 min. Instrument calibration was performed using a silicon reference standard. The experimental XRPF pattern was collected at SSCI, Inc. using the as-received sample according to cGMP specifications.
Variable-temperature XRPD (VT-XRPD) was performed on a Shimadzu XRD-6000 X-ray powder diffractometer equipped with an Anton Paar HTK 1200 high temperature stage. The sample was packed in a ceramic holder and analyzed from 2.5 to 40° 2θ at 3 7min (0.4sec/0/02° step). A silicon standard was analyzed to check the instrument alignment. Differential scanning calorimetery (DSC) was performed using a TA instrument differential scanning calorimeter 2920. Each sample was placed into an aluminum DSC pan, and the weight accurately recorded. The pan was then covered with a lid. Each sample was equilibrated at 25 0 C and heated under a nitrogen purge at a rate of 10 0 C / minute, upto a final temperature of 350 0 C. Indium metal was used as the calibration standard. Reported temperatures are at the transition maxima.
Cyclic differential scanning calorimetry (Cyclic DSC) was performed using a TA Instruments 2920 differential scanning calorimeter. The sample was placted into an aluminum DSC pan and the weight accurately recorded. The pan was covered with a lid and then crimped. The method was as follows: 1. Equilibrate at 25.00 0 C,
2. Ramp 5 o C/min to 175 0 C,
3. Isothermal at 175 0 C for 5 min,
4. Equilibrate at 25 0 C,
5. Ramp 5 °C/min to 225 0 C. Indium metal was used as the calibration standard. Reported temperature is at the transition maxima.
Thermogravimetric (TG) analyses were performed using a TA instruments 2050 thermogravemetric analyzer. The sample was placed in an aluminum sample pan, into the TG furnace. The sample was first equilibrated at 25 0 C, than heated under nitrogen at 10 0 C / min, up to a final temperature of 350 0 C. Nickel and ALUMEL™ were used as the calibration standards.
Hot-stage microscopy was peformed using a Linkman hot-stage (model FTIR 600) mounted on a Leica DM microscope. Samples were observed using a 2Ox objective with a lambda place and crossed polarizers. Samples were placed on a coverslip. Another coverslip was then placed over the sample. Each sample was visually observe as the stage was heated.
The hot-stage was calibrated using USP melting point standards.
Moisture sorption / desorption data were collected on a VTI SGA/100 Vapor Sorption Analyzer using VTI Flow System Software / Step Isotherm Experiment. Sorption and
Desorption data were collected over a range of 5% to 95% relative humidity (RH) at 10% RH intervals under a nitrogen purge. Samples were not dried prior to analysis. Equilibrium criteria used for analysis was less than 0.0100% weight change in 5 minutes, with a maximum equilibration time of 3 hours if the weight criterion was not met. Data were not collected for the initial moisture content of the samples. NaCl and PVP were used as calibration standards.
Optical microscopy was performed using a Wolfe Microscope. Samples were observed at magnification of 40x using cross-polarizers.
Example 1. Form A:
Crystalline Form A was made by adding tetrahyrofuran (THF) to 2-Amino-5-(2,2- dimethyl-propionyl)-4-{2-[5-(N,N'-ethoxycarbonyl-2-methylpro p-2-yl) phosphonamido] furanyl}thiazole [1.5:1 (vol:wt) THF:Formula I]. The solution (about 20 0 C) was stirred and ambient temperature n-heptane was added rapidly [5:1 (vol:wt) heptane: Formula I]. The filter cake was washed with n-heptane and dried in a vacuum oven at 40 0 C.
A representative XRPD pattern (Shimadzu XRD-6000) of Form A is shown in Figure 1. The peaks in the list below are selected from XRPD images that represent clear signals above the noise level. Peak positions can be +/- 0.2 °2theta.
* weak signals.
TG analysis of Form A sample demonstrated an insignificant weight loss indicating the solid is anhydrous and unsolvated (Figure II). DSC data revealed a single major endothermic transition with a peak maximum at about 156 0 C and a minor endothermic transition at about 170 0 C (Figure T), Hot-stage microscopy analysis showed a melt at about 154 0 C, followed by a recrystallization and a second melt of the recrystallazation phase at about 169 0 C.
Automated moisture sorption/desorption analysis of Form A sample exhibited insignificant weight gain of 0.22% at 95% RH. Upon desorption to 5% RH, the sample returned to its initial mass.
Example 2. Form B:
Crystalline Form B was made by adding methanol (can also be made with ethanol) to 2-Amino-5-(2,2-dimethyl-propionyl)-4- (2-[5-(N,N'-ethoxycarbonyl-2-methylprop-2-yl) phosphonamido] furanyljthiazole [4:1 (vol:wt), methanol: Formula I] and heating the solution to 50 0 C. The heating source was turned off and water was added [2:1 (vol:wt), wateπFormula I]. The solution was allowed to cool to ambient temperature and then stirred again at ambient temperature. The mixture was then cooled to 3 0 C. The mixture was filtered and the filter cake washed with 2:1 (vol:vol) methanol:water and dried.
A representative XRPD pattern (Inel XRG-3000) of Form B is shown in Figure 3. The peaks in the list below are selected from XRPD images that represent clear signals above the noise level. Peak positions can be +/- 0.2 °2theta.
* Weak signals
Form B material is non-hygroscopic, anhydrous, crystalline solid with a melting point at approximately 156-162 0 C, as determined by DSC and hot-stage microscopy. The single 5 crystal structure of Form B was also determined. A calculated XRPD from the single crystal data is shown in Figure 4.
Single crystals of Form B were generated through the slow evaporation of an acetone/water 2:1 solution.
A colorless needle Of C 24 H 37 N 4 O 7 PS having approximate dimensions of 0.48 x 0.15 x
10 0.10 mm, was mounted on a glass fiber in random orientation. Preliminary examination and data collection were performed with Mo K a radiation (λ = 0.71073 A) on a Nonius KappaCCD diffractometer. Refinements were performed on an LINUX PC using SHELX97 [Sheldrick, G.M. Shelx97, A Program for Crystal Structure Refinement, University of Gottingen, Germany, 1997].
] 5 Cell constants and an orientation matrix for data collection were obtained from least- squares refinement using the setting angles of 43922 reflections in the range of 2° < θ < 25°. The refined mosaicity from DENZO/SCALEPACK [Otwinowski, Z, Minor, W. Methods En∑ymol. 1997, 276, 307] was 0.30° indicating good crystal quality. The space group was determined by the program ABSEN [McArdle, P.C. J. Appl. Cryst. 1996, 29, 306]. From the
20 systematic presence oϊhOl l=2n and OkO k=2n, and from subsequent least-squares refinement, the space group was determined to be P2;/c (no. 14). The data were collected to a maximum 2 θ value of 51.4°, at a temperature of 150 ± 1 K.
A total of 43922 reflections were collected, of which 10791 were unique. Lorentz and polarization corrections were applied to the data. The linear absorption coefficient is 2.0 cm "1
25 for Mo K a radiation. An empirical absorption correction using SCALEPACK [Otwinowski,
Z, Minor, W. Methods En∑ymol. 1997, 276, 307] was applied. Transmission coefficients ranged from 0.939 to 0.980. Intensities of equivalent reflections were averaged. The agreement factor for the averaging was 9.9% based on intensity.
The structure was solved by direct methods using PATTY in DIRDIF99 [Beurskens, P.T.; Beurskens, G.; deGelder, R.; Garcia-Granda, S.; Gould, R.O.; Israel, R.; Smits, J.M. M.
The DIRDIF-99 Program System Crystallography Laboratory, Univ. of Nijmegen, The
Netherlands, (1999)]. The remaining atoms were located in succeeding difference Fourier syntheses. Hydrogen atoms were included in the refinement but restrained to ride on the atom to which they are bonded. The structure was refined in full-matrix least-squares by minimizing the function:
σ4 F -\ -\ F <
The weight w is defined as \l[cf{F 0 2 ) + (0.0664Ff +(0.0000P)], where P = (F 0 2 +2F c 2 )/3.
Scattering factors were taken from the "International Tables for Crystallography" [International Tables for Crystallography, Vol. C, Kluwer Academic Publishers; Dordrecht, The Netherlands, 1992, Tables 4.2.6.8 and 6.1.1.4]. Of the 10066 reflections used in the refinements, only the reflections with F 0 " > 2σ(F 0 ") were used in calculating R. A total of 5428 reflections were used in the calculation. The final cycle of refinement included 717 variable parameters and converged (largest parameter shift was < 0.01 times its estimated standard deviation) with unweighted and weighted agreement factors of:
λ = ∑ |^ o
-^ c
|/∑^ o
=0.048
The standard deviation of an observation of unit weight was 0.93. The highest peak in the final difference Fourier had a height of 0.44 e/A . The minimum negative peak had a height of - 0.39 e/A 3 . A calculated XRPD pattern was generated for Cu radiation using Mercury v 1.2.1 and the atomic coordinates, space group, and unit cell parameters from the single crystal data.
X-ray powder diffraction (XRPD) analyses were performed using an Inel XRG-3000 diffractometer equipped with a CPS (Curved Position Sensitive) detector with a 2θ range of 120°. Real time data were collected using Cu-Ka radiation starting at approximately 4 °2θ at a resolution of 0.03 °2θ. The tube voltage and amperage were set to 40 kV and 30 mA, respectively. The monochromator slit was set at 5 mm by 160 μm. The pattern is displayed from 2.5-40 °2θ. Samples were prepared for analysis by packing them into thin-walled glass capillaries. Each capillary was mounted onto a goniometer head that is motorized to permit spinning of the capillary during data acquisition. The samples were analyzed for 2 min. Instrument calibration was performed using a silicon reference standard. The monoclinic cell parameters and calculated volume are: a = 1 1.4905(4), b =
16.3218(10), c = 30.8664(17) A, a = 90.00,^ = 93.393(3), γ = 90.00°, F= 5778.7(5) A 3 . For Z = S and formula weight of 556.62 the calculated density is 1.28 g cm "3 . The space group was determined to be P2j/c (no. 14). The crystallographic data and data collection parameters are provided in Table 1. Differences in intensities between the experimental and calculated patterns are likely due to preferred orientation. Preferred orientation is the tendency for crystals, usually plates or needles, to align themselves with some degree of order. Preferred orientation can affect peak intensities, but not peak positions, in XRPD patterns. The slight shifts in peak location are likely due to the fact that the experimental powder pattern was collected at ambient temperature, and the single crystal data was collected at 150 K. Low temperatures are used in single crystal analysis to improve the quality of the structure.
Table 1. Crystallographic Data and Data Collection Parameters for Form B formula C 24 H 37 N 4 O 7 PS formula weight 556.62 space group Pl 1 Ic (No. 14) a, A 11.4905(4) b, λ 16.3218(10) c, λ 30.8664(17) β, deg 93.393(3) v, A 3 5778.7(5)
Z 8 dcaic, g cm "3 1.280 crystal dimensions, mm 0.48x0.15x0.10 temperature, K 150. radiation (wavelength, A ) Mo K x (0.71073) monochromator graphite linear abs coef, mm "1 0.205 absorption correction applied emρirical a transmission factors: min, max 0.94, 0.98 diffractometer Nonius KappaCCD h, k, I range O to 14 O to 19 -37 to 37
2θ range, deg 4.30°-51.41° mosaicity, deg 0.30 programs used SHELXTL
•Pooo 2368.0 weighting ϊ /[s 2 CF 0 2 HO.0664P) 2 +0.000(IP] where P=( F O 2 +2F C 2 )B data collected 43922 unique data 10791
0.099 data used in refinement 10066 cutoff used in i?-factor calculations F o 2 >2.0sCF o 2 ) data with I>2. Os (T) 5428 number of variables 717 largest shift/esd in final cycle 0.00
R(F 0 ) 0.048
RJF 0 2 ) 0.113 goodness of fit 0.932
1 Otwinowski Z. & Minor, W. Methods Enzymol. 1997, 276, 307
A comparison of the calculated XRPD and experimental XRPD is shown is Figure 5. Form B is thermodynamically the most stable form as determined by interconversion slurries with Forms A and C-E.
TG analysis (Figure 6) demonstrated a weight loss of <0.2% at 147 0 C indicating that Form B is non-solvated. DSC data (Figure 6) revealed a single endothermic transition with a peak maximum at about 161 0 C. This endotherm is attributed to a melt base on hot-stage microscopy.
Automated moisture sorption/desorption analysis of Form B sample showed an insignificant weight gain of 0.15% at 95% RH. Upon desporption to 5% RH, the sample returned to its initial mass.
Example 3. Form C:
Form C was generated by slowly cooling a saturated acetonitrile solution of Formula I or from a fast evaporation of an acetonitrile solution of Formula I. There was about 0.6% of weight loss by TG analysis suggesting that Form C is anhydrous and non-solvated. The material exhibited a major endotherm at about 157 0 C and a minor endothermic event at about 170 0 C (Figure 7). The first endotherm is attributed to the melt based on hot-stage microscopy. The NMR spectrum of Form C material conforms to the structure of Formula I and no solvent signals were observed. A representative XRPD pattern (Shimadzu XRD- 6000) of Form C is shown in Figure 8. The peaks in the list below are selected from XRPD images that represent clear signals above the noise level. Peak positions can be +/- 0.2 °2theta.
Example 4. Form D:
In one method, Form D was generated by heating Form A to a boiling (142 0 C) in din-butyl ether (25 mL/g of Form A material). The mixture was cooled to 90 + 5 0 C and seed crystals of Form A were added. The mixture was stirred at 90 + 5 0 C for 2 hours then cooled to 22 0 C over 3 hours. The resulting solid was collected by filtration, washed with di-n-butyl ether and heptane, and dried in a vacuum oven.
In another method, Form D material was generated during VT-XRPD experiments utilizing Form C as starting material.
The DSC data showed a major endotherm at about 169 0 C (endothermic maximum) (Figure 9). A representative XRPD pattern (In el XRG-3000) of Form D is shown in Figure 10. A comparison of XRPD patterns for Form A-D is shown in Figure 11. The peaks in the list below are selected from XRPD images that represent clear signals above the noise level. Peak positions can be +/- 0.2 °2theta.
*Weak signals
Example 5. Form E:
Crystalline Form E was made by adding tetrahyrofuran (THF) to 2-Amino-5-(2,2- dimethyl-propionyl)-4-{2-[5-(N,N'-ethoxycarbonyl-2-methylpro p-2-yl) phosphonamido] furanylj-thiazole [2:1 (vol:wt) THF: Formula I]. The solution was heated to 40 0 C. N- heptane [10:1 (vol:wt) heptane: Formula I] was added rapidly while maintaining the temperature above 40 0 C. The mixture was cooled to ambient temperature and the filter cake was washed with n-heptane and dried under vacuum at 45-50 0 C. A representative XRPD pattern of Form E is shown in Figure 12. The peaks in the list below are selected from XRPD images that represent clear signals above the noise level. Peak positions can be +/- 0.2 °2theta.
* Weak signals
Example 6. Additional Methods: Table 2. below lists additional methods that can be used to prepare crystalline forms of
Formula I.
Table 1. Methods to produce crystalline forms of Formula I. Column three lists the crystalline form produced using the solvent and crystallization conditions of columns one and two, respectively. Abbreviations: SE = slow evaporation; SC = slow cool; FE = fast evaporation; RT = room temperature; VO = vacuum oven.
Example 7. Amorphous 2-amino-5-(2,2-dimethylpropionyl)-4-{[5-(N,N'-(2-ethoxy- carbonylprop-2-yl)phosphonamido] furan-2-yl}thiazole:
Amorphous material of Formula I can be produced by lyophilizing the compound of Formula I in a 1:1 or 2:1 mixture (vol:vol) of l,4-dioxane:H 2 O.
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