Drug Interaction Study Between Dorzagliatin and Sitagliptin

A Phase 1, Open-Label, Sequential, Multiple-Dose, Drug-Drug Interaction Study of Dorzagliatin and Sitagliptin in Subjects With Type 2 Diabetes Mellitus

This is a Phase 1, open-label, sequential, multiple-dose, drug interaction study of glucokinase activator dorzagliatin and sitagliptin in subjects with T2DM. Pharmacokinetics and pharmacodynamics when dorzagliatin and sitagliptin given alone and in combination will be studied.

Inclusion Criteria:

1. Subjects diagnosed with T2DM within at least 3 months prior to screening
2. Male and/or female subjects between the ages of 30 and 65 years, inclusive;
3. Body Mass Index (BMI) of 19 to 38 kg/m2, inclusive;
4. Fasting C-peptide test result >0.3 nmol/L (>0.90 ng/mL);
5. HbA1c ≥7% and ≤10.5%;

Exclusion Criteria:

1. Fasting blood glucose at screening or Day -1 ≤110 or ≥270 mg/dL;
2. Type 1 diabetes mellitus;
3. Reported incidence of severe or serious hypoglycemia within 3 months prior to screening;
4. Known contraindications to sitagliptin;
5. Clinically significant gastrointestinal disorder;
6. History or symptoms of clinically significant cardiovascular disease within one year prior to screening;
7. History of more than three urinary tract infections and/or more than three genital fungal infections in the last 12 months;
8. Reported history of clinically significant central nervous system disease;
9. Reported history of liver disease;
10. Reported history of clinically significant renal disease;
11. Estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m2;
12. Acute or chronic metabolic acidosis, including diabetic ketoacidosis;
13. Known or suspected malignancy;
14. Any reported hypersensitivity or intolerance to sitagliptin;
15. Antidiabetic treatment with insulin, sulfonylureas, thiazolidinediones or GLP-1 agonist within 3 months prior to screening;
16. Systolic blood pressure <90 or >160 mmHg or diastolic blood pressure <60 or >100 mmHg at screening;
17. A hospital admission or major surgery within 90 days prior to screening;
18. Uncontrolled hypertriglyceridemia >500 mg/dL;
19. Positive blood screen for HIV, hHBsAg, or hepatitis C antibody;
20. Positive pregnancy test result;
21. Female is breast-feeding or planning to become pregnant;
22. Treated with any investigational drugs within 6 weeks prior to screening;
23. Reported history of prescription drug abuse;
24. Reported history of alcohol abuse;
25. Reported history of donation or or acute loss of blood during the 90 days prior to screening;