Patients
Conditions
Brief summary
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.
Interventions
DRUGSitagliptin
Sitagliptin (Januvia® 100 mg tablets for oral administration)
DRUGDorzagliatin
Glucokinase activator currently under development
Sponsors
Hua Medicine Limited
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-lead ECG | up to 15 days | Number of participants with abnormal ECG VR,, PR, QRS and QT |
| GMR for AUC0-24h of sitagliptin | up to 10 days | GMR between combination and sitagliptin monotherapy for AUC0-24h of sitagliptin |
| GMR for Cmax of dorzagliatin | up to 15 days | GMR between combination and dorzagliatin monotherapy for Cmax of dorzagliatin |
| GMR for AUC0-24h of dorzagliatin | up to 15 days | GMR between combination and dorzagliatin monotherapy for AUC0-24h of dorzagliatin |
| Adverse events | up to 15 days | Number of participants with AEs |
| Abnormal vital signs | up to 15 days | Number of participants with abnormal vital signs (blood pressure, pulse rate, respiratory rate and oral temperature) |
| Abnormal clinical laboratory findings | up to 15 days | Number of participants with abnormal clinical laboratory findings |
| Geometric mean ratio (GMR) for Cmax of sitagliptin | up to 10 days | GMR between combination and sitagliptin monotherapy for Cmax of sitagliptin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| iCmax of C-peptide | up to 15 days | The incremental peak plasma concentration of C-peptide post OGTT |
| iAUC0-4h of glucose | up to 15 days | The incremental area under the concentration-time curve of glucose in 4 hours post OGTT |
| iAUC0-4h of C-peptide | up to 15 days | The incremental area under the concentration-time curve of C-peptide in 4 hours post OGTT |
| iCmax of GLP-1 | up to 15 days | The incremental peak plasma concentration of GLP-1 post OGTT |
| iAUC0-4h of GLP-1 | up to 15 days | The incremental area under the concentration-time curve of GLP-1 in 4 hours post OGTT |
| iCmax of glucose | up to 15 days | The incremental peak plasma concentration of glucose post OGTT |
Countries
United States
Outcome results
None listed