Drug Interaction Study Between Dorzagliatin and Sitagliptin

Patients Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03790839
• Other study ID #: HMM0111
• Status: Completed
• Phase: Phase 1
• Start date: January 31, 2019
• Est. completion date: August 30, 2019

Study information

• Verified date: December 2018
• Source: Hua Medicine Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 30, 2019
• Est. primary completion date: August 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• Patients

Intervention

Drug:
• Sitagliptin
Sitagliptin (Januvia® 100 mg tablets for oral administration)
• Dorzagliatin
Glucokinase activator currently under development

Locations

Country	Name	City	State
United States	Frontage Clinical Services Inc.	Hackensack	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hua Medicine Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric mean ratio (GMR) for Cmax of sitagliptin	GMR between combination and sitagliptin monotherapy for Cmax of sitagliptin	up to 10 days
Primary	GMR for AUC0-24h of sitagliptin	GMR between combination and sitagliptin monotherapy for AUC0-24h of sitagliptin	up to 10 days
Primary	GMR for Cmax of dorzagliatin	GMR between combination and dorzagliatin monotherapy for Cmax of dorzagliatin	up to 15 days
Primary	GMR for AUC0-24h of dorzagliatin	GMR between combination and dorzagliatin monotherapy for AUC0-24h of dorzagliatin	up to 15 days
Primary	Adverse events	Number of participants with AEs	up to 15 days
Primary	Abnormal vital signs	Number of participants with abnormal vital signs (blood pressure, pulse rate, respiratory rate and oral temperature)	up to 15 days
Primary	Abnormal clinical laboratory findings	Number of participants with abnormal clinical laboratory findings	up to 15 days
Primary	12-lead ECG	Number of participants with abnormal ECG VR,, PR, QRS and QT	up to 15 days
Secondary	iCmax of glucose	The incremental peak plasma concentration of glucose post OGTT	up to 15 days
Secondary	iAUC0-4h of glucose	The incremental area under the concentration-time curve of glucose in 4 hours post OGTT	up to 15 days
Secondary	iCmax of C-peptide	The incremental peak plasma concentration of C-peptide post OGTT	up to 15 days
Secondary	iAUC0-4h of C-peptide	The incremental area under the concentration-time curve of C-peptide in 4 hours post OGTT	up to 15 days
Secondary	iCmax of GLP-1	The incremental peak plasma concentration of GLP-1 post OGTT	up to 15 days
Secondary	iAUC0-4h of GLP-1	The incremental area under the concentration-time curve of GLP-1 in 4 hours post OGTT	up to 15 days