Drug Interaction Study Between Dorzagliatin and Empagliflozin

Phase 1

Completed

• Conditions: Patients
• Interventions: Drug: Empagliflozin; Drug: Dorzagliatin

• Registration Number: NCT03790787
• Lead Sponsor: Hua Medicine Limited

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2018-12
• Study First Submitted: 2018-12-27
• Study First Submitted QC: 2018-12-28
• Study First Posted: 2019-01-02
• Study Start: 2019-04-18
• Primary Completion: 2020-03-15
• Study Completion: 2020-03-15
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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, at screening;
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 hypoglycemia within 3 months prior to screening;
4. Known contraindications to empagliflozin;
5. Clinically significant gastrointestinal disorder;
6. History or symptoms of clinically significant cardiovascular disease;
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 including within one year prior to screening;
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 empagliflozin;
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, HBsAg, or hepatitis C antibody;
20. Positive pregnancy test result;
21. Treated with any investigational drugs within 6 weeks prior to screening;
22. Reported history of prescription drug abuse;
23. Reported history of alcohol abuse
24. Reported history of donation or acute loss of blood during the 90 days prior to screening;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Sequential arm ABC	Empagliflozin	A: Empagliflozin 25 mg QD in the morning on Days 1-5; B: Empagliflozin 25 mg in the morning and Dorzagliatin 75 mg BID (morning and evening) on Days 6-10, with only the morning dose on Day 10; C: Dorzagliatin 75 mg BID (morning and evening) on Days 11-15, with only the morning dose on Day 15.
Sequential arm ABC	Dorzagliatin	A: Empagliflozin 25 mg QD in the morning on Days 1-5; B: Empagliflozin 25 mg in the morning and Dorzagliatin 75 mg BID (morning and evening) on Days 6-10, with only the morning dose on Day 10; C: Dorzagliatin 75 mg BID (morning and evening) on Days 11-15, with only the morning dose on Day 15.

Primary Outcome Measures

Name	Time	Method
GMR for Cmax of empagliflozin	up to 10 days	Geometric mean ratio (GMR) between combination and empagliflozin monotherapy for Cmax of empagliflozin
GMR for AUC0-24h of empagliflozin	up to 10 days	GMR between combination and empagliflozin in monotherapy for AUC0-24h of empagliflozin
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 in 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
12-lead ECG	up to 15 days	Number of participants with abnormal ECG VR,, PR, QRS and QT

Secondary Outcome Measures

Name	Time	Method
iCmax of glucose	up to 15 days	The incremental peak plasma concentration of glucose 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
iCmax of insulin	up to 15 days	The incremental peak plasma concentration of insulin post OGTT
iAUC0-4h of insulin	up to 15 days	The incremental area under the concentration-time curve of insulin in 4 hours post OGTT
iCmax of C-peptide	up to 15 days	The incremental peak plasma concentration of C-peptide 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

Trial Locations

Locations (1)

Frontage Clinical Services Inc.; 🇺🇸 Hackensack, New Jersey, United States