Drug Interaction Study Between Dorzagliatin and Empagliflozin

A Phase 1, Open-Label, Sequential, Multiple-Dose, Drug-Drug Interaction Study of Dorzagliatin and Empagliflozin 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 empagliflozin in subjects with T2DM. Pharmacokinetics and pharmacodynamics when dorzagliatin and empagliflozin given alone and in combination will be studied.

Study Overview

• Status: Completed
• Conditions: Patients
• Intervention / Treatment: Drug: Dorzagliatin; Drug: Empagliflozin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Frontage Clinical Services Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential arm ABC; 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.	Drug: Dorzagliatin; Glucokinase activator currently under development; Other Names: HMS5552; Drug: Empagliflozin; Empagliflozin as Jardiance® 25 mg film-coated tablets for oral administration; Other Names: Jardiance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMR for Cmax of dorzagliatin	GMR between combination and dorzagliatin monotherapy for Cmax of dorzagliatin	up to 15 days
Adverse events	Number of participants with AEs	up to 15 days
Abnormal vital signs	Number of participants with abnormal vital signs (blood pressure, pulse rate, respiratory rate and oral temperature)	up to 15 days
Abnormal clinical laboratory findings	Number of participants with abnormal clinical laboratory findings	up to 15 days
12-lead ECG	Number of participants with abnormal ECG VR,, PR, QRS and QT	up to 15 days
GMR for Cmax of empagliflozin	Geometric mean ratio (GMR) between combination and empagliflozin monotherapy for Cmax of empagliflozin	up to 10 days
GMR for AUC0-24h of empagliflozin	GMR between combination and empagliflozin in monotherapy for AUC0-24h of empagliflozin	up to 10 days
GMR for AUC0-24h of dorzagliatin	GMR between combination and dorzagliatin in monotherapy for AUC0-24h of dorzagliatin	up to 15 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hua Medicine Limited
• Investigators: Principal Investigator: Gregory J Tracey, MD, Frontage Clinical Services, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2019
• Primary Completion (Actual): March 15, 2020
• Study Completion (Actual): March 15, 2020

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: December 28, 2018
• First Posted (Actual): January 2, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 20, 2025
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sodium-Glucose Transporter 2 Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Empagliflozin
• Other Study ID Numbers: HMM0112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No