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: 28 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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
• 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
Cmax,ss	maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ	up to 5 days
AUCτ,ss	area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ	up to 5 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, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; 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