Drug Interaction Study Between Dorzagliatin and Empagliflozin

• ClinicalTrials.gov Identifier: NCT03790787
• Recruitment Status: Completed
• First Posted: January 2, 2019
• Last Update Posted: March 25, 2020
• Sponsor: Hua Medicine Limited
• Information provided by (Responsible Party): Hua Medicine Limited

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Patients	Drug: Empagliflozin; Drug: Dorzagliatin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label, Sequential, Multiple-Dose, Drug-Drug Interaction Study of Dorzagliatin and Empagliflozin in Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: April 18, 2019
• Actual Primary Completion Date: March 15, 2020
• Actual Study Completion Date: March 15, 2020

Arms and Interventions

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: Empagliflozin; Empagliflozin as Jardiance® 25 mg film-coated tablets for oral administration; Other Name: Jardiance; Drug: Dorzagliatin; Glucokinase activator currently under development; Other Name: HMS5552

Outcome Measures

Primary Outcome Measures :

1. Cmax,ss [ Time Frame: up to 5 days ]
   maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ
2. AUCτ,ss [ Time Frame: up to 5 days ]
   area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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;

Contacts and Locations

Locations

United States, New Jersey

Frontage Clinical Services Inc.

Hackensack, New Jersey, United States, 07601

Sponsors and Collaborators

Hua Medicine Limited

Investigators

• Principal Investigator: Gregory J Tracey, MD; Frontage Clinical Services, Inc.

More Information

• Responsible Party: Hua Medicine Limited
• ClinicalTrials.gov Identifier: NCT03790787
• Other Study ID Numbers: HMM0112
• First Posted: January 2, 2019
• Last Update Posted: March 25, 2020
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Empagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs