Drug-Drug Interaction Study of Glucokinase Activator HMS5552 and Metformin in T2DM

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Metformin; Drug: HMS5552

• Registration Number: NCT02597400
• Lead Sponsor: Hua Medicine Limited

Brief Summary

This is a Phase 1, open-label, sequential, multiple-dose, drug-drug interaction study of GK activator HMS5552 and metformin in patients with type 2 diabetes mellitus (T2DM).

Detailed Description

This is a Phase 1, open-label, sequential, multiple-dose, drug-drug interaction study of GK activator HMS5552 and metformin in patients with type 2 diabetes mellitus (T2DM). The study is to assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM. The study is also to evaluate the safety and tolerability of HMS5552 with simultaneous administration of metformin in subjects with T2DM.

Study Timeline

• Study Start: 2015-10
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Study First Submitted: 2015-10-18
• Study First Submitted QC: 2015-11-03
• Study First Posted: 2015-11-05
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-16
• Last Update Posted: 2016-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Male and/or female subjects between the ages of 18 and 70 years
• Body Mass Index (BMI) of approximately 22 to 38kg/m2
• HbA1c ≥7% and ≤12%
• Are capable of giving informed consent and complying with study procedures

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Exclusion Criteria

• fasting blood glucose ≤110 or ≥270mg/dL
• Type 1 diabetes mellitus, or latent autoimmune diabetes in adults
• History or symptoms of clinically significant cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, or congestive heart disease within one year of screening
• History of liver disease and clinically significant renal disease
• Known hypersensitivity to metformin hydrochloride;
• Positive pregnancy test result;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HMS5552 and Metformin	HMS5552	All subjects will receive the following: * Metformin500 mg BID on Days 1-2, only the morning dose on Day 3. Metformin will be taken 30 minutes prior to meals; * Metformin 500 mg BID and HMS5552 50 mg BID on Days 4-7, only the morning dose on Day 8. Metformin and HMS5552 will be taken 30 minutes prior to meals; * HMS5552 50 mg BID on Days 9 -12, only the morning dose on Day 13. HMS5552 will be taken 30 minutes prior to meals.
HMS5552 and Metformin	Metformin	All subjects will receive the following: * Metformin500 mg BID on Days 1-2, only the morning dose on Day 3. Metformin will be taken 30 minutes prior to meals; * Metformin 500 mg BID and HMS5552 50 mg BID on Days 4-7, only the morning dose on Day 8. Metformin and HMS5552 will be taken 30 minutes prior to meals; * HMS5552 50 mg BID on Days 9 -12, only the morning dose on Day 13. HMS5552 will be taken 30 minutes prior to meals.

Primary Outcome Measures

Name	Time	Method
The primary pharmacokinetics parameters of Cmax To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	13 days	HMS5552 and metformin PK parameters: PK parameters (Cmax) will be computed for each subject per day with non-compartmental methods using the actual sampling times. Descriptive statistics will be calculated for the PK parameters per day (Days 3, 8 and 13).; The effect of metformin on the exposure of HMS5552 will be determined by a PK comparison between the exposure of HMS5552 on Day 13 vs. on Day 8. The effect of HMS5552 on the exposure of metformin will be determined by a PK comparison between the exposure of metformin on Day 8 vs. on Day 3.

Secondary Outcome Measures

Name	Time	Method
The pharmacokinetics parameters of Tmax To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	13 days	HMS5552 and metformin PK parameters: PK parameters ( Tmax) will be computed for each subject per day with non-compartmental methods using the actual sampling times. Descriptive statistics will be calculated for the PK parameters per day (Days 3, 8 and 13).; The effect of metformin on the exposure of HMS5552 will be determined by a PK comparison between the exposure of HMS5552 on Day 13 vs. on Day 8. The effect of HMS5552 on the exposure of metformin will be determined by a PK comparison between the exposure of metformin on Day 8 vs. on Day 3.
The pharmacokinetics parameters of AUC0-24hr To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	13 days	HMS5552 and metformin PK parameters: PK parameters (AUC0-24hr) will be computed for each subject per day with non-compartmental methods using the actual sampling times. Descriptive statistics will be calculated for the PK parameters per day (Days 3, 8 and 13).; The effect of metformin on the exposure of HMS5552 will be determined by a PK comparison between the exposure of HMS5552 on Day 13 vs. on Day 8. The effect of HMS5552 on the exposure of metformin will be determined by a PK comparison between the exposure of metformin on Day 8 vs. on Day 3.
Safety assessments includes monitoring of adverse events (AEs), vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, resting 12-lead electrocardiograms (ECGs), and physical examination findings.	13 days	Safety assessments will include monitoring of adverse events (AEs), blood glucose via glucometer readings, vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, resting 12-lead electrocardiograms (ECGs), and physical examination findings on Day 13 , Day 8 and Day-1
Pharmacodynamic responses (serum levels) of glucose, insulin and C-peptide will be evaluated.	13 days

Trial Locations

Locations (1)

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