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

A Phase 1, Open-Label, Sequential, Multiple-Dose, Drug-Drug Interaction Study of Glucokinase (GK) Activator HMS5552 and Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin; Drug: HMS5552

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 Type: Interventional
• Enrollment (Actual): 12
• 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: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HMS5552 and 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.

Drug: Metformin; 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; Other Names: Glucophage®; Drug: HMS5552; 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.; Other Names: GKA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary pharmacokinetics parameters of Cmax To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	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.	13 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pharmacokinetics parameters of Tmax To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	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.	13 days
The pharmacokinetics parameters of AUC0-24hr To assess the potential pharmacokinetic interaction between HMS5552 and metformin in subjects with T2DM	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.	13 days
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.	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	13 days
Pharmacodynamic responses (serum levels) of glucose, insulin and C-peptide will be evaluated.		13 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: October 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: October 18, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 16, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: HMM0104

Plan for Individual participant data (IPD)

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