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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin
* Drug: HMS5552


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMS5552 and Metformin<br>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<br>* 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<br>* Other names: Glucophage®;Drug: HMS5552<br>* 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.<br>* Other names: GKA;|

What is the study measuring?
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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 |