Long-term Efficacy and Safety of HMS5552 add-on to Metformin in T2DM Subjects

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety and population PK of HMS5552 add-on to Metformin in adult type 2 diabetic subjects. There will be 2 groups in the first 24 weeks, one group will receive HMS5552 plus Metformin, while the other group will receive placebo plus Metformin; after 24 weeks, all subjects will receive HMS5552 plus Metformin for 28 weeks.

Detailed Description
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This study is a phase III study in subjects with T2DM. As designed, the study will start with a 4-week, single-blind, placebo run-in period based on diet and exercise interventions for screening eligible subjects, meanwhile, subjects are treated with Metformin (Glucophage) at 1500mg/day as basic therapy throughout the treatment period. 3 weeks after run-in, eligibility is confirmed with required laboratory tests at -5±2 days prior to randomization. The eligible subjects are randomly assigned to HMS5552 75mg BID group or placebo BID group with ratio 1:1 to receive a 24-week double-blind treatment. Then all subjects receive 28-week open-label treatment of HMS5552 75mg BID add-on to Metformin. After 52-week treatment, all investigational drugs should be discontinued, followed by 1 week for safety evaluation. The dosage of Metformin (Glucophage) should be maintained at 1500 mg/day from run-in period to treatment completion.

Official Title
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A 24-week Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Study to Evaluate the Efficacy and Safety of HMS5552 add-on to Metformin With Additional 28-week Open-label Treatment to Evaluate the Safety in T2DM Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: HMS5552
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 75 years old; T2DM and treated with Metformin ≥ 1500mg/day constantly for at least 12 consecutive weeks; 7.5% ≤ HbA1c ≤ 10.0% at screening; 18.5 kg/m2 < BMI < 35.0 kg/m2 at screening; Exclusion Criteria: Any anti-diabetic therapy other than Metformin within 12 weeks before screening; Received insulin therapy more than 30 days within 1 year before screening; Fasting C-peptide <0.81 ng/ml (0.27 nmol/L) at screening; Medical history of severe hypoglycemia or frequent hypoglycemia, diabetic ketoacidosis, diabetes lactic acidosis or hyperosmotic nonketotic diabetic coma, severe cardio-cerebrovascular, unstable or rapidly progressive kidney disease, active liver diseases, diagnosed mental disease etc. T1DM;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMS5552<br>75mg BID | Drug: HMS5552<br>* BID oral administration<br>* Other names: Glucokinase Activator (GKA);|
| Placebo Comparator: Placebo<br>BID | Drug: Placebo<br>* BID oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c | The change of HbA1c from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline | The change of 2-hour postprandial plasma glucose (2h-PPG) from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment | 24 weeks | 
| The change of fasting plasma glucose (FPG) from baseline | The change of fasting plasma glucose (FPG) from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment | 24 weeks | 
| The proportion of subjects with HbA1c < 7.0% | HbA1c response rate by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects after 24-week double-blind treatment | 24 weeks | 
| The change of HbA1c from baseline at each visit over time, except at Week 24 | The change of HbA1c from baseline by comparing HMS5552 75 mg BID in combination with Metformin with Placebo BID in combination with Metformin in T2DM subjects at each visit over time, except at Week 24 | 24 weeks | 
| Incidence of Treatment-Emergent Adverse Events over time | including incidence of adverse events, incidence of hypoglycemic events, physical examination, vital signs, 12-lead ECG, clinical laboratory examinations (routine blood test, blood biochemistry and routine urine test). | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GKA, T2DM, HMS5552, Add-on therapy, Metformin