Long-term Efficacy and Safety of HMS5552 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 as monotherapy in adult type 2 diabetic subjects, there will be 2 groups in the first 24 weeks, one group will receive HMS5552 , while the other group will receive placebo ; after 24 weeks, all subjects will receive HMS5552 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. The eligible subjects are randomly assigned to HMS5552 75mg BID group or placebo BID group with ratio 2:1 to receive a 24-week double-blind treatment. Then all subjects receive 28-week open-label treatment of HMS5552 75mg BID . After 52-week treatment, all investigational drugs should be discontinued, followed by 1 week for safety evaluation.

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 With Additional 28-week Open-label Treatment to Evaluate the Safety of HMS5552 Alone 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 naive T2DM 3.7.5% ≤ HbA1c ≤ 11.0% at screening 4.18.5 kg/m2 < BMI < 35.0 kg/m2 at screening; Exclusion Criteria: T1DM Fasting C-peptide <1.0 ng/ml (0.33 nmol/L) at screening Medical history of severe 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

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 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 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 in T2DM subjects after 24-week double-blind treatment | 24 weeks | 
| The proportion of subjects with HbA1c < 7.0% | The HbA1c response rate in T2DM subjects after 24-week double-blind treatment | 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, monotherapy