Efficacy and Safety of SHR3824 in Combination With Metformin in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to obtain information on efficacy and safety of SHR3824 with metformin over 24 weeks and 52 weeks in metformin monotherapy poorly glycemic controlled chinese Type 2 Diabetes. Efficacy and safety will be evaluated by comparing the effect of SHR3824 with metformin to placebo with metformin when given in oral doses.

Detailed Description
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A phase III clinical study on efficacy and safety of SHR3824 combined with metformin for type 2 diabetes with poor glucose control in metformin monotherapy (multicenter, randomized, double-blind, placebo-parallel control). The 450 subjects received at least eight weeks of metformin monotherapy at a steady dose of 1500 mg or more before screening. Evaluation of efficacy: compared with the group of placebo combined with metformin, HbA1c, fasting plasma glucose, postprandial plasma glucose, fasting body weight and blood pressure changes in the SHR3824 with metformin group

Official Title
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Clinical Trial to Evaluate the Efficacy and Safety of SHR3824 Combined With Metformin in Metformin Monotherapy Poorly Glycemic Controlled Chinese Type 2 Diabetic Patients

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo
* Drug: SHR3824
* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of type 2 diabetes mellitus; Patients with type 2 diabetes mellitus treated with metformin monotherapy for ≥ 8 weeks and poor glycemic control, metformin dose stabilized ≥1500mg / day; FPG<=15mmol/L; Hemoglobin A1c levels >=7.0% and <=10.5%; Body mass index (BMI) 19 to 35 kg/m2; Exclusion Criteria: Type I diabetes mellitus, diabetes mellitus resulting from pancreatic disorder, or secondary diabetes mellitus (acromegaly, Cushing's syndrome, etc.); Past or current history of severe diabetic complications (proliferative diabetic retinopathy, stage III or later stage overt nephropathy, diabetic ketoacidosis, or serious diabetic neuropathy); Systolic blood pressure of ≥160 mmHg or diastolic blood pressure of ≥100 mmHg on the start or end day of the run-in period; History of myocardial infarction, unstable angina, or cerebrovascular disorder within 6 months before the start of the run-in period; Past or current history of malignant tumor; Past or current history of drug hypersensitivity such as shock and anaphylactoid symptoms; Pregnant women, lactating mothers, or women of childbearing potential; Any condition that subjects are assessed to be ineligible by the investigator (sub investigator).

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: SHR3824+Metformin, Placebo+Metformin<br>once daily for SHR3824 and placebo, three times daily for metformin, 24 weeks | Drug: Placebo<br>* Once daily, 24 weeks<br>|
| Experimental: SHR3824 5 mg+Metformin<br>once daily for SHR3824, three times daily for metformin, 52 weeks | Drug: SHR3824<br>* Once daily, 52 weeks<br>Drug: metformin<br>* Three times daily, 52 weeks<br>|
| Experimental: SHR3824 10 mg+Metformin<br>once daily for SHR3824, three times daily for metformin, 52 weeks | Drug: SHR3824<br>* Once daily, 52 weeks<br>Drug: metformin<br>* Three times daily, 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in HbA1c Levels | Compared with the placebo with metformin group, mean change in HbA1c Levels in SHR3824 with metformin group | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in Fasting Plasma Glucose | Compared with the placebo with metformin group, mean change in Fasting Plasma Glucose Levels in SHR3824 with metformin group | Baseline to Week 24 | 
| The number of volunteers with adverse events as a measurement of safety | Compared with the placebo with metformin group, the incidence of adverse events in SHR3824 with metformin group | Baseline to Week 52 |