The PK/PD, Efficacy, Safety and Tolerability Study of SHR3824 in Combination With Metformin in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of 3 different doses of SHR3824 compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin monotherapy (ie, treatment with a single drug) and have inadequate glycemic (blood sugar) control.

Official Title
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An Efficacy, Safety, and Tolerability Study of SHR3824 in the Treatment of Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: SHR3824
* Drug: Placebo
* 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; Hemoglobin A1c levels >=7.5% and <=10.5%; Body mass index (BMI) 25 to 45 kg/m2; Patient either has been treated with metformin for more than 8 weeks with dose more than 1500mg/day. 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 Placebo<br>SHR3824 Placebo , once daily, 12 weeks, Metformin, Three times daily, 500mg, background drug. | Drug: Placebo<br> <br> Drug: Metformin<br> <br> |
| Experimental: SHR3824 5 mg<br>SHR3824 5 mg , once daily, 12 weeks, Metformin, Three times daily, 500mg, background drug. | Drug: SHR3824<br> <br> Drug: Metformin<br> <br> |
| Experimental: SHR3824 10 mg<br>SHR3824 10 mg , once daily, 12 weeks, Metformin, Three times daily, 500mg, background drug. | Drug: SHR3824<br> <br> Drug: Metformin<br> <br> |
| Experimental: SHR3824 20 mg<br>SHR3824 20mg , once daily, 12 weeks, Metformin, Three times daily, 500mg, background drug. | Drug: SHR3824<br> <br> Drug: Metformin<br> <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 |  | Baseline to Week 12 | 
| The number of volunteers with adverse events as a measure of safety and tolerability |  | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in Fasting Plasma Glucose |  | Baseline to Week 12 | 
| Proportion of Participants Achieving Glycemic Response Defined as HbA1c <7% |  | Baseline to Week 12 |