The Effectivity and Safety Study of rExenatide-4 in Chinese Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This research is a randomized, double-blind,controlled trial. 456 Chinese subjects with Type 2 Diabetes Mellitus will be enrolled in the trial.

Detailed Description
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This is a multicenter, randomized, blinded, placebo-controlled study to assess the effects on glucose control of rE-4 as compared to placebo in patients with type 2 diabetes. Patients will be randomized into one of two rE-4 treatment arms or to placebo treatment and will continue with their required existing diabetes medications (metformin, a sulfonylurea or metformin and a sulfonylurea combination) throughout the study.

Official Title
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A Phase 3, Randomized, Double-Blind,Placebo-Controlled, Multicenter Study to Examine the Effect on Glucose Control (HbA1c) and Safety of rE-4 in Subjects With Type 2 Diabetes Mellitus Treated With Metformin, a Sulfonylurea, or Metformin and Sulfonylurea Combination

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Biological: rE-4 5 mcg
* Biological: rE-4 10 mcg
* Biological: Placebo 5 mcg
* Biological: Placebo 10 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T2DM 7.0% ≤ HbA1c ≤ 11.0% at screening FPG ≤13.8 mmol/L 19 kg/m2 < BMI <35.0 kg/m2 at screening All subjects provided written informed consent before participation Exclusion Criteria: T1DM Patients treated previously with Exenatide or GLP-1 similar At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 2.5 ULN At screening visit estimated glomerular filtration rate (eGFR) ≤ 60 mL/min or Triglyceride(TG)≥ 5 mmol/L Pancreatitis, cholecystitis, gallstones and other gastrointestinal diseases Within the last 12 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period History of digestive diseases (e.g.pancreatitis, cholecystitis or gallstones) Patients with severe renal impairment or end-stage renal disease Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg) at screening visit. Use of weight loss drugs within 3 months prior to screening visit Have been treated with exogenous insulin, α-glucosidase, corticosteroid, DPP-4 inhibitor or pramlintide acetate within the 3 months prior to screening. Severe gastrointestinal disease (e.g., gastroparesis) Pregnancy or lactation, women of childbearing potential with no effective contraceptive method Participant who participated in any drug clinical trial within the last 3 months prior to screening visit History of severe hypersensitivity to rExenatide-4 or any product components

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rE-4 5 mcg<br>Placebo, then rE-4 5 mcg, then rE-4 5 mcg | Biological: rE-4 5 mcg<br>* Placebo Lead In (5 mcg) for 4 weeks / rE-4 5 mcg for 4 weeks / rE-4 5 mcg for 26 weeks - All are subcutaneously injected twice daily<br>* Other names: rExenatide-4;|
| Experimental: rE-4 10 mcg<br>Placebo, then rE-4 5 mcg, then rE-4 10 mcg | Biological: rE-4 10 mcg<br>* Placebo Lead In (5 mcg) for 4 weeks / rE-4 5 mcg for 4 weeks / rE-4 10 mcg for 26 weeks - All are subcutaneously injected twice daily<br>* Other names: rExenatide-4;|
| Placebo Comparator: Placebo 5 mcg<br>Placebo 5 mcg, then Placebo 5 mcg, then Placebo 5 mcg | Biological: Placebo 5 mcg<br>* Placebo Lead In (5 mcg) for 4 weeks / Placebo 5 mcg for 4 weeks / Placebo 5 mcg for 26 weeks - All are subcutaneously injected twice daily<br>|
| Placebo Comparator: Placebo 10 mcg<br>Placebo 5 mcg, then Placebo 5 mcg, then Placebo 10 mcg | Biological: Placebo 10 mcg<br>* Placebo Lead In (5 mcg) for 4 weeks / Placebo 5 mcg for 4 weeks / Placebo 10 mcg for 26 weeks - All are subcutaneously injected twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from Baseline to Week 30 | Change in HbA1c from Baseline (Day 1) to study termination (Week 30) | Baseline (Day 1) to Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects achieving HbA1c target values of < 7% and ≤ 6.5% by Week 30 | The number of subjects achieving HbA1c target values of < 7% and ≤ 6.5% by study termination (Week 30) | Baseline (Day 1) and Week 30 | 
| Change in body weight from Baseline to each intermediate visit and Week 30 | Change in body weight (kg) from Baseline to each intermediate visit and Week 30 | Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 30 | 
| Change in FPG from Baseline to each intermediate visit and Week 30 | Change in Fasting Plasma Glucose from Baseline to each intermediate visit and Week 30 | Baseline (Day 1), Week 2, Week 4, Week, 6, Week 12, Week 18, Week 24, Week 30 | 
| Change in 7-SMBG from Baseline to Week 16，Week 24 and Week 30 | Change in glucose measurements before and 2h after the start of the morning,midday,and evening meals, and at bedtime from Baseline to Week 16，Week 24 and Week 30 | Baseline, Week 16，Week 24 and Week 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rE-4, Exenatide, Metformin, Sulfonylurea