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

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

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

Study Overview

• Status: Unknown
• Conditions: Type2 Diabetes Mellitus
• Intervention / Treatment: Biological: rE-4 5 mcg; Biological: rE-4 10 mcg; Biological: Placebo 5 mcg; Biological: Placebo 10 mcg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 456
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: linong Ji, Ph.D; Phone Number: +86-01088325578; Email: jiln@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. T2DM
2. 7.0% ≤ HbA1c ≤ 11.0% at screening
3. FPG ≤13.8 mmol/L
4. 19 kg/m2 < BMI <35.0 kg/m2 at screening
5. All subjects provided written informed consent before participation

Exclusion Criteria:

1. T1DM
2. Patients treated previously with Exenatide or GLP-1 similar
3. At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 2.5 ULN
4. At screening visit estimated glomerular filtration rate (eGFR) ≤ 60 mL/min or Triglyceride(TG)≥ 5 mmol/L
5. Pancreatitis, cholecystitis, gallstones and other gastrointestinal diseases
6. 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
7. History of digestive diseases (e.g.pancreatitis, cholecystitis or gallstones)
8. Patients with severe renal impairment or end-stage renal disease
9. Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 110 mmHg) at screening visit.
10. Use of weight loss drugs within 3 months prior to screening visit
11. Have been treated with exogenous insulin, α-glucosidase, corticosteroid, DPP-4 inhibitor or pramlintide acetate within the 3 months prior to screening.
12. Severe gastrointestinal disease (e.g., gastroparesis)
13. Pregnancy or lactation, women of childbearing potential with no effective contraceptive method
14. Participant who participated in any drug clinical trial within the last 3 months prior to screening visit
15. History of severe hypersensitivity to rExenatide-4 or any product components

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rE-4 5 mcg; Placebo, then rE-4 5 mcg, then rE-4 5 mcg	Biological: rE-4 5 mcg; 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; Other Names: rExenatide-4
Experimental: rE-4 10 mcg; Placebo, then rE-4 5 mcg, then rE-4 10 mcg	Biological: rE-4 10 mcg; 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; Other Names: rExenatide-4
Placebo Comparator: Placebo 5 mcg; Placebo 5 mcg, then Placebo 5 mcg, then Placebo 5 mcg	Biological: Placebo 5 mcg; 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
Placebo Comparator: Placebo 10 mcg; Placebo 5 mcg, then Placebo 5 mcg, then Placebo 10 mcg	Biological: Placebo 10 mcg; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Investigators: Principal Investigator: linong Ji, Ph.D, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2017
• Primary Completion (Anticipated): December 30, 2018
• Study Completion (Anticipated): January 15, 2019

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 3, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Metformin; Sulfonylurea; Exenatide; rE-4
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: rE-4201706/PRO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No