Comparison Study of the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly Suspension to Sitagliptin and Placebo in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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To compare the effect on glycemic control (HbA1c) of exenatide suspension administered once weekly to that achieved by sitagliptin or placebo administered once daily for 28 weeks in subjects with type 2 diabetes mellitus.

Official Title
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A Randomized, Long-Term, Open-Label, 3-Arm, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly Suspension to Sitagliptin and Placebo in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Type 2

Intervention / Treatment
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* Drug: Exenatide once weekly suspension
* Drug: Sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years old Diagnosed with type 2 diabetes mellitus HbA1c of 7.1% to 11.0%, inclusive, at screening Has stable body weight, i.e., not varying by >3% for at least 3 months prior to screening Fasting plasma glucose concentration <280 mg/dL (15.5 mmol/L) at screening Body mass index of <45 kg/m2 at screening Has been treated with a stable regimen of ≥1500 mg/day metformin for a minimum of 2 months prior to Visit 1 (Screening) Exclusion Criteria: History of pancreatitis or triglycerides >=500 mg/dL Medullary carcinoma or multiple endocrine neoplasia (MEN2) or a family history of either History of renal transplantation, or is currently receiving renal dialysis, or has an estimated creatinine clearance <50 mL/min Active cardiovascular disease Presence or history of severe congestive heart failure Central nervous system disease, including epilepsy Liver disease History of severe gastrointestinal diseases Clinically significant malignant disease Repeated severe hypoglycemia within the last 6 months Any exposure to exenatide (BYETTA® or BYDUREON™) or any GLP-1 analog Any DPP-4 inhibitor within 3 months prior screening

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide once weekly suspension<br>Exenatide once weekly suspension 2mg subcutaneous injection | Drug: Exenatide once weekly suspension<br> <br> |
| Active Comparator: Sitagliptin 100mg<br>Overencapsulated Sitagliptin 100mg oral tablet once daily | Drug: Sitagliptin<br> <br> |
| Placebo Comparator: Placebo<br>Placebo oral capsule once daily | Drug: Placebo<br>* Placebo oral capsule once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Hemoglobin) From Baseline to Week 28 | Absolute change in HbA1c from baseline (Day 1, Visit 3) to Week 28/Study Termination (Visit 11). Hypothesis testing on the primary endpoint followed a serial gated procedure with all tests carried out at a 2-sided significance level of 0.05 to protect the family-wise error rate. These tests were conducted sequentially, and are presented in the statistical analysis section below in the order in which they were performed; each test was the gatekeeper of later tests. | Baseline to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving HbA1c <7% at Week 28 | Percentage of subjects achieving HbA1c target values of < 7.0% at Week 28/Study Termination. | Baseline to Week 28 | 
| Change in Fasting Plasma Glucose Concentrations From Baseline to Week 28 | The change in fasting plasma glucose concentrations from baseline (Day 1) to Week 28/Study Termination. | Baseline to Week 28 | 
| Change in Body Weight (kg) From Baseline to Week 28 | The change in body weight (kg) from baseline (Day 1) to Week 28/Study Termination. | Baseline to Week 28 | 
| Change in 2-hour Postprandial Glucose Concentrations From Baseline to Week 16 (Visit 8) | The change in 2-hour postprandial plasma glucose from baseline (Day 1) to Visit 8 (Week 16) was analyzed using a general linear model including treatment, and baseline HbA1c stratum (< 9% or ≥ 9%) as fixed factors, and the baseline 2-hour postprandial plasma glucose concentrations as a covariate. | Baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2, exenatide, Sitagliptin