Phase III Study to Evaluate Safety and Efficacy of Added Exenatide Versus Placebo to Titrated Basal Insulin Glargine in Inadequately Controlled Patients With Type II Diabetes Mellitus

Study Overview
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Brief Summary
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Study D5553C00002 is a multicenter, randomized, double-blind, placebo-controlled, parallel group, Phase 3 study to compare the safety and efficacy of exenatide once weekly (EQW) added to titrated basal insulin glargine with or without metformin to placebo added to titrated basal insulin glargine with or without metformin in patients with type 2 diabetes mellitus (T2DM). Eligible patients will be randomized at Visit 5 (Day 1) to receive either EQW added to titrated basal insulin glargine, with or without metformin ≥1500 mg/day, or placebo added to titrated basal insulin glargine, with or without metformin ≥1500 mg/day, during the 28-week treatment period.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Once Weekly Exenatide Therapy Added to Titrated Basal Insulin Glargine Compared to Placebo Added to Titrated Basal Insulin Glargine in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine With or Without Metformin

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Exenatide
* Drug: Exenatide matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Has a diagnosis of Type 2 Diabetes Mellitus (T2DM) Has HbA1c of 7.5% to 12.0%, inclusive, at Visit 1 (Screening). Has fasting plasma glucose (FPG) concentration <280 mg/dL (15.6 mmol/L) at Visit 1 (Screening) Treated with basal insulin glargine at a dose of ≥20 units/day once daily for at least 6 weeks prior to Screening, in combination with diet and exercise alone or in combination with: a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1 a stable dose of metformin (≥1500 mg/day) for at least 8 weeks prior to Visit 1 (Screening) and a stable dose of sulfonylurea for at least 8 weeks prior to the Screening visit Exclusion criteria: Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening) History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1 Positive serological test for hepatitis B or hepatitis C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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: Exenatide<br>Exenatide 2 mg 1 time per week + titrated basal insulin glargine with or without metformin | Drug: Exenatide<br>* 2 mg weekly suspension injection<br>|
| Placebo Comparator: Placebo<br>Placebo 2 mg 1 time per week + titrated basal insulin glargine with or without metformin | Drug: Exenatide matching placebo<br>* Once weekly Placebo injection<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 28 | To compare the change from baseline in HbA1c achieved with exenatide once weekly (EQW) added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. SU= sulfonylurea. | Baseline to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline to Week 28 | To compare the change from baseline in body weight achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. | Baseline to Week 28 | 
| Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test (MTT) | To compare the change from baseline in 2-hour postprandial glucose after a standard MTT achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. | Baseline to Week 28 | 
| Percentage of Participants Achieving HbA1c <7.0% at Week 28 | To compare the percentage of participants achieving HbA1c <7.0% between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. | Baseline to Week 28 | 
| Change From Baseline to Week 28 in Daily Insulin Dose | To compare the change from baseline in daily insulin dose achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. | Baseline to Week 28 | 
| Percentage of Participants Achieving HbA1c <7.0% at Week 28, No Weight Gain at Week 28, and No Major Hypoglycemia Over 28 Weeks | To compare the percentage of participants achieving HbA1c <7.0% at Week 28, no weight gain at Week 28, and no major hypoglycemia over 28 weeks between EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin. | Baseline to Week 28 | 
| Change in Seated Systolic Blood Pressure From Baseline to Week 28 | To compare the change from baseline in seated systolic blood pressure achieved with EQW added to titrated basal insulin glargine to placebo added to titrated basal insulin glargine, with or without metformin, after 28 weeks of double-blind treatment. | Baseline to Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Placebo, Diabetes Mellitus, Exenatide, Diabetes drug, Treatment efficacy, Metabolism, Cardiovascilar metabolic