Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using Thiazolidinediones or Thiazolidinediones and Metformin

Study Overview
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Brief Summary
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This study is designed to compare the effects of twice-daily exenatide plus oral antidiabetic (OAD) agents and twice-daily placebo plus OAD with respect to glycemic control, as measured by hemoglobin A1c (HbA1c), in patients with type 2 diabetes who experience inadequate glycemic control with OAD alone.

Official Title
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Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using Thiazolidinediones or Thiazolidinediones and Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treated with thiazolidinedione (TZD) alone or in combination with metformin. TZD dose stable for at least 120 days prior to screening, and those patients on metformin must have been on a stable dose for at least 30 days prior to screening. HbA1c between 7.1% and 10.0%, inclusive. Body mass index (BMI) between 25 kg/m^2 and 45 kg/m^2. Exclusion Criteria: Patient previously in a study using exenatide or GLP-1 analogs. Treated with oral anti-diabetic medications other than TZD and metformin within 3 months of screening. Treated with oral insulin within 3 months of screening.

Ages Eligible for Study
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Minimum Age: 21 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: Exenatide<br>After a 2-week placebo lead-in period, exenatide will be given in an esclating dose along with the subject's current therapy regimen | Drug: exenatide<br>* After a 2-week placebo lead-in period (twice daily, given subcutaneously) in addition to their current therapy regimen, subjects will administer 20 mcg of exenatide (2 units [5 μg] ), twice daily by subcutaneous injection, for the first 4 weeks of therapy, and then 40 μL of study drug (4 units [10 μg] of exenatide) twice daily by subcutaneous injection, for the remaining 12 weeks of therapy.<br>* Other names: synthetic exendin-4;|
| Placebo Comparator: Placebo<br>After a 2-week placebo lead-in period, subjects will be given placebo (in equivalent amounts to exenatide) in addition to their current therapy regimen. | Drug: Placebo<br>* After a 2-week placebo lead-in period (twice daily, given subcutaneously) in addition to their current therapy regimen, subjects will administer placebo (in equivalent amounts to exenatide) for 16 weeks of therapy.<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 16, and if measured, any visits in between | Change in HbA1c from Baseline (Visit 3) to study termination at Week 16, and at all study visits in between | Baseline, Week 4, Week 8, Week 12, Week 16 | 
| Change from Baseline to Week 16 in fasting serum glucose (FSG) and glucose | Change from Baseline to Week 16 in FSG and glucose measured at different times throughout the day derived from 7-point self-monitored glucose (SMG) profile (glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, and at bedtime) | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects reaching the target HbA1c (<7%) | The percentage of subjects reaching the target HbA1c (<7%) will be summarized and compared by treatment | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 | 
| Change in body weight from Baseline to Week 16 | Change in body weight (kg) from Baseline to Week 16 | Baseline, Week 16 | 
| Change from Baseline to Week 16 in fasting serum glucose (FSG) and glucose | Change from Baseline to Week 16 in FSG and glucose measured at different times throughout the day derived from 7-point self-monitored glucose (SMG) profile (glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, and at bedtime) | Baseline, Week 16 | 
| Changes in beta cell function and insulin sensitivity between Baseline and Week 16 | Changes in beta cell function and insulin sensitivity as assessed by homeostasis model assessment (HOMA) analyses and the proinsulin/insulin ratio Between Baseline and Week 16 | Baseline, Week 16 | 
| Changes in lipids between Baseline and Week 16 | Changes from Baseline to Week 16 in serum lipids (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], fasting triglycerides, calculated low-density lipoprotein cholesterol [LDL-C] | Baseline, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exenatide, exendin-4, diabetes, Amylin, Lilly