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

Study Overview
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Brief Summary
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This study will assess safety and efficacy of exenatide in combination with a thiazolidinedione (TZD) and a TZD plus metformin over 26 weeks in adult patients with type 2 diabetes who have not achieved adequate glycemic control.

Official Title
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Safety and Efficacy of Exenatide in Patients With Type 2 Diabetes Using a Thiazolidinedione or a Thiazolidinedione 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: Diagnosed with type 2 diabetes If treated with a thiazolidinedione (TZD) alone, the TZD dose must have been stable for at least 120 days The dose of TZD must be: Rosiglitazone (≥4 mg/day) or pioglitazone (≥30 mg/day) The metformin dose has been stable for at least 90 days Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 10.0%, inclusive. Have a body mass index (BMI): 25 kg/m2 < BMI < 45 kg/m2. Exclusion Criteria: Have participated in this study previously or any other study using exenatide (AC2993/LY2148568) or glucagon-like peptide-1 (GLP-1) analogs, or have been previously treated with exenatide or GLP-1 analogs Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry. Have been treated with exogenous insulin for more than 1 week within the 2 months prior to screening Used drugs for weight loss (e.g., orlistat, rimonabant, sibutramine, or similar over-the-counter medications) within 3 months prior to screening. Are currently treated with any of the following excluded medications: Sulfonylurea or meglitinide derivatives (e.g., repaglinide or nateglinide) within 3 months prior to screening Alpha-glucosidase inhibitor (e.g., miglitol or acarbose) within 3 months of screening Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin or vildagliptin) within 3 months prior to screening Pramlintide acetate injection within 3 months prior to screening Drugs that directly affect gastrointestinal motility, including, but not limited to: Metoclopramide, cisapride, and chronic macrolide antibiotics Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding study start

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide twice daily (BID)<br> | Drug: exenatide<br>* subcutaneous injection, 5 mcg or 10 mcg, twice a day (BID)<br>* Other names: Byetta;|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* subcutaneous injection, volume equivalent to 5 mcg or 10 mcg of active drug, twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Hemoglobin (HbA1c) | Change in HbA1c from baseline to endpoint after 26 weeks of treatment (i.e., HbA1c at endpoint minus HbA1c at baseline) | baseline and 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <= 7% | Percentage of intent-to-treat (ITT) patients who had HbA1c > 7% at baseline that decreased to <= 7% at endpoint (Week 26 or early discontinuation) | 26 weeks | 
| Percentage of Patients Achieving HbA1c <= 6.5% | Percentage of ITT patients who had achieved HbA1c <= 6.5% at endpoint (Week 26 or early discontinuation) | 26 weeks | 
| Change in Fasting Serum Glucose (FSG) | Change in FSG from baseline to endpoint (26 weeks) | baseline and 26 weeks | 
| Change in Body Weight | Change in body weight from baseline to endpoint (26 weeks) | baseline and 26 weeks | 
| Change in Waist Circumference | Change in waist circumference from baseline to endpoint (26 weeks) | baseline and 26 weeks | 
| Change in Beta-cell Function | Change in homeostatic model assessment-beta cell (HOMA-B) from baseline to endpoint (Week 26) (outcome measure is presented as the ratio of endpoint HOMA-B divided by baseline HOMA-B). HOMA-B is a measure of pancreatic beta-cell function. | baseline and 26 weeks | 
| Change in Insulin Sensitivity. | Change in homeostatic model assessment-insulin sensitivity (HOMA-S) from baseline to endpoint (26 weeks) (outcome measure is presented as the ratio of endpoint HOMA-S divided by baseline HOMA-S). | baseline and 26 weeks | 
| Number of Subjects Who Experienced an Episode of Minor Hypoglycemia | Overall number of subjects who experienced an episode of minor hypoglycemia. | 26 weeks | 
| Change in Impact of Weight on Quality of Life (IWQOL)-Lite Score | IWQOL-Lite analysis of change from baseline to endpoint (26 weeks). IWQOL-Lite is a 31-item questionnaire, assessing the domains of physical function, self-esteem, sexual life, public distress, and work. Response categories for each item range from 1 = never true to 5 = always true. | baseline and 26 weeks | 
| Change in Euroqol - 5 Domain Quality of Life (EQ-5D) Score | EQ-5D Score - change from baseline to endpoint (26 weeks). EQ-5D is a 5-item questionnaire used to characterize current health states. The tool and accompanying visual analog scale (VAS) assess 5 domains of quality of life, including mobility, self-care, usual activity, pain, and anxiety/depression. Weights are used to score the responses to the 5 domains, with 3 options possible in each domain: extreme problems, some/moderate problems, or no problems. Scores range from 0 to 1, with a score of 1 representing a perfect health state. | baseline and 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide, metformin, thiazolidinedione, Byetta, Amylin, Lilly