An Evaluation of Exenatide and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control.

Official Title
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An Evaluation of the Metabolic Effects of Exenatide, Rosiglitazone, and Exenatide Plus Rosiglitazone in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: exenatide
* Drug: rosiglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HbA1c of 6.8% to 10.0%, inclusive. Body mass index (BMI) of 25 kg/m^2 to 40 kg/m^2, inclusive. Exclusion Criteria: Have participated in this study previously, or have received exenatide, pramlintide acetate, GLP-1 analogs, or dipeptidyl peptidase-IV (DPP-IV) inhibitors 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 study start. This criterion includes drugs that have not received regulatory approval for any indication at the time of study start. Treated with any of the following medications: Thiazolidinedione within 5 months of screening; Sulfonylurea within 3 months of screening; Metformin/sulfonylurea combination therapy within 3 months of screening; Alpha-glucosidase inhibitor within 3 months of screening; Meglitinide within 3 months of screening; Insulin for more than 1 week within the 3 months prior to screening. Symlin (pramlintide acetate) injection or Byetta (exenatide) injection at any time Chronic (more than 2 weeks) or recent (within 4 weeks of study start) use of a drug that directly affects gastrointestinal motility 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 Regular use of a medication with addictive potential such as an opiate, narcotic, or tranquilizer Systemic antineoplastic agent Systemic transplantation medication Drugs for weight loss, including over-the-counter medications, within the 4 months prior to study start

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide Arm<br> | Drug: exenatide<br>* subcutaneous injection, 5mcg or 10mcg, twice a day<br>* Other names: Byetta;|
| Experimental: Exenatide plus Rosiglitazone Arm<br> | Drug: exenatide<br>* subcutaneous injection, 5mcg or 10mcg, twice a day<br>* Other names: Byetta;Drug: rosiglitazone<br>* oral tablet, 2mg or 4mg, twice a day<br>* Other names: Avandia;|
| Experimental: Rosiglitazone Arm<br> | Drug: rosiglitazone<br>* oral tablet, 2mg or 4mg, twice a day<br>* Other names: Avandia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ASIiAUC During a Hyperglycemic Clamp Test. | Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function. | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in AUC for Glucose During a Meal Challenge Test (MCT). | Change in AUC(15-180 min) for glucose during a MCT baseline to week 20. | Week 20 | 
| Change in Insulin Sensitivity Index as Measured by M-value. | Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20. | Week 20 | 
| Change in Insulin AUC in the First Stage From Baseline to Endpoint. | Change in insulin AUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test. | Week 20 | 
| Change in Insulin iAUC From Baseline to Endpoint. | Change in insulin iAUC in the first stage(uIU-min/ml) from baseline to week 20. First stage represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test. | Week 20 | 
| Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). | Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT. | Week 20 | 
| Change in AUC for C-peptide During a Meal Challenge Test (MCT). | Ratio (value at endpoint divided by value at baseline) of AUC(15-180 min) for C-peptide (nmol-min/L) during a MCT from baseline to week 20. | Week 20 | 
| Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). | Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20. | Week 20 | 
| Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). | Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20. | Week 20 | 
| Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). | Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20. | Week 20 | 
| Change in HbA1c | Change in HbA1c from baseline to week 20. | Week 20 | 
| Change in Fasting Serum Glucose Concentration. | Change in fasting serum glucose concentration from baseline to week 20. | Week 20 | 
| Change in Fasting C-peptide | Change in fasting C-peptide from baseline to week 20. | Week 20 | 
| Change in Fasting Insulin | Change in fasting insulin from baseline to week 20. | Week 20 | 
| Change in Fasting Proinsulin | Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline | Week 20 | 
| Change in Body Weight | Change in body weight from baseline to week 20. | Week 20 | 
| Change in Fasting Total Cholesterol. | Change in fasting total cholestrol from baseline to week 20. | Week 20 | 
| Change in Fasting HDL Cholesterol | Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20. | Week 20 | 
| Change in Fasting LDL Cholesterol | Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20. | Week 20 | 
| Change in Fasting Triglycerides | Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20. | Week 20 | 
| Change in Percent Body Fat During a Meal Challenge Test (MCT) | Change in percent body fat from baseline to week 20, as assessed during an MCT | 20 weeks | 
| Change in Body Fat Mass During a Meal Challenge Test (MCT) | Change in body fat mass form baseline to week 20, as assessed during an MCT | 20 weeks | 
| Change in Lean Body Mass During a Meal Challenge Test (MCT) | Change in lean body mass from baseline to week 20, as assessed during an MCT | 20 weeks | 
| Change in Waist Circumference | Change in waist circumference from baseline to week 20 | 20 weeks | 
| Change in Hip Circumference | Change in hip circumference form baseline to week 20 | 20 weeks | 
| Change in Waist-to-hip Ratio | Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20 | 20 weeks | 
| Incidence of Hypoglycemia Events | Number of subjects experiencing hypoglycemia at any point during the study | 20 weeks | 
| Hypoglycemia Rate Per 30 Days Per Patient | Average number of episodes of hypoglycemia per 30 days per patient | 20 weeks | 
| Pedal Edema Score | Pedal edema scores experienced by each patient throughout the study (1+ indicates a patient experienced a pedal edema score of 1 , 2, or 3; 2+ indicates a patient experienced a pedal edema score of 2 or 3, etc.) Scale: Slight pitting, no visible distortion, disappears rapidly A somewhat deeper pit than in 1+, but again no readily detectable distortion, and it disappears in 10 - 15 seconds The pit is noticeably deep and may last more than a minute; the dependent extremity looks fuller and swollen The pit is very deep, lasts as long as 2 - 5 minutes, and the dependent extremity is grossly distorted | 20 weeks | 

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