A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2)

Study Overview
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Brief Summary
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This study will compare the benefits of exenatide once weekly treatment to those achieved by the approved antidiabetic therapies sitagliptin and pioglitazone in subjects whose type 2 diabetes is managed with metformin therapy alone. The safety and tolerability of the three treatment regimens will also be compared.

Official Title
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A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Long-Acting Release(Once Weekly) to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: sitagliptin
* Drug: pioglitazone
* Drug: placebo tablet
* Drug: placebo once weekly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has been diagnosed with type 2 diabetes mellitus Has a hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at study start Has a body mass index (BMI)of 25 kg/m2 to 45 kg/m2, inclusive, at study start Has been on a stable treatment regimen of metformin for a minimum of 2 months prior to study start Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start: Hormone replacement therapy (female subjects) Oral contraceptives (female subjects) Antihypertensive agents Lipid-lowering agents Thyroid replacement therapy Antidepressant agents Drugs known to affect body weight, including prescription medications (e.g. orlistat [XENICAL®], sibutramine [MERIDIA®], topiramate [TOPAMAX®]) and over-the-counter antiobesity agents Exclusion Criteria: Has been previously exposed to exenatide once weekly Has donated blood within 60 days of study start or is planning to donate blood during the study Currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications: Exenatide (BYETTA®) or any Dipeptidyl peptidase-4 DPP-4)inhibitor, sulfonylurea (SU), thiazolidinedione (TZD), or glucagon-like peptide (GLP)-1 analog within 3 months prior to study start Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption Drugs interacting with the CYP2C8 enzyme system, including gemfibrozil (LOPID®) and rifampin Has received any investigational drug within 1 month (or five half-lives of investigational drug, whichever is greater) of study start Has previously experienced a clinically significant adverse event (e.g., significant edema) related to TZD or DPP-4 inhibitor use

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: 1<br> | Drug: exenatide once weekly<br>* subcutaneous injection, 2.0mg, once a week<br>Drug: placebo tablet<br>* oral tablet, once a day<br>|
| Active Comparator: 2<br> | Drug: sitagliptin<br>* oral tablet, 100mg, once a day<br>* Other names: Januvia;Drug: placebo once weekly<br>* subcutaneous injection, once a week<br>|
| Active Comparator: 3<br> | Drug: pioglitazone<br>* oral tablet, 45mg, once a day<br>Drug: placebo once weekly<br>* subcutaneous injection, once a week<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 26 | Absolute change in HbA1c from baseline (Day 1) to Week 26 [Week 26 - Baseline]. | Day 1, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 | Percentages of subjects achieving HbA1c target values of <7% at Week 26. | Week 26 | 
| Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 | Percentages of subjects achieving HbA1c target values of <=6.5% at Week 26. | Week 26 | 
| Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 | Percentages of subjects achieving HbA1c target values of <=6.0% at Week 26. | Week 26 | 
| Change in Body Weight From Baseline to Week 26 | Change in body weight from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Change in Fasting Plasma Glucose From Baseline to Week 26 | Change in fasting plasma glucose from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Change in Systolic Blood Pressure From Baseline to Week 26 | Change in systolic blood pressure from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Change in Diastolic Blood Pressure From Baseline to Week 26 | Change in diastolic blood pressure from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Change in Fasting Total Cholesterol From Baseline to Week 26 | Change in fasting total cholesterol from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 | Change in fasting HDL from baseline (Day 1) to Week 26. | Day 1, Week 26 | 
| Ratio of Fasting Triglycerides at Week 26 to Baseline | Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline. | Day 1, Week 26 | 
| Assessment on Event Rate of Treatment-emergent Hypoglycemic Events | Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration < 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration < 54 mg/dL prior to treatment and not classified as major hypoglycemia. | Day 1 to Week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide once weekly, Byetta, sitagliptin, Januvia, thiazolidinedione, Amylin, Lilly, Pioglitazone