A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5)

Study Overview
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Brief Summary
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This study will compare the effects of commercially manufactured exenatide once weekly and exenatide BID in subjects whose type 2 diabetes is managed with diet and exercise alone or with oral antidiabetic medications. The study will examine glycemic control (as measured by HbA1C), safety, and tolerability.

Official Title
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A Randomized, Open-Label, Parallel-Group, Comparator-Controlled, Multicenter Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: exenatide twice daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has been diagnosed with type 2 diabetes mellitus Has hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at screening Has a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening Has been treated with diet and exercise alone or in combination with a stable regimen of metformin (MET), a sulfonylurea (SU), a thiazolidinedione (TZD), a combination of metformin and an SU, a combination of metformin and a TZD, or a combination of an SU and a TZD for a minimum of 2 months prior to screening 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 screening: 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 ever been exposed to exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) analog Has received any investigational drug within one month (or five half-lives of the investigational drug, whichever is greater) of screening Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications: Any dipeptidyl peptidase 4 (DPP-4) inhibitor within 3 months prior to screening Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of screening Insulin within 2 weeks of screening or for more than 1 week within 3 months of screening 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

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: exenatide once weekly<br>* subcutaneous injection, 2.0mg, once a week<br>* Other names: BYDUREON;|
| Active Comparator: 2<br> | Drug: exenatide twice daily<br>* subcutaneous injection; 5mcg (4 weeks) and 10mcg (20 weeks); twice a day<br>* Other names: BYETTA;|

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 24 | Change in HbA1c from baseline (Day 1) to Week 24 [Week 24 - Baseline]. | Day 1, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving HbA1c Target of <7% | Percentages of subjects achieving HbA1c target value of <7% at Week 24. | Week 24 | 
| Percentage of Subjects Achieving HbA1c Target of <=6.5% | Percentages of subjects achieving HbA1c target values of <=6.5% at Week 24. | Week 24 | 
| Change in Fasting Plasma Glucose From Baseline to Week 24 | Change in fasting plasma glucose from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL | Percentages of subjects achieving fasting plasma glucose target of <=126 mg/dL at Week 24. | Week 24 | 
| Change in Body Weight From Baseline to Week 24 | Change in body weight from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Change in Sitting Systolic Blood Pressure From Baseline to Week 24 | Change in systolic blood pressure from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Change in Sitting Diastolic Blood Pressure From Baseline to Week 24 | Change in diastolic blood pressure from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Change in Total Cholesterol From Baseline to Week 24 | Change in total cholesterol from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Change in High-density Lipoprotein (HDL) From Baseline to Week 24 | Change in HDL from baseline (Day 1) to Week 24. | Day 1, Week 24 | 
| Ratio of Triglycerides at Week 24 to Baseline | Ratio of triglycerides (measured in mg/dL) at Week 24 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 24 | 
| Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | The major hypoglycemia category included 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 of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject. | Day 1 to Week 24 | 
| Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | The minor hypoglycemia category included events in which symptoms consistent with hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia. | Day 1 to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide once weekly, Byetta, Amylin, Lilly, Bydureon