A Study to Examine the Effects of Exenatide Once-Weekly Injection on Glucose Control and Safety in Asian Subjects

Study Overview
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Brief Summary
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Previous studies have suggested that a once-weekly formulation of exenatide may provide sustained glycemic control. These previous studies of exenatide once weekly have been conducted in non-Asian populations, so this study has been developed to support the local regulatory requirements of China, Korea, Japan, India, and Taiwan.

Official Title
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A Comparator-Controlled Study to Examine the Effects of Exenatide Once-Weekly Injection on Glucose Control (HbA1c) and Safety in Asian Subjects With Type 2 Diabetes Mellitus Managed With Oral Antidiabetic Medications

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: Have been diagnosed with type 2 diabetes. Have suboptimal glycemic control as evidenced by an HbA1c between 7.1% and 11.0% inclusive. Have a body mass index (BMI) of >21 kg/m2 and <35 kg/m2, inclusive. Have a history of stable body weight (not varying by >5% for at least 90 days prior to study start). Have been treated with a stable dose regimen of Met, SU, TZD, Met plus SU, Met plus TZD, or SU plus TZD for at least 90 days prior to study start. Exclusion Criteria: Have any contraindication for the OAD(s) that they use. Have a known allergy or hypersensitivity to exenatide BID, exenatide QW, or excipients contained in these agents. Have received chronic >14 consecutive days) systemic glucocorticoid therapy by oral, intravenous (IV), or intramuscular (IM) route or intra-articular steroid injection within 4 weeks prior to study start or are regularly treated with potent, inhaled steroids that are known to have a high rate of systemic absorption. Have been treated with drugs that promote weight loss (for example, GLP-1 analogue, orlistat, sibutramine, phenylpropanolamine, or similar over-the-counter medications) within 90 days of study start. Have been treated for >2 weeks with any of the following excluded medications within 90 days prior to study start: Insulin Dipeptidyl peptidase (DPP)-4 inhibitors (for example, sitagliptin or vildagliptin) Pramlintide acetate Drugs that directly affect gastrointestinal motility, including, but not limited to: Reglan® (metoclopramide), Propulsid® (cisapride), and chronic macrolide antibiotics. Have had prior exposure to exenatide Have previously completed or withdrawn from this study or any other study investigating exenatide BID or QW. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. Are currently enrolled in any other clinical study.

Ages Eligible for Study
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Minimum Age: 20 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>* 2.0mg subcutaneous injection, once a week<br>|
| Active Comparator: 2<br> | Drug: exenatide twice daily<br>* 5mcg subcutaneous injection twice a day (4 weeks), 10mcg subcutaneous injection twice a day (22 weeks)<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 26. | Change in HbA1c from baseline to Week 26. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c Targets <=7% at Week 26 | Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with HbA1c >7% at baseline). | Baseline, Week 26 | 
| Percentage of Patients Achieving HbA1c Targets <=6.5% at Week 26 | Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline). | Baseline, Week 26 | 
| Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 | Change in FSG from baseline to Week 26. | Baseline, Week 26 | 
| Change in Body Weight (BW) From Baseline to Week 26 | Change in BW from baseline to Week 26. | Baseline, Week 26 | 
| Change in Total Cholesterol (TC) From Baseline to Week 26 | Change in TC from baseline to Week 26. | Baseline, Week 26 | 
| Change in High-Density Lipoprotein (HDL) From Baseline to Week 26 | Change in HDL from baseline to Week 26. | Baseline, Week 26 | 
| Ratio of Triglycerides (TG) at Week 26 to Baseline | Ratio of TG (measured in mg/dL) at Week 26 to baseline. Log(Post-baseline TG) - log(Baseline TG); change from baseline to Week 26 is presented as ratio of Week 26 to baseline. | Baseline, Week 26 | 
| Change in Blood Pressure From Baseline to Week 26 | Change in systolic blood pressure and diastolic blood pressure from baseline to Week 26. | Baseline, Week 26 | 
| Assessment of Event Rate of Treatment-emergent Hypoglycemic Events | Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT. | Baseline 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, Amylin, Lilly