Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The objectives of this clinical trial are to compare the effects of exenatide once weekly and insulin glargine on blood glucose control, body weight, lipids, safety, and tolerability.

Official Title
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Parallel Group Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus Treated With Oral Antidiabetic(s)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: exenatide once weekly
* Drug: insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: present with type 2 diabetes mellitus HbA1c between 7.1% and 11.0% inclusive body mass index (BMI) of >18kg/m2 and <35kg/m2, inclusive treated with a stable dose regimen of either of biguanide (BG) alone, BG + thiazolidinedione (TZD), BG + sulfonylurea (SU), or BG + TZD + SU for 90 days prior to study start Exclusion Criteria: Have received chronic (>14 consecutive days) systemic adrenocorticosteroid therapy by oral, intravenous, or intramuscular route or intraarticular steroid injection within 4 weeks prior to study start. Have been treated with drugs that promote weight loss within 90 days prior to study start. Have been treated with drugs that directly affect gastrointestinal motility for > 21 consecutive days within 90 days prior to study start. Have had prior exposure to exenatide BID or QW or participated in the clinical trial of exenatide BID or QW (including the case that the study drug was not administered). Have been treated for >2 consecutive weeks with any of the following excluded medications within 90 days prior to study start: Insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, GLP-1 analogs Have received treatment within 30 days prior to study start drug that has not received regulatory approval for any indication. Are currently enrolled in any other clinical study or participated in and completed the clinical study within 30 days prior to study start. Have donated blood within 30 days prior to study start.

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: exenatide once weekly<br> | Drug: exenatide once weekly<br>* subcutaneous injection, 2.0mg, once a week;<br>|
| Active Comparator: insulin glargine<br> | Drug: insulin glargine<br>* subcutaneous injection, titrated to achieve fasting serum glucose target, once a day<br>* Other names: insulin glargine-Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Endpoint (Week 26) | Change in HbA1c from baseline to endpoint (Week 26). | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving HbA1c<=7% | Percentage of subjects achieving HbA1c <=7.0% (for subjects with HbA1c >7% at baseline) | Baseline, Week 26 | 
| Percentage of Subjects Achieving HbA1c<=6.5% | Percentage of subjects achieving HbA1c <=6.5% (for subjects with HbA1c >6.5% at baseline) | Baseline, Week 26 | 
| Change in Fasting Serum Glucose (FSG) From Baseline to Endpoint (Week 26) | Change in FSG (centralized measurement) from baseline to endpoint (Week 26) | Baseline, Week 26 | 
| Change in Body Weight From Baseline to Endpoint (Week 26) | Change in Body Weight from baseline to endpoint (Week 26) | Baseline, Week 26 | 
| Change in Total Cholesterol From Baseline to Endpoint (Week 26) | Change in Total Cholesterol from baseline to endpoint (Week 26) | Baseline, Week 26 | 
| Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Endpoint (Week 26) | Change in HDL-C from baseline to endpoint (Week 26) | Baseline, Week 26 | 
| Ratio of Fasting Triglycerides at Endpoint (Week 26) to Baseline | Ratio of Triglycerides (measured in mg/dL) at endpoint (Week 26) to Baseline. Log(Postbaseline Triglycerides) - log(Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline. | Baseline, Week 26 | 
| Change in Blood Pressure From Baseline to Endpoint (Week 26) | Change in Blood Pressure from baseline to endpoint (Week 26) | Baseline, Week 26 | 
| Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events | Major confirmed hypoglycemia was defined as (1) any event accompanying symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure but resolved promptly in response to administration of glucagon or (2) glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring assistance because of severe impairment in consciousness or motor activity whether or not symptoms of hypoglycemia were felt by the patient. 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 postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS. | Baseline to Week 26 | 
| Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events | Minor confirmed hypoglycemia was defined as any event a patient felt that he or she was experiencing a sign or symptom associated with hypoglycemia that resolved by self-treatment or on its own, and a concurrent self-monitoring fingerstick 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 postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS. | 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; glargine; Lantus; Amylin; Lilly