Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Study Overview
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Brief Summary
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This is a multicenter, comparator-controlled, open-label, randomized, two-arm, parallel trial to compare the effect of exenatide twice daily and insulin glargine on glycemic control, as measured by hemoglobin A1c (HbA1c).

Official Title
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Effect of AC2993 (Synthetic Exendin-4) Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Exenatide (AC2993)
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have been treated with a stable dose of one of the following for at least 3 months prior to screening: 1. 1500 to 2550 mg/day immediate-release metformin (or 1500 to 2000 mg/day extended-release metformin) and at least an optimally effective dose of a sulfonylurea, or 2. a fixed-dose sulfonylurea/metformin combination therapy with the same sulfonylurea and metformin requirements as for the individual components. HbA1c between 7.0% and 10.0%, inclusive. History of stable body weight (not varying by >10% for at least three months prior to screening). Female patients are not breastfeeding, and female patients of childbearing potential (not surgically sterilized and between menarche and 1-year postmenopause) Exclusion Criteria: Patients are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Patients are employed by Lilly or Amylin. Patients have participated in this study previously or any other study using AC2993 or GLP-1 analogs. Patients have participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to screening. This criterion includes drugs that have not received regulatory approval for any indication at the time of study entry. Patients have had greater than three episodes of severe hypoglycemia within 6 months prior to screening. Patients are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer. Patients have cardiac disease that is Class III or IV, according to the New York Heart Association criteria. Patients have a known allergy or hypersensitivity to insulin glargine, AC2993, or excipients contained in these agents. Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label, in the opinion of the investigator. Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.3 mg/dL for females. Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamicpyruvic transaminase greater than three times the upper limit of the reference range. Patients have known hemoglobinopathy or chronic anemia. Patients are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to screening. Patients have used any prescription drug to promote weight loss within 3 months prior to screening. Patients have any other condition (including known drug or alcohol abuse or psychiatric disorder) that precludes them from following and completing the protocol, in the opinion of the investigator. Patients fail to satisfy the investigator of suitability to participate for any other reason.

Ages Eligible for Study
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Minimum Age: 30 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>exenatide subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks | Drug: Exenatide (AC2993)<br>* subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 22 weeks<br>* Other names: Byetta;|
| Active Comparator: Insulin Glargine Arm<br>subcutaneous injection, once daily; forced titration to target blood glucose level | Drug: Insulin glargine<br>* subcutaneous injection, once daily; forced titration to target blood glucose level<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Hemoglobin (HbA1c) | 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 <=7% | Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 26 (percentage = [number of subjects with HbA1c <=7% at week 26 divided by number of subjects with HbA1c >7% at baseline] * 100%). | 26 weeks | 
| Change in Body Weight | Change in body weight from baseline to week 26 | Baseline, week 26 | 
| Change in Fasting Serum Glucose | Change in fasting serum glucose from baseline to week 26 | Baseline, week 26 | 
| Change in 7-point Self-monitored Blood Glucose (SMBG) Profile | Change in 7-point (pre-breakfast, 2 hour post breakfast, pre-lunch, 2 hour post lunch, pre-dinner, 2 hour post dinner, 0300 hours) SMBG profile from baseline to week 26 | Baseline, week 26 | 
| Percentage of Patients With Hypoglycemic Events | Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study divided by the total number of patients who participated in the 26 week Parent Study | 26 weeks | 
| Change in Rate of Hypoglycemic Events | Change in rate of hypoglycemic events per 30 days per patient from baseline to week 26 | Baseline, week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Insulin glargine, comparator, Amylin, Lilly