Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

Study Overview
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Brief Summary
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This is a Phase 3, multicenter, open-label, comparator-controlled trial comparing the effect of exenatide twice daily to twice daily biphasic insulin aspart on glycemic control, as measured by hemoglobin A1c (HbA1c).

Official Title
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Efficacy of Exenatide (AC2993, Synthetic Exendin-4, LY2148568) Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: exenatide
* Drug: biphasic insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have been treated with a stable dose of the following for at least 3 months prior to screening: 1. >=1500 mg/day immediate-release metformin or extended-release metformin and at least an optimally effective dose for brand of 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 11.0%, inclusive. Patients have a body mass index >25kg/m2 and <40 kg/m2. Female patients are not breastfeeding, and female patients of childbearing potential test negative for pregnancy, do not intend to become pregnant during the study, and agree to continue using a reliable method of birth control 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 previously, in this or any other study, received exenatide or glucagon-like peptide-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 have less than 5 years of remission history from any malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate 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 biphasic insulin aspart, exenatide, or excipients contained in these agents. Patients have characteristics contraindicating metformin or sulfonylurea use, according to product-specific label. Patients have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine >=1.5 mg/dL for males and >=1.2 mg/dL for females. Patients have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase/serum glutamic pyruvic transaminase greater than three times the upper limit of the reference range. Patients have known hemoglobinopathy or chronic anemia. Patients have active proliferative retinopathy or macular edema. Patients are receiving treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility, including but not limited to metoclopramide, cisapride, and chronic macrolide antibiotics. 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 been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: insulin, thiazolidinediones, alpha-glucosidase inhibitors, meglitinides. 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>subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks | Drug: exenatide<br>* subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks<br>* Other names: Byetta;|
| Active Comparator: Biphasic Insulin Aspart Arm<br>subcutaneous injection, twice daily; titration to target blood glucose level | Drug: biphasic insulin aspart<br>* subcutaneous injection, twice daily; titration to target blood glucose level<br>* Other names: NovoLog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glcosylated Hemoglobin (HbA1c) | Change in HbA1c from baseline to week 52 | baseline, week 52 | 

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 52 (percentage = [number of subjects with HbA1c <=7% at week 52 divided by number of subjects with HbA1c >7% at baseline] * 100%). | 52 weeks | 
| Change in Body Weight | Change in body weight from baseline to week 52. | baseline, week 52 | 
| Change in Fasting Serum Glucose | Change in fasting serum glucose from baseline to week 52 | baseline, week 52 | 
| Change in 7-point Self-monitored Blood Glucose (SMBG) Profile | Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52 | baseline, week 52 | 
| Percentage of Patients With Hypoglycemic Events | Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study | 52 weeks | 
| Change in Rate of Hypoglycemic Events | Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52 | baseline, week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exendin, Amylin, Lilly, insulin aspart