An Evaluation of Exenatide and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus

Official Title: “An Evaluation of the Metabolic Effects of Exenatide, Rosiglitazone, and Exenatide Plus Rosiglitazone in Subjects With Type 2 Diabetes Mellitus Treated With Metformin”

This protocol is designed to evaluate the metabolic effects of adding exenatide, rosiglitazone, or both to an existing regimen of metformin in subjects with inadequate glycemic control.

Intervention(s) in this Clinical Trial

• Drug: exenatide
  • subcutaneous injection, 5mcg or 10mcg, twice a day
• Drug: rosiglitazone
  • oral tablet, 2mg or 4mg, twice a day

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Exenatide Arm
• Experimental: Exenatide plus Rosiglitazone Arm
• Experimental: Rosiglitazone Arm

Primary Measures

• Change in ASIiAUC During a Hyperglycemic Clamp Test.
  • Time Frame: 20 weeks
    Safety Issue?: No

Secondary Measures

• Change in AUC for Glucose During a Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Insulin Sensitivity Index as Measured by M-value.
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Insulin AUC in the First Stage From Baseline to Endpoint.
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Insulin iAUC From Baseline to Endpoint.
  • Time Frame: Week 20
    Safety Issue?: No
• Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in AUC for C-peptide During a Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT).
  • Time Frame: Week 20
    Safety Issue?: No
• Change in HbA1c
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting Serum Glucose Concentration.
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting C-peptide
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting Insulin
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting Proinsulin
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Body Weight
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting Total Cholesterol.
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting HDL Cholesterol
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting LDL Cholesterol
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Fasting Triglycerides
  • Time Frame: Week 20
    Safety Issue?: No
• Change in Percent Body Fat During a Meal Challenge Test (MCT)
  • Time Frame: 20 weeks
    Safety Issue?: No
• Change in Body Fat Mass During a Meal Challenge Test (MCT)
  • Time Frame: 20 weeks
    Safety Issue?: No
• Change in Lean Body Mass During a Meal Challenge Test (MCT)
  • Time Frame: 20 weeks
    Safety Issue?: No
• Change in Waist Circumference
  • Time Frame: 20 weeks
    Safety Issue?: No
• Change in Hip Circumference
  • Time Frame: 20 weeks
    Safety Issue?: No
• Change in Waist-to-hip Ratio
  • Time Frame: 20 weeks
    Safety Issue?: No
• Incidence of Hypoglycemia Events
  • Time Frame: 20 weeks
    Safety Issue?: No
• Hypoglycemia Rate Per 30 Days Per Patient
  • Time Frame: 20 weeks
    Safety Issue?: No
• Pedal Edema Score
  • Time Frame: 20 weeks
    Safety Issue?: No

Inclusion Criteria:

• HbA1c of 6.8% to 10.0%, inclusive.
• Body mass index (BMI) of 25 kg/m^2 to 40 kg/m^2, inclusive.

Exclusion Criteria:

• Have participated in this study previously, or have received exenatide, pramlintide acetate, GLP-1 analogs, or dipeptidyl peptidase-IV (DPP-IV) inhibitors
• Have participated in an interventional, medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of study start. This criterion includes drugs that have not received regulatory approval for any indication at the time of study start.
• Treated with any of the following medications:
• Thiazolidinedione within 5 months of screening;
• Sulfonylurea within 3 months of screening;
• Metformin/sulfonylurea combination therapy within 3 months of screening;
• Alpha-glucosidase inhibitor within 3 months of screening;
• Meglitinide within 3 months of screening;
• Insulin for more than 1 week within the 3 months prior to screening.
• Symlin (pramlintide acetate) injection or Byetta (exenatide) injection at any time
• Chronic (more than 2 weeks) or recent (within 4 weeks of study start) use of a drug that directly affects gastrointestinal motility
• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding study start
• Regular use of a medication with addictive potential such as an opiate, narcotic, or tranquilizer
• Systemic antineoplastic agent
• Systemic transplantation medication
• Drugs for weight loss, including over-the-counter medications, within the 4 months prior to study start

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Amylin Pharmaceuticals, Inc. Industry

Overall Clinical Trial Officials and Contacts

James Malone, MD Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00135330

Study ID Number: H8O-US-GWAY

ClinicalTrials.gov Identifier: NCT00135330

Health Authority: United States: Food and Drug Administration