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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: exenatide; Drug: rosiglitazone

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Research Site
  • California
    • San Francisco, California, United States
      • Research Site
  • Florida
    • Jacksonville, Florida, United States
      • Research Site
    • Orlando, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
    • Pittsfield, Massachusetts, United States
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Research Site
    • Rochester, Minnesota, United States
      • Research Site
  • New York
    • Bronx, New York, United States
      • Research Site
    • Syracuse, New York, United States
      • Research Site
  • Ohio
    • Cincinatti, Ohio, United States
      • Research Site
  • Texas
    • League City, Texas, United States
      • Research Site
    • New Braunfels, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
  • Washington
    • Renton, Washington, United States
      • Research Site
    • Spokane, Washington, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exenatide Arm	Drug: exenatide; subcutaneous injection, 5mcg or 10mcg, twice a day; Other Names: Byetta
Experimental: Exenatide plus Rosiglitazone Arm	Drug: exenatide; subcutaneous injection, 5mcg or 10mcg, twice a day; Other Names: Byetta; Drug: rosiglitazone; oral tablet, 2mg or 4mg, twice a day; Other Names: Avandia
Experimental: Rosiglitazone Arm	Drug: rosiglitazone; oral tablet, 2mg or 4mg, twice a day; Other Names: Avandia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ASIiAUC During a Hyperglycemic Clamp Test.	Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function.	20 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in AUC for Glucose During a Meal Challenge Test (MCT).	Change in AUC(15-180 min) for glucose during a MCT baseline to week 20.	Week 20
Change in Insulin Sensitivity Index as Measured by M-value.	Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20.	Week 20
Change in Insulin AUC in the First Stage From Baseline to Endpoint.	Change in insulin AUC in the first stage(uIU-min/ml) from baseline to week 20. "First stage" represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.	Week 20
Change in Insulin iAUC From Baseline to Endpoint.	Change in insulin iAUC in the first stage(uIU-min/ml) from baseline to week 20. "First stage" represents the first 10 minutes after reaching a steady state during a hyperglycemic clamp test.	Week 20
Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT).	Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT.	Week 20
Change in AUC for C-peptide During a Meal Challenge Test (MCT).	Ratio (value at endpoint divided by value at baseline) of AUC(15-180 min) for C-peptide (nmol-min/L) during a MCT from baseline to week 20.	Week 20
Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT).	Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20.	Week 20
Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT).	Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20.	Week 20
Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT).	Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20.	Week 20
Change in HbA1c	Change in HbA1c from baseline to week 20.	Week 20
Change in Fasting Serum Glucose Concentration.	Change in fasting serum glucose concentration from baseline to week 20.	Week 20
Change in Fasting C-peptide	Change in fasting C-peptide from baseline to week 20.	Week 20
Change in Fasting Insulin	Change in fasting insulin from baseline to week 20.	Week 20
Change in Fasting Proinsulin	Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline	Week 20
Change in Body Weight	Change in body weight from baseline to week 20.	Week 20
Change in Fasting Total Cholesterol.	Change in fasting total cholestrol from baseline to week 20.	Week 20
Change in Fasting HDL Cholesterol	Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20.	Week 20
Change in Fasting LDL Cholesterol	Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20.	Week 20
Change in Fasting Triglycerides	Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20.	Week 20
Change in Percent Body Fat During a Meal Challenge Test (MCT)	Change in percent body fat from baseline to week 20, as assessed during an MCT	20 weeks
Change in Body Fat Mass During a Meal Challenge Test (MCT)	Change in body fat mass form baseline to week 20, as assessed during an MCT	20 weeks
Change in Lean Body Mass During a Meal Challenge Test (MCT)	Change in lean body mass from baseline to week 20, as assessed during an MCT	20 weeks
Change in Waist Circumference	Change in waist circumference from baseline to week 20	20 weeks
Change in Hip Circumference	Change in hip circumference form baseline to week 20	20 weeks
Change in Waist-to-hip Ratio	Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20	20 weeks
Incidence of Hypoglycemia Events	Number of subjects experiencing hypoglycemia at any point during the study	20 weeks
Hypoglycemia Rate Per 30 Days Per Patient	Average number of episodes of hypoglycemia per 30 days per patient	20 weeks
Pedal Edema Score	Pedal edema scores experienced by each patient throughout the study ("1+" indicates a patient experienced a pedal edema score of 1 , 2, or 3; "2+" indicates a patient experienced a pedal edema score of 2 or 3, etc.) Scale: Slight pitting, no visible distortion, disappears rapidly; A somewhat deeper pit than in 1+, but again no readily detectable distortion, and it disappears in 10 - 15 seconds; The pit is noticeably deep and may last more than a minute; the dependent extremity looks fuller and swollen; The pit is very deep, lasts as long as 2 - 5 minutes, and the dependent extremity is grossly distorted	20 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: James Malone, MD, Eli Lilly and Company

Publications and helpful links

General Publications

• Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.
• DeFronzo RA, Triplitt C, Qu Y, Lewis MS, Maggs D, Glass LC. Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin. Diabetes Care. 2010 May;33(5):951-7. doi: 10.2337/dc09-1521. Epub 2010 Jan 27.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: August 24, 2005
• First Submitted That Met QC Criteria: August 24, 2005
• First Posted (Estimate): August 26, 2005

Study Record Updates

• Last Update Posted (Estimate): April 7, 2015
• Last Update Submitted That Met QC Criteria: March 19, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: diabetes; exenatide; Lilly; Amylin; rosiglitazone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Rosiglitazone; Exenatide
• Other Study ID Numbers: H8O-US-GWAY