An Evaluation of Exenatide and Rosiglitazone in Subjects With Type 2 Diabetes Mellitus - Full Text View

Purpose

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.

Condition	Intervention	Phase
Diabetes Mellitus, Type 2	Drug: exenatide Drug: rosiglitazone	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Rosiglitazone Exenatide Rosiglitazone Maleate

U.S. FDA Resources

Further study details as provided by Amylin Pharmaceuticals, LLC.:

Primary Outcome Measures:

Change in ASIiAUC During a Hyperglycemic Clamp Test. [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in insulin incremental area under the concentration-time curve (ASIiAUC) from baseline to week 20. ASIiAUC is a measure of beta-cell function.

Secondary Outcome Measures:

Change in AUC for Glucose During a Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in AUC(15-180 min) for glucose during a MCT baseline to week 20.
Change in Insulin Sensitivity Index as Measured by M-value. [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change of M-Value (mg/kg-min) during hyperinsulinemic euglycemic clamp test from baseline to week 20.
Change in Insulin AUC in the First Stage From Baseline to Endpoint. [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
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.
Change in Insulin iAUC From Baseline to Endpoint. [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
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.
Ratio (Value at Endpoint Divided by Value at Baseline) of AUC for Insulin During a Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Ratio (value at endpoint divided by value at baseline) of AUC (15-180 min) for insulin (uIU-min/ml) during MCT.
Change in AUC for C-peptide During a Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
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.
Change in Incremental for Postprandial Glucose During a Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in incremental for postprandial glucose (mmol/L) during a MCT from baseline to week 20.
Change in Incremental for Postprandial Insulin During Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in incremental for postprandial insulin (mmol/L) during meal challenge test (MCT) from baseline to week 20.
Change in Incremental for Postprandial C-peptide During Meal Challenge Test (MCT). [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in incremental for postprandial C-peptide (mmol/L) during MCT from baseline to week 20.
Change in HbA1c [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in HbA1c from baseline to week 20.
Change in Fasting Serum Glucose Concentration. [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting serum glucose concentration from baseline to week 20.
Change in Fasting C-peptide [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting C-peptide from baseline to week 20.
Change in Fasting Insulin [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting insulin from baseline to week 20.
Change in Fasting Proinsulin [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline
Change in Body Weight [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in body weight from baseline to week 20.
Change in Fasting Total Cholesterol. [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting total cholestrol from baseline to week 20.
Change in Fasting HDL Cholesterol [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20.
Change in Fasting LDL Cholesterol [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20.
Change in Fasting Triglycerides [ Time Frame: Week 20 ] [ Designated as safety issue: No ]
Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20.
Change in Percent Body Fat During a Meal Challenge Test (MCT) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in percent body fat from baseline to week 20, as assessed during an MCT
Change in Body Fat Mass During a Meal Challenge Test (MCT) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in body fat mass form baseline to week 20, as assessed during an MCT
Change in Lean Body Mass During a Meal Challenge Test (MCT) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in lean body mass from baseline to week 20, as assessed during an MCT
Change in Waist Circumference [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in waist circumference from baseline to week 20
Change in Hip Circumference [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in hip circumference form baseline to week 20
Change in Waist-to-hip Ratio [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Change in waist-to-hip ratio (waist circumference divided by hip circumference) from baseline to week 20
Incidence of Hypoglycemia Events [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Number of subjects experiencing hypoglycemia at any point during the study
Hypoglycemia Rate Per 30 Days Per Patient [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Average number of episodes of hypoglycemia per 30 days per patient
Pedal Edema Score [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
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.)

Enrollment:	137
Study Start Date:	October 2005
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Exenatide Arm	Drug: exenatide subcutaneous injection, 5mcg or 10mcg, twice a day Other Name: Byetta
Experimental: Exenatide plus Rosiglitazone Arm	Drug: exenatide subcutaneous injection, 5mcg or 10mcg, twice a day Other Name: Byetta Drug: rosiglitazone oral tablet, 2mg or 4mg, twice a day Other Name: Avandia
Experimental: Rosiglitazone Arm	Drug: rosiglitazone oral tablet, 2mg or 4mg, twice a day Other Name: Avandia

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00135330

Locations

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

Sponsors and Collaborators

Amylin Pharmaceuticals, LLC.

Eli Lilly and Company

Investigators

Study Director:

James Malone, MD

Eli Lilly and Company

More Information

No publications provided by Amylin Pharmaceuticals, LLC.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Jan 27.

Responsible Party:	Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:	NCT00135330 History of Changes
Other Study ID Numbers:	H8O-US-GWAY
Study First Received:	August 24, 2005
Results First Received:	July 21, 2009
Last Updated:	February 26, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Amylin Pharmaceuticals, LLC.:

diabetes
exenatide
rosiglitazone
Amylin
Lilly

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Exenatide
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013