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

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135330
• Other study ID #: H8O-US-GWAY
• Status: Completed
• Phase: Phase 3
• First received: August 24, 2005
• Last updated: March 19, 2015
• Start date: October 2005
• Est. completion date: July 2008

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change in HbA1c	Change in HbA1c from baseline to week 20.	Week 20	No
Secondary	Change in Fasting Serum Glucose Concentration.	Change in fasting serum glucose concentration from baseline to week 20.	Week 20	No
Secondary	Change in Fasting C-peptide	Change in fasting C-peptide from baseline to week 20.	Week 20	No
Secondary	Change in Fasting Insulin	Change in fasting insulin from baseline to week 20.	Week 20	No
Secondary	Change in Fasting Proinsulin	Ratio (endpoint value divided by baseline value) for fasting proinsulin, comparing endpoint (week 20) to baseline	Week 20	No
Secondary	Change in Body Weight	Change in body weight from baseline to week 20.	Week 20	No
Secondary	Change in Fasting Total Cholesterol.	Change in fasting total cholestrol from baseline to week 20.	Week 20	No
Secondary	Change in Fasting HDL Cholesterol	Change in fasting high-density lipoprotein (HDL) cholesterol from baseline to week 20.	Week 20	No
Secondary	Change in Fasting LDL Cholesterol	Change in fasting low-density lipoprotein (LDL) cholesterol from baseline to week 20.	Week 20	No
Secondary	Change in Fasting Triglycerides	Ratio (endpint value divided by baseline value) of fasting triglycerides from baseline to week 20.	Week 20	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Change in Waist Circumference	Change in waist circumference from baseline to week 20	20 weeks	No
Secondary	Change in Hip Circumference	Change in hip circumference form baseline to week 20	20 weeks	No
Secondary	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	No
Secondary	Incidence of Hypoglycemia Events	Number of subjects experiencing hypoglycemia at any point during the study	20 weeks	No
Secondary	Hypoglycemia Rate Per 30 Days Per Patient	Average number of episodes of hypoglycemia per 30 days per patient	20 weeks	No
Secondary	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	No