A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Long-Acting Release(Once Weekly) to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00637273
• Other study ID #: BCB106 (DURATION - 2)
• Status: Completed
• Phase: Phase 3
• First received: March 6, 2008
• Last updated: March 19, 2015
• Start date: January 2008
• Est. completion date: July 2009

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 study will compare the benefits of exenatide once weekly treatment to those achieved by the approved antidiabetic therapies sitagliptin and pioglitazone in subjects whose type 2 diabetes is managed with metformin therapy alone. The safety and tolerability of the three treatment regimens will also be compared.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 514
• Est. completion date: July 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has been diagnosed with type 2 diabetes mellitus

• Has a hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at study start

• Has a body mass index (BMI)of 25 kg/m2 to 45 kg/m2, inclusive, at study start

• Has been on a stable treatment regimen of metformin for a minimum of 2 months prior to study start

• Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start:

1. Hormone replacement therapy (female subjects)

2. Oral contraceptives (female subjects)

3. Antihypertensive agents

4. Lipid-lowering agents

5. Thyroid replacement therapy

6. Antidepressant agents

7. Drugs known to affect body weight, including prescription medications (e.g. orlistat [XENICAL®], sibutramine [MERIDIA®], topiramate [TOPAMAX®]) and over-the-counter antiobesity agents

Exclusion Criteria:

• Has been previously exposed to exenatide once weekly

• Has donated blood within 60 days of study start or is planning to donate blood during the study

• Currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:

1. Exenatide (BYETTA®) or any Dipeptidyl peptidase-4 DPP-4)inhibitor, sulfonylurea (SU), thiazolidinedione (TZD), or glucagon-like peptide (GLP)-1 analog within 3 months prior to study start

2. Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start

3. Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start

4. Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption

5. Drugs interacting with the CYP2C8 enzyme system, including gemfibrozil (LOPID®) and rifampin

• Has received any investigational drug within 1 month (or five half-lives of investigational drug, whichever is greater) of study start

• Has previously experienced a clinically significant adverse event (e.g., significant edema) related to TZD or DPP-4 inhibitor use

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide once weekly
subcutaneous injection, 2.0mg, once a week
• sitagliptin
oral tablet, 100mg, once a day
• pioglitazone
oral tablet, 45mg, once a day
• placebo tablet
oral tablet, once a day
• placebo once weekly
subcutaneous injection, once a week

Locations

Country	Name	City	State
India	Research Site	Bangalore
India	Research Site	Indore
India	Research Site	Karnal
India	Research Site	Mumbai
India	Research Site	Pune
Mexico	Research Site	Cuernavaca	Morelos
Mexico	Research Site	Guadalajara	Jalisco
Mexico	Research Site	Mexico City	Distrito Federal
Mexico	Research Site	Monterrey	NuevoLeon
Mexico	Research Site	Toluca
Mexico	Research Site	Zapopan	Jalisco
United States	Research Site	Artesia	California
United States	Research Site	Athens	Ohio
United States	Research Site	Austin	Texas
United States	Research Site	Avon	Indiana
United States	Research Site	Baton Rouge	Louisiana
United States	Research Site	Boston	Massachusetts
United States	Research Site	Butte	Montana
United States	Research Site	Chelsea	Michigan
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Concord	California
United States	Research Site	Coral Gables	Florida
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Decatur	Georgia
United States	Research Site	Deland	Florida
United States	Research Site	Durham	North Carolina
United States	Research Site	Encino	California
United States	Research Site	Greenbrae	California
United States	Research Site	La Mesa	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Melbourne	Florida
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	New Hyde Park	New York
United States	Research Site	New Orleans	Louisiana
United States	Research Site	New Port Richey	Florida
United States	Research Site	New Windsor	New York
United States	Research Site	New York	New York
United States	Research Site	Olympia	Washington
United States	Research Site	Orange	California
United States	Research Site	Oxon Hill	Maryland
United States	Research Site	Paducah	Kentucky
United States	Research Site	Peoria	Arizona
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Richmond	Virginia
United States	Research Site	Rochester	New York
United States	Research Site	San Antonio	Texas
United States	Research Site	Spokane	Washington
United States	Research Site	St. Louis	Missouri
United States	Research Site	St. Louis Park	Minnesota
United States	Research Site	Statesville	North Carolina
United States	Research Site	Tacoma	Washington
United States	Research Site	Walnut Creek	California
United States	Research Site	Washington	District of Columbia
United States	Research Site	Whittier	California
United States	Research Site	Wichita	Kansas
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Ypsilanti	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  India,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Week 26	Absolute change in HbA1c from baseline (Day 1) to Week 26 [Week 26 - Baseline].	Day 1, Week 26	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <7% at Week 26	Percentages of subjects achieving HbA1c target values of <7% at Week 26.	Week 26	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26	Percentages of subjects achieving HbA1c target values of <=6.5% at Week 26.	Week 26	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26	Percentages of subjects achieving HbA1c target values of <=6.0% at Week 26.	Week 26	No
Secondary	Change in Body Weight From Baseline to Week 26	Change in body weight from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Week 26	Change in fasting plasma glucose from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Change in Systolic Blood Pressure From Baseline to Week 26	Change in systolic blood pressure from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Change in Diastolic Blood Pressure From Baseline to Week 26	Change in diastolic blood pressure from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Change in Fasting Total Cholesterol From Baseline to Week 26	Change in fasting total cholesterol from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26	Change in fasting HDL from baseline (Day 1) to Week 26.	Day 1, Week 26	No
Secondary	Ratio of Fasting Triglycerides at Week 26 to Baseline	Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.	Day 1, Week 26	No
Secondary	Assessment on Event Rate of Treatment-emergent Hypoglycemic Events	Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration < 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration < 54 mg/dL prior to treatment and not classified as major hypoglycemia.	Day 1 to Week 26	Yes