A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5)

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Open-Label, Parallel-Group, Comparator-Controlled, Multicenter Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877890
• Other study ID #: BCB108 (DURATION-5)
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2009
• Last updated: March 19, 2015
• Start date: March 2009
• Est. completion date: January 2010

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 effects of commercially manufactured exenatide once weekly and exenatide BID in subjects whose type 2 diabetes is managed with diet and exercise alone or with oral antidiabetic medications. The study will examine glycemic control (as measured by HbA1C), safety, and tolerability.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: January 2010
• Est. primary completion date: October 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 hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at screening

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

• Has been treated with diet and exercise alone or in combination with a stable regimen of metformin (MET), a sulfonylurea (SU), a thiazolidinedione (TZD), a combination of metformin and an SU, a combination of metformin and a TZD, or a combination of an SU and a TZD for a minimum of 2 months prior to screening

• 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 screening:

• Hormone replacement therapy (female subjects)

• Oral contraceptives (female subjects)

• Antihypertensive agents

• Lipid-lowering agents

• Thyroid replacement therapy

• Antidepressant agents

• 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 ever been exposed to exenatide (exenatide once weekly [exenatide LAR], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) analog

• Has received any investigational drug within one month (or five half-lives of the investigational drug, whichever is greater) of screening

• Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications:

• Any dipeptidyl peptidase 4 (DPP-4) inhibitor within 3 months prior to screening

• Alpha glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of screening

• Insulin within 2 weeks of screening or for more than 1 week within 3 months of screening

• 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

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
• Type 2 Diabetes Mellitus

Intervention

Drug:
• exenatide once weekly
subcutaneous injection, 2.0mg, once a week
• exenatide twice daily
subcutaneous injection; 5mcg (4 weeks) and 10mcg (20 weeks); twice a day

Locations

Country	Name	City	State
United States	Research Site	Artesia	California
United States	Research Site	Austin	Texas
United States	Research Site	Avon	Indiana
United States	Research Site	Birmingham	Alabama
United States	Research Site	Burke	Virginia
United States	Research Site	Butte	Montana
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Concord	California
United States	Research Site	Corpus Christi	Texas
United States	Research Site	DeLand	Florida
United States	Research Site	Delaware	Ohio
United States	Research Site	Detroit	Michigan
United States	Research Site	Edina	Minnesota
United States	Research Site	Encino	California
United States	Research Site	Eugene	Oregon
United States	Research Site	Evansville	Indiana
United States	Research Site	Greenbrae	California
United States	Research Site	Hialeah	Florida
United States	Research Site	La Mesa	California
United States	Research Site	Lexington	Kentucky
United States	Research Site	Manassas	Virginia
United States	Research Site	Mentor	Ohio
United States	Research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	New Hyde Park	New York
United States	Research Site	New Port Richey	Florida
United States	Research Site	Olympia	Washington
United States	Research Site	Paducah	Kentucky
United States	Research Site	Palm Harbor	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Raleigh	North Carolina
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	Statesville	North Carolina
United States	Research Site	Tacoma	Washington
United States	Research Site	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (1)

Blevins T, Pullman J, Malloy J, Yan P, Taylor K, Schulteis C, Trautmann M, Porter L. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c From Baseline to Week 24	Change in HbA1c from baseline (Day 1) to Week 24 [Week 24 - Baseline].	Day 1, Week 24	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <7%	Percentages of subjects achieving HbA1c target value of <7% at Week 24.	Week 24	No
Secondary	Percentage of Subjects Achieving HbA1c Target of <=6.5%	Percentages of subjects achieving HbA1c target values of <=6.5% at Week 24.	Week 24	No
Secondary	Change in Fasting Plasma Glucose From Baseline to Week 24	Change in fasting plasma glucose from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL	Percentages of subjects achieving fasting plasma glucose target of <=126 mg/dL at Week 24.	Week 24	No
Secondary	Change in Body Weight From Baseline to Week 24	Change in body weight from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Change in Sitting Systolic Blood Pressure From Baseline to Week 24	Change in systolic blood pressure from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Change in Sitting Diastolic Blood Pressure From Baseline to Week 24	Change in diastolic blood pressure from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Change in Total Cholesterol From Baseline to Week 24	Change in total cholesterol from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Change in High-density Lipoprotein (HDL) From Baseline to Week 24	Change in HDL from baseline (Day 1) to Week 24.	Day 1, Week 24	No
Secondary	Ratio of Triglycerides at Week 24 to Baseline	Ratio of triglycerides (measured in mg/dL) at Week 24 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 24	No
Secondary	Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events	The major hypoglycemia category included 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 of less than 54 mg/dL prior to treatment, whether or not symptoms of hypoglycemia were perceived by the subject.	Day 1 to Week 24	Yes
Secondary	Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events	The minor hypoglycemia category included events in which symptoms consistent with hypoglycemia were accompanied by a blood glucose concentration of less than 54 mg/dL prior to treatment and not classified as major hypoglycemia.	Day 1 to Week 24	Yes