Clinical trial NCT00877890: A Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly in Subjects With Type 2 Diabetes Mellitus (DURATION-5)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
exenatide once weekly
Byetta
Amylin
Lilly
Bydureon
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2009-04-08
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 24
timeFrame: Day 1, Week 24
Secondary outcomes:
measure: Percentage of Subjects Achieving HbA1c Target of <7%
timeFrame: Week 24
measure: Percentage of Subjects Achieving HbA1c Target of <=6.5%
timeFrame: Week 24
measure: Change in Fasting Plasma Glucose From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Percentage of Subjects Achieving Fasting Plasma Glucose Target of <=126 mg/dL
timeFrame: Week 24
measure: Change in Body Weight From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Change in Sitting Systolic Blood Pressure From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Change in Sitting Diastolic Blood Pressure From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Change in Total Cholesterol From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Change in High-density Lipoprotein (HDL) From Baseline to Week 24
timeFrame: Day 1, Week 24
measure: Ratio of Triglycerides at Week 24 to Baseline
timeFrame: Day 1, Week 24
measure: Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
timeFrame: Day 1 to Week 24
measure: Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
timeFrame: Day 1 to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Artesia
country: United States
facility: Research Site
state: California
city: Concord
country: United States
facility: Research Site
state: California
city: Encino
country: United States
facility: Research Site
state: California
city: Greenbrae
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: DeLand
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: New Port Richey
country: United States
facility: Research Site
state: Florida
city: Palm Harbor
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Avon
country: United States
facility: Research Site
state: Indiana
city: Evansville
country: United States
facility: Research Site
state: Indiana
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Paducah
country: United States
facility: Research Site
state: Kentucky
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Edina
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Butte
country: United States
facility: Research Site
state: Montana
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Raleigh
country: United States
facility: Research Site
state: North Carolina
city: Statesville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Delaware
country: United States
facility: Research Site
state: Ohio
city: Mentor
country: United States
facility: Research Site
state: Ohio
city: Eugene
country: United States
facility: Research Site
state: Oregon
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Austin
country: United States
facility: Research Site
state: Texas
city: Corpus Christi
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Burke
country: United States
facility: Research Site
state: Virginia
city: Manassas
country: United States
facility: Research Site
state: Virginia
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Lisa Porter, MD
role: STUDY_DIRECTOR
References:
citation: 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 Endocrinol Metab. 2011 May;96(5):1301-10. doi: 10.1210/jc.2010-2081. Epub 2011 Feb 9.
citation: Blevins T, Ruggles J, Hardy E. Onset of Glycemic and Weight Outcomes in Patients Initiating Exenatide Once Weekly: The Relationship of Exenatide Exposure with Efficacy over the First 24 Weeks of Treatment. Diabetes Ther. 2016 Jun;7(2):361-8. doi: 10.1007/s13300-016-0172-0. Epub 2016 May 5.
citation: Grimm M, Han J, Weaver C, Griffin P, Schulteis CT, Dong H, Malloy J. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013 May;125(3):47-57. doi: 10.3810/pgm.2013.05.2660.
citation: Peyrot M, Bushnell DM, Best JH, Martin ML, Cameron A, Patrick DL. Development and validation of the self-management profile for type 2 diabetes (SMP-T2D). Health Qual Life Outcomes. 2012 Oct 5;10:125. doi: 10.1186/1477-7525-10-125.
citation: 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.