Clinical trial NCT00308139: Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus(DURATION - 1)
Official title: A Randomized, Open-Label, Multicenter, Comparator-Controlled Study to Examine the Effects of Exenatide Long-Acting Release on Glucose Control (HbA1c) and Safety in Subjects With Type 2 Diabetes Mellitus Managed With Diet Modification and Exercise and/or Oral Antidiabetic Medications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
exenatide
long acting release
LAR
Amylin
Lilly
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2006-03-29
Enrollment: 303
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Randomized, Open-Label, Multicenter, Comparator-Controlled Study to Examine the Effects of Exenatide Long-Acting Release (LAR) on Glucose Control (HbA1c) and Safety in Subjects with Type 2 Diabetes Mellitus Managed with Diet Modification and Exercise and/or Oral Antidiabetic Medications.

Detailed description: This trial is designed to examine the effect of exenatide once weekly compared to exenatide twice daily on glucose control and safety in subjects for at least 30 weeks. The study is also designed to examine glucose control during the transition from exenatide twice daily for 30 weeks to exenatide once weekly. Long-term safety and efficacy will be monitored during the open-ended assessment periods. This study will be conducted in approximately 300 subjects with type 2 diabetes treated with diet modification and exercise alone or in combination with a stable regimen of metformin, SU, thiazolidinedione (TZD), a combination of metformin and SU, a combination of metformin and TZD, or a combination of SU and TZD.

Eligibility criteria: Inclusion Criteria:

* Has type 2 diabetes mellitus treated with diet modification and exercise alone or in combination with a stable regimen of a combination of metformin, sulphonylureas, and thiazolidinediones for a minimum of 2 months at screening.
* Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
* Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.
* (For sub-study) Currently participating in open ended assessment period of main study 2993 LAR105

Exclusion Criteria:

* Has been previously exposed to exenatide (Byetta®), exenatide LAR, or any glucagon-like peptide-1 (GLP-1) analog.
* Received any investigational drug or has participated in any type of clinical trial within 30 days prior to screening.
* Has been treated, is currently treated, or is expected to require or undergo treatment with any of the following excluded medications:

  * Alpha glucosidase inhibitor or meglitinide within 30 days of screening;
  * Insulin within 2 weeks prior to screening or insulin for longer than 1 week within 3 months of screening;
  * Regular use (\> 14 days) of drugs that directly affect gastrointestinal motility;
  * Regular use (\> 14 days) of systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption;
  * Regular use (\> 14 days) of medications with addictive potential such as opiates and opioids;
  * Prescription or over-the-counter weight loss medications within 6 months of screening.
* (For sub-study) Subjects will be terminated from study who do not participate in the dual chamber pen substudy

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Sub-study Relative Bioavailability of Exenatide When Administered Using the Exenatide Once Weekly Dual Chambered Pen and the Exenatide Once Weekly Single Dose Tray (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen-11 Weekly Dose)
timeFrame: Week 22
Secondary outcomes:
measure: Change in HbA1c From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Percentage of Subjects Achieving HbA1c Target of <7%
timeFrame: Week 30
measure: Percentage of Subjects Achieving HbA1c Target of <7%
timeFrame: Week 364
measure: Percentage of Subjects Achieving HbA1c Target of <=6.5%
timeFrame: Week 30
measure: Percentage of Subjects Achieving HbA1c Target of <=6.5%
timeFrame: Week 364
measure: Percentage of Subjects Achieving HbA1c Target of <=6.0%
timeFrame: Week 30
measure: Exenatide LAR Steady State Concentration From Week 29 to Week 30
timeFrame: Week 29 to Week 30
measure: Change in 2 Hours (2h) Postprandial Glucose From Baseline to Week 14
timeFrame: Day -3, Week 14
measure: Sub-study Safety and Tolerability of Exenatide When Administered Using the Once Weekly Single Dose Tray and the Once Weekly Dual (Single Dose Tray-11 Weekly Doses Switch to Dual Chamber Pen-11 Weekly Dose)
timeFrame: Week 22
measure: Change in Body Weight From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Change in Body Weight From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Change in Fasting Plasma Glucose From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Change in Fasting Plasma Glucose From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Change in Blood Pressure From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Change in Blood Pressure From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Change in Total Cholesterol From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Change in Total Cholesterol From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 30
timeFrame: Day -3, Week 30
measure: Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Week 364
timeFrame: Day -3, Week 364
measure: Ratio of Triglycerides at Week 30 to Baseline
timeFrame: Day -3, Week 30
measure: Ratio of Triglycerides at Week 364 to Baseline
timeFrame: Day -3, Week 364
measure: Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With SU Use at Screening
timeFrame: Day 1 to Week 364
measure: Assessment on Event Rate of Treatment-emergent Hypoglycemic Events With Non-SU Use at Screening
timeFrame: Day 1 to Week 364
Other outcomes:
Locations:
city: Encino
country: United States
facility: Research Site 182
state: California
city: La Jolla
country: United States
facility: Research Site 171
state: California
city: San Diego
country: United States
facility: Research Site 518
state: California
city: Walnut Creek
country: United States
facility: Research Site 024
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Miami
country: United States
facility: Research Site 057
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Research Site 149
state: Indiana
city: Lexington
country: United States
facility: Research Site 099
state: Kentucky
city: Detroit
country: United States
facility: Research Site 017
state: Michigan
city: Minneapolis
country: United States
facility: Research Site 224
state: Minnesota
city: St. Louis
country: United States
facility: Research Site 312
state: Missouri
city: Butte
country: United States
facility: Research Site 023
state: Montana
city: Rochester
country: United States
facility: Research Site 053
state: New York
city: Durham
country: United States
facility: Research Site 002
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site 123
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site 405
state: Ohio
city: Marion
country: United States
facility: Research Site 557
state: Ohio
city: Portland
country: United States
facility: Research Site 231
state: Oregon
city: Philadelphia
country: United States
facility: Research Site 152
state: Pennsylvania
city: Greer
country: United States
facility: Research Site 587
state: South Carolina
city: Dallas
country: United States
facility: Research Site 015
state: Texas
city: San Antonio
country: United States
facility: Research Site 009
state: Texas
city: Olympia
country: United States
facility: Research Site 108
state: Washington
city: Toronto
country: Canada
facility: Research Site
state: Ontario
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Lisa Porter, MD
role: STUDY_DIRECTOR
References:
citation: Philis-Tsimikas A, Wysham CH, Hardy E, Han J, Iqbal N. Efficacy and tolerability of exenatide once weekly over 7 years in patients with type 2 diabetes: An open-label extension of the DURATION-1 study. J Diabetes Complications. 2019 Mar;33(3):223-230. doi: 10.1016/j.jdiacomp.2018.11.012. Epub 2018 Dec 5.
citation: Henry RR, Klein EJ, Han J, Iqbal N. Efficacy and Tolerability of Exenatide Once Weekly Over 6 Years in Patients with Type 2 Diabetes: An Uncontrolled Open-Label Extension of the DURATION-1 Study. Diabetes Technol Ther. 2016 Nov;18(11):677-686. doi: 10.1089/dia.2016.0107. Epub 2016 Aug 15.
citation: Wysham CH, MacConell LA, Maggs DG, Zhou M, Griffin PS, Trautmann ME. Five-year efficacy and safety data of exenatide once weekly: long-term results from the DURATION-1 randomized clinical trial. Mayo Clin Proc. 2015 Mar;90(3):356-65. doi: 10.1016/j.mayocp.2015.01.008.
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: Macconell L, Pencek R, Li Y, Maggs D, Porter L. Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years. Diabetes Metab Syndr Obes. 2013;6:31-41. doi: 10.2147/DMSO.S35801. Epub 2013 Jan 21.
citation: Chiquette E, Toth PP, Ramirez G, Cobble M, Chilton R. Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers. Vasc Health Risk Manag. 2012;8:621-9. doi: 10.2147/VHRM.S37969. Epub 2012 Nov 12.
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.
citation: Taylor K, Gurney K, Han J, Pencek R, Walsh B, Trautmann M. Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years. BMC Endocr Disord. 2011 Apr 29;11:9. doi: 10.1186/1472-6823-11-9.
citation: Buse JB, Drucker DJ, Taylor KL, Kim T, Walsh B, Hu H, Wilhelm K, Trautmann M, Shen LZ, Porter LE; DURATION-1 Study Group. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010 Jun;33(6):1255-61. doi: 10.2337/dc09-1914. Epub 2010 Mar 9.
citation: Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L; DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008 Oct 4;372(9645):1240-50. doi: 10.1016/S0140-6736(08)61206-4. Epub 2008 Sep 7.