Effects of Exenatide Long-Acting Release on Glucose Control and Safety in Subjects With Type 2 Diabetes Mellitus(DURATION - 1)

NCT00308139 | Completed Phase 3 Results

• 2 other identifiers: 2993LAR-105 (DURATION - 1)MB001-010
• Study Type: interventional
• Target: 303
• Locations: 2 countries
• Sites: 25

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; exenatide; long acting release; LAR; Amylin; Lilly

Outcome Measures

Primary Outcomes (2)

• Change in HbA1c From Baseline to Week 30

  Absolute change in HbA1c from Baseline (Day -3) to Week 30 \[Week 30 - Baseline\]

  Day -3, Week 30

• 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)

  Measure by Geometric mean ratio (GMR) of plasma exenatide average steady state concentration Css,avg at Visit 11-14 to Visit 24-27 with 90% confidence interval

  Week 22

Secondary Outcomes (24)

• Change in HbA1c From Baseline to Week 364

  Day -3, Week 364

• Percentage of Subjects Achieving HbA1c Target of <7%

  Week 30

• Percentage of Subjects Achieving HbA1c Target of <7%

  Week 364

• Percentage of Subjects Achieving HbA1c Target of <=6.5%

  Week 30

• Percentage of Subjects Achieving HbA1c Target of <=6.5%

  Week 364

Study Arms (2)

Exenatide Once Weekly

EXPERIMENTAL

Subcutaneous injection (SC), once a week of long acting release (LAR) exenatide.

Drug: exenatide, long acting release

Exenatide Twice Daily

ACTIVE COMPARATOR

subcutaneous injection (SC), twice a day for the first 30 weeks, followed by exenatide LAR SC injection weekly for the remainder of the study. Sub-study: Exenatide 2 mg subcutaneous injection, Administered Using the Exenatide Once Weekly Single-Dose Tray , once a week for 11 visits, switch to Exenatide 2 mg subcutaneous injection, Administered Using the Dual chamber pen device. Exenatide 2mg SC injection administered using the Dual chamber pen device.

Drug: exenatide

Interventions

exenatide, long acting release DRUG

Also known as: BYDUREON

Exenatide Once Weekly

exenatide DRUG

Also known as: Byetta

Exenatide Twice Daily

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (25)

Research Site 182

Encino, California, 91436, United States

Location

Research Site 171

La Jolla, California, 92037, United States

Location

Research Site 518

San Diego, California, 92161, United States

Location

Research Site 024

Walnut Creek, California, 94598, United States

Location

Research Site

Colorado Springs, Colorado, United States

Location

Research Site 057

Miami, Florida, 33156, United States

Location

Research Site

Chicago, Illinois, United States

Location

Research Site 149

Indianapolis, Indiana, 46254, United States

Location

Research Site 099

Lexington, Kentucky, 40503, United States

Location

Research Site 017

Detroit, Michigan, 48202, United States

Location

Research Site 224

Minneapolis, Minnesota, 55416, United States

Location

Research Site 312

St Louis, Missouri, 63141, United States

Location

Research Site 023

Butte, Montana, 59701, United States

Location

Research Site 053

Rochester, New York, 14609, United States

Location

Research Site 002

Durham, North Carolina, 27713, United States

Location

Research Site 123

Winston-Salem, North Carolina, 27103, United States

Location

Research Site 405

Cincinnati, Ohio, 45219, United States

Location

Research Site 557

Marion, Ohio, 43302, United States

Location

Research Site 231

Portland, Oregon, 97239, United States

Location

Research Site 152

Philadelphia, Pennsylvania, 19146, United States

Location

Research Site 587

Greer, South Carolina, 29651, United States

Location

Research Site 015

Dallas, Texas, 75230, United States

Location

Research Site 009

San Antonio, Texas, 78229, United States

Location

Research Site 108

Olympia, Washington, 98502, United States

Location

Research Site

Toronto, Ontario, Canada

Location

Related Publications (10)

• 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.

  PMID: 30600137 DERIVED

• 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.

  PMID: 27525540 DERIVED

• 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.

  PMID: 25744115 DERIVED

• 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.

  PMID: 23748506 DERIVED

• 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.

  PMID: 23358123 DERIVED

• 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.

  PMID: 23166441 DERIVED

• 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.

  PMID: 22236356 DERIVED

• 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.

  PMID: 21529363 DERIVED

• 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.

  PMID: 20215461 DERIVED

• 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.

  PMID: 18782641 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: ClinicalTrialTransparency@astrazeneca.com
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Lisa Porter, MD

  Amylin Pharmaceuticals, LLC.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2006
• First Posted: March 29, 2006
• Study Start: April 1, 2006
• Primary Completion: July 1, 2008
• Study Completion: August 1, 2014
• Last Updated: August 26, 2015
• Results First Posted: August 17, 2012

Record last verified: 2015-07

Locations

US (24); CA (1)