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

NCT ID: NCT00308139

Last Updated: 2015-08-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

303 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-04-30

Study Completion Date

2014-08-31

Brief Summary

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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

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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.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Exenatide Once Weekly

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

Group Type EXPERIMENTAL

exenatide, long acting release

Intervention Type DRUG

Exenatide Twice Daily

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.

Group Type ACTIVE_COMPARATOR

exenatide

Intervention Type DRUG

Interventions

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exenatide, long acting release

Intervention Type DRUG

exenatide

Intervention Type DRUG

Other Intervention Names

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BYDUREON Byetta

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lisa Porter, MD

Role: STUDY_DIRECTOR

Amylin Pharmaceuticals, LLC.

Locations

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Research Site 182

Encino, California, United States

Site Status

Research Site 171

La Jolla, California, United States

Site Status

Research Site 518

San Diego, California, United States

Site Status

Research Site 024

Walnut Creek, California, United States

Site Status

Research Site

Colorado Springs, Colorado, United States

Site Status

Research Site 057

Miami, Florida, United States

Site Status

Research Site

Chicago, Illinois, United States

Site Status

Research Site 149

Indianapolis, Indiana, United States

Site Status

Research Site 099

Lexington, Kentucky, United States

Site Status

Research Site 017

Detroit, Michigan, United States

Site Status

Research Site 224

Minneapolis, Minnesota, United States

Site Status

Research Site 312

St Louis, Missouri, United States

Site Status

Research Site 023

Butte, Montana, United States

Site Status

Research Site 053

Rochester, New York, United States

Site Status

Research Site 002

Durham, North Carolina, United States

Site Status

Research Site 123

Winston-Salem, North Carolina, United States

Site Status

Research Site 405

Cincinnati, Ohio, United States

Site Status

Research Site 557

Marion, Ohio, United States

Site Status

Research Site 231

Portland, Oregon, United States

Site Status

Research Site 152

Philadelphia, Pennsylvania, United States

Site Status

Research Site 587

Greer, South Carolina, United States

Site Status

Research Site 015

Dallas, Texas, United States

Site Status

Research Site 009

San Antonio, Texas, United States

Site Status

Research Site 108

Olympia, Washington, United States

Site Status

Research Site

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 30600137 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27525540 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25744115 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23748506 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23358123 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23166441 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22236356 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21529363 (View on PubMed)

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.

Reference Type DERIVED
PMID: 20215461 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18782641 (View on PubMed)

Other Identifiers

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MB001-010

Identifier Type: OTHER

Identifier Source: secondary_id

2993LAR-105 (DURATION - 1)

Identifier Type: -

Identifier Source: org_study_id

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