A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2)

NCT00637273 | Completed Phase 3 Results

• 1 other identifier: BCB106 (DURATION - 2)
• Study Type: interventional
• Target: 514
• Locations: 3 countries
• Sites: 62

Brief Summary

This study will compare the benefits of exenatide once weekly treatment to those achieved by the approved antidiabetic therapies sitagliptin and pioglitazone in subjects whose type 2 diabetes is managed with metformin therapy alone. The safety and tolerability of the three treatment regimens will also be compared.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; exenatide once weekly; Byetta; sitagliptin; Januvia; thiazolidinedione; Amylin; Lilly; Pioglitazone

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c From Baseline to Week 26

  Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\].

  Day 1, Week 26

Secondary Outcomes (11)

• Percentage of Subjects Achieving HbA1c Target of <7% at Week 26

  Week 26

• Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26

  Week 26

• Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26

  Week 26

• Change in Body Weight From Baseline to Week 26

  Day 1, Week 26

• Change in Fasting Plasma Glucose From Baseline to Week 26

  Day 1, Week 26

Study Arms (3)

1

EXPERIMENTAL

Drug: exenatide once weekly; Drug: placebo tablet

2

ACTIVE COMPARATOR

Drug: sitagliptin; Drug: placebo once weekly

3

ACTIVE COMPARATOR

Drug: pioglitazone; Drug: placebo once weekly

Interventions

exenatide once weekly DRUG

subcutaneous injection, 2.0mg, once a week

1

sitagliptin DRUG

oral tablet, 100mg, once a day

Also known as: Januvia

2

pioglitazone DRUG

oral tablet, 45mg, once a day

3

placebo tablet DRUG

oral tablet, once a day

1

placebo once weekly DRUG

subcutaneous injection, once a week

2; 3

Eligibility Criteria

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

You may qualify if:

• Has been diagnosed with type 2 diabetes mellitus
• Has a hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at study start
• Has a body mass index (BMI)of 25 kg/m2 to 45 kg/m2, inclusive, at study start
• Has been on a stable treatment regimen of metformin for a minimum of 2 months prior to study start
• 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 study start:
• 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

You may not qualify if:

• Has been previously exposed to exenatide once weekly
• Has donated blood within 60 days of study start or is planning to donate blood during the study
• Currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:
• Exenatide (BYETTA®) or any Dipeptidyl peptidase-4 DPP-4)inhibitor, sulfonylurea (SU), thiazolidinedione (TZD), or glucagon-like peptide (GLP)-1 analog within 3 months prior to study start
• Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start
• Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start
• 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
• Drugs interacting with the CYP2C8 enzyme system, including gemfibrozil (LOPID®) and rifampin
• Has received any investigational drug within 1 month (or five half-lives of investigational drug, whichever is greater) of study start
• Has previously experienced a clinically significant adverse event (e.g., significant edema) related to TZD or DPP-4 inhibitor use

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (62)

Research Site

Peoria, Arizona, United States

Location

Research Site

Artesia, California, United States

Location

Research Site

Concord, California, United States

Location

Research Site

Encino, California, United States

Location

Research Site

Greenbrae, California, United States

Location

Research Site

La Mesa, California, United States

Location

Research Site

Orange, California, United States

Location

Research Site

Walnut Creek, California, United States

Location

Research Site

Whittier, California, United States

Location

Research Site

Colorado Springs, Colorado, United States

Location

Research Site

Washington D.C., District of Columbia, United States

Location

Research Site

Coral Gables, Florida, United States

Location

Research Site

DeLand, Florida, United States

Location

Research Site

Melbourne, Florida, United States

Location

Research Site

Miami, Florida, United States

Location

Research Site

New Port Richey, Florida, United States

Location

Research Site

Decatur, Georgia, United States

Location

Research Site

Avon, Indiana, United States

Location

Research Site

Wichita, Kansas, United States

Location

Research Site

Paducah, Kentucky, United States

Location

Research Site

Baton Rouge, Louisiana, United States

Location

Research Site

New Orleans, Louisiana, United States

Location

Research Site

Oxon Hill, Maryland, United States

Location

Research Site

Boston, Massachusetts, United States

Location

Research Site

Chelsea, Michigan, United States

Location

Research Site

Ypsilanti, Michigan, United States

Location

Research Site

Saint Louis Park, Minnesota, United States

Location

Research Site

St Louis, Missouri, United States

Location

Research Site

Butte, Montana, United States

Location

Research Site

Lincoln, Nebraska, United States

Location

Research Site

Las Vegas, Nevada, United States

Location

Research Site

New Hyde Park, New York, United States

Location

Research Site

New Windsor, New York, United States

Location

Research Site

New York, New York, United States

Location

Research Site

Rochester, New York, United States

Location

Research Site

Durham, North Carolina, United States

Location

Research Site

Statesville, North Carolina, United States

Location

Research Site

Winston-Salem, North Carolina, United States

Location

Research Site

Athens, Ohio, United States

Location

Research Site

Cincinnati, Ohio, United States

Location

Research Site

Dayton, Ohio, United States

Location

Research Site

Philadelphia, Pennsylvania, United States

Location

Research Site

Rapid City, South Dakota, United States

Location

Research Site

Memphis, Tennessee, United States

Location

Research Site

Austin, Texas, United States

Location

Research Site

Dallas, Texas, United States

Location

Research Site

San Antonio, Texas, United States

Location

Research Site

Richmond, Virginia, United States

Location

Research Site

Olympia, Washington, United States

Location

Research Site

Spokane, Washington, United States

Location

Research Site

Tacoma, Washington, United States

Location

Research Site

Bangalore, India

Location

Research Site

Indore, India

Location

Research Site

Karnāl, India

Location

Research Site

Mumbai, India

Location

Research Site

Pune, India

Location

Research Site

Guadalajara, Jalisco, Mexico

Location

Research Site

Zapopan, Jalisco, Mexico

Location

Research Site

Mexico City, Mexico City, Mexico

Location

Research Site

Cuernavaca, Morelos, Mexico

Location

Research Site

Monterrey, NuevoLeon, Mexico

Location

Research Site

Toluca, State of Mexico, Mexico

Location

Related Publications (8)

• Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.

  PMID: 32306296 DERIVED

• Malloy J, Meloni A, Han J. Efficacy and tolerability of exenatide once weekly versus sitagliptin in patients with type 2 diabetes mellitus: a retrospective analysis of pooled clinical trial data. Postgrad Med. 2013 May;125(3):58-67. doi: 10.3810/pgm.2013.05.2661.

  PMID: 23748507 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

• Meloni AR, DeYoung MB, Han J, Best JH, Grimm M. Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals. Cardiovasc Diabetol. 2013 Mar 23;12:48. doi: 10.1186/1475-2840-12-48.

  PMID: 23522121 DERIVED

• 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.

  PMID: 23039868 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

• Wysham C, Bergenstal R, Malloy J, Yan P, Walsh B, Malone J, Taylor K. DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide. Diabet Med. 2011 Jun;28(6):705-14. doi: 10.1111/j.1464-5491.2011.03301.x.

  PMID: 21434995 DERIVED

• Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Aug 7;376(9739):431-9. doi: 10.1016/S0140-6736(10)60590-9. Epub 2010 Jun 26.

  PMID: 20580422 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Sitagliptin Phosphate; Pioglitazone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Peter Ohman, Medical Science Director
• 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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 17, 2008
• Study Start: January 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: July 1, 2009
• Last Updated: April 7, 2015
• Results First Posted: June 19, 2012

Record last verified: 2015-03

Locations

ME (6); IN (5); US (51)