Back to resultsA 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)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
exenatide once weekly
sitagliptin
pioglitazone
placebo tablet
placebo once weekly
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring diabetes, exenatide once weekly, Byetta, sitagliptin, Januvia, thiazolidinedione, Amylin, Lilly, Pioglitazone
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
1
2
3
Arm Description
Outcomes
Primary Outcome Measures
Change in HbA1c From Baseline to Week 26
Absolute change in HbA1c from baseline (Day 1) to Week 26 [Week 26 - Baseline].
Secondary Outcome Measures
Percentage of Subjects Achieving HbA1c Target of <7% at Week 26
Percentages of subjects achieving HbA1c target values of <7% at Week 26.
Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26
Percentages of subjects achieving HbA1c target values of <=6.5% at Week 26.
Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26
Percentages of subjects achieving HbA1c target values of <=6.0% at Week 26.
Change in Body Weight From Baseline to Week 26
Change in body weight from baseline (Day 1) to Week 26.
Change in Fasting Plasma Glucose From Baseline to Week 26
Change in fasting plasma glucose from baseline (Day 1) to Week 26.
Change in Systolic Blood Pressure From Baseline to Week 26
Change in systolic blood pressure from baseline (Day 1) to Week 26.
Change in Diastolic Blood Pressure From Baseline to Week 26
Change in diastolic blood pressure from baseline (Day 1) to Week 26.
Change in Fasting Total Cholesterol From Baseline to Week 26
Change in fasting total cholesterol from baseline (Day 1) to Week 26.
Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26
Change in fasting HDL from baseline (Day 1) to Week 26.
Ratio of Fasting Triglycerides at Week 26 to Baseline
Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration < 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration < 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Full Information
NCT ID
NCT00637273
First Posted
March 6, 2008
Last Updated
March 19, 2015
Sponsor
AstraZeneca
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00637273
Brief Title
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)
Official Title
A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Long-Acting Release(Once Weekly) to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
Collaborators
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
diabetes, exenatide once weekly, Byetta, sitagliptin, Januvia, thiazolidinedione, Amylin, Lilly, Pioglitazone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
514 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Active Comparator
Arm Title
3
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
exenatide once weekly
Intervention Description
subcutaneous injection, 2.0mg, once a week
Intervention Type
Drug
Intervention Name(s)
sitagliptin
Other Intervention Name(s)
Januvia
Intervention Description
oral tablet, 100mg, once a day
Intervention Type
Drug
Intervention Name(s)
pioglitazone
Intervention Description
oral tablet, 45mg, once a day
Intervention Type
Drug
Intervention Name(s)
placebo tablet
Intervention Description
oral tablet, once a day
Intervention Type
Drug
Intervention Name(s)
placebo once weekly
Intervention Description
subcutaneous injection, once a week
Primary Outcome Measure Information:
Title
Change in HbA1c From Baseline to Week 26
Description
Absolute change in HbA1c from baseline (Day 1) to Week 26 [Week 26 - Baseline].
Time Frame
Day 1, Week 26
Secondary Outcome Measure Information:
Title
Percentage of Subjects Achieving HbA1c Target of <7% at Week 26
Description
Percentages of subjects achieving HbA1c target values of <7% at Week 26.
Time Frame
Week 26
Title
Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26
Description
Percentages of subjects achieving HbA1c target values of <=6.5% at Week 26.
Time Frame
Week 26
Title
Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26
Description
Percentages of subjects achieving HbA1c target values of <=6.0% at Week 26.
Time Frame
Week 26
Title
Change in Body Weight From Baseline to Week 26
Description
Change in body weight from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Change in Fasting Plasma Glucose From Baseline to Week 26
Description
Change in fasting plasma glucose from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Change in Systolic Blood Pressure From Baseline to Week 26
Description
Change in systolic blood pressure from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Change in Diastolic Blood Pressure From Baseline to Week 26
Description
Change in diastolic blood pressure from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Change in Fasting Total Cholesterol From Baseline to Week 26
Description
Change in fasting total cholesterol from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26
Description
Change in fasting HDL from baseline (Day 1) to Week 26.
Time Frame
Day 1, Week 26
Title
Ratio of Fasting Triglycerides at Week 26 to Baseline
Description
Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Time Frame
Day 1, Week 26
Title
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
Description
Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration < 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration < 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Time Frame
Day 1 to Week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Porter, MD
Organizational Affiliation
Amylin Pharmaceuticals, LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Peoria
State/Province
Arizona
Country
United States
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Artesia
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California
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United States
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Concord
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California
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United States
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Encino
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California
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United States
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Greenbrae
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California
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United States
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La Mesa
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California
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United States
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Orange
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United States
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Walnut Creek
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California
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United States
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Whittier
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California
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United States
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Colorado Springs
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Colorado
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United States
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Washington
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District of Columbia
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United States
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Coral Gables
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Florida
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United States
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Deland
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Florida
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United States
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Melbourne
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Florida
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United States
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Miami
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Florida
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United States
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New Port Richey
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Florida
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Decatur
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Georgia
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Avon
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Indiana
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United States
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Wichita
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Kansas
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United States
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Paducah
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Kentucky
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United States
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Baton Rouge
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Louisiana
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United States
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New Orleans
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Louisiana
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Oxon Hill
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Maryland
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Boston
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Massachusetts
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United States
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Chelsea
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United States
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Ypsilanti
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United States
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St. Louis Park
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Minnesota
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United States
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St. Louis
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Missouri
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United States
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Butte
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Montana
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United States
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Lincoln
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Nebraska
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United States
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Las Vegas
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Nevada
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United States
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New Hyde Park
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New York
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United States
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New Windsor
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New York
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United States
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New York
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New York
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United States
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Rochester
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New York
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United States
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Durham
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North Carolina
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United States
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Statesville
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North Carolina
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United States
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Winston-Salem
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North Carolina
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United States
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Athens
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Ohio
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United States
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Cincinnati
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Ohio
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United States
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Dayton
State/Province
Ohio
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United States
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Philadelphia
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Pennsylvania
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United States
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Rapid City
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South Dakota
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United States
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Memphis
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Tennessee
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United States
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Austin
State/Province
Texas
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United States
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Dallas
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Texas
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United States
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San Antonio
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Texas
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United States
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Richmond
State/Province
Virginia
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United States
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Olympia
State/Province
Washington
Country
United States
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Spokane
State/Province
Washington
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United States
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Tacoma
State/Province
Washington
Country
United States
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Bangalore
Country
India
Facility Name
Research Site
City
Indore
Country
India
Facility Name
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City
Karnal
Country
India
Facility Name
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Mumbai
Country
India
Facility Name
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City
Pune
Country
India
Facility Name
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City
Mexico City
State/Province
Distrito Federal
Country
Mexico
Facility Name
Research Site
City
Guadalajara
State/Province
Jalisco
Country
Mexico
Facility Name
Research Site
City
Zapopan
State/Province
Jalisco
Country
Mexico
Facility Name
Research Site
City
Cuernavaca
State/Province
Morelos
Country
Mexico
Facility Name
Research Site
City
Monterrey
State/Province
NuevoLeon
Country
Mexico
Facility Name
Research Site
City
Toluca
Country
Mexico
12. IPD Sharing Statement
Citations:
PubMed Identifier
32306296
Citation
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. Erratum In: Diabetes Ther. 2020 Dec;11(12):3011-3013.
Results Reference
derived
PubMed Identifier
23748507
Citation
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.
Results Reference
derived
PubMed Identifier
23748506
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.
Results Reference
derived
PubMed Identifier
23522121
Citation
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.
Results Reference
derived
PubMed Identifier
23039868
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.
Results Reference
derived
PubMed Identifier
22236356
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.
Results Reference
derived
PubMed Identifier
21434995
Citation
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.
Results Reference
derived
PubMed Identifier
20580422
Citation
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.
Results Reference
derived
Learn more about this trial
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)
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