Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)

Overview[ - collapse ][ - ]

Purpose This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione) in drug naive patients with type 2 diabetes treated with diet and exercise.
ConditionType 2 Diabetes Mellitus
InterventionDrug: exenatide once weekly
Drug: metformin
Drug: sitagliptin
Drug: pioglitazone
PhasePhase 3
SponsorBristol-Myers Squibb
Responsible PartyBristol-Myers Squibb
ClinicalTrials.gov IdentifierNCT00676338
First ReceivedMay 9, 2008
Last UpdatedSeptember 17, 2013
Last verifiedSeptember 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 9, 2008
Last Updated DateSeptember 17, 2013
Start DateNovember 2008
Estimated Primary Completion DateJanuary 2011
Current Primary Outcome Measures
  • Change in HbA1c From Baseline to Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Change in HbA1c from baseline to Week 26.
  • Percentage of Patients Achieving HbA1c <=7% at Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Percentage of patients achieving HbA1c <=7% at Week 26 (for patients with baseline HbA1c >7%).
Current Secondary Outcome Measures
  • Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Change in FSG from baseline to Week 26.
  • Change in Body Weight From Baseline to Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Change in Body Weight from baseline to Week 26.
  • Change in Fasting Total Cholesterol (TC) From Baseline to Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Change in Fasting TC from baseline to Week 26.
  • Change in Fasting High-Density Lipoprotein (HDL) From Baseline to Week 26 [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Change in Fasting HDL from baseline to Week 26.
  • Ratio of Fasting Triglycerides at Week 26 to Baseline [Time Frame: Baseline, Week 26] [Designated as safety issue: No]Ratio of Fasting Triglycerides (measured in mmol/L) at Week 26 to baseline. Log(Post-baseline Triglycerides) - log(Baseline Triglycerides); change from baseline to Week 26 is presented as ratio of endpoint to baseline.
  • Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events [Time Frame: Baseline to Week 26] [Designated as safety issue: Yes]Major hypoglycemia is defined as any event that has symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure that shows prompt recovery in response to administration of glucagon or glucose, or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) requiring the assistance of another person because of severe impairment in consciousness or behavior (whether or not symptoms of hypoglycemia are detected by the patient). Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).
  • Assessment on Event Rate of Treatment-Emergent Minor Hypoglycemic Events [Time Frame: Baseline to Week 26] [Designated as safety issue: Yes]Minor hypoglycemia is defined as a sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)**2).
  • Change in Systolic Blood Pressure From Baseline to Week 26. [Time Frame: Baseline, Week 26] [Designated as safety issue: Yes]Change in Systolic Blood Pressure from baseline to Week 26.
  • Change in Diastolic Blood Pressure From Baseline to Week 26. [Time Frame: Baseline, Week 26] [Designated as safety issue: Yes]Change in Diastolic Blood Pressure from baseline to Week 26.

Descriptive Information[ + expand ][ + ]

Brief TitleSafety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes (DURATION-4)
Official TitleSafety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes
Brief Summary
This study will compare the effects of 2.0 mg exenatide once weekly injection as monotherapy
to 3 active comparators(metformin, dipeptidyl peptidase-4 inhibitor, and thiazolidinedione)
in drug naive patients with type 2 diabetes treated with diet and exercise.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionType 2 Diabetes Mellitus
InterventionDrug: exenatide once weekly
subcutaneous injection, 2mg, once weekly plus placebo oral once daily
Drug: metformin
oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection
Drug: sitagliptin
oral, 100 mg, daily plus placebo once weekly subcutaneous injection
Drug: pioglitazone
oral, 30-45mg, daily plus placebo once weekly subcutaneous injection
Study Arm (s)
  • Experimental: Exenatide Once Weekly
  • Active Comparator: Metformin
  • Active Comparator: Sitagliptin
  • Active Comparator: Pioglitazone

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment820
Estimated Completion DateJanuary 2011
Estimated Primary Completion DateJuly 2010
Eligibility Criteria
Inclusion Criteria:

- have type 2 diabetes and are treated with diet and exercise alone.

- at least 18 years of age.

- HbA1c between 7.1% and 11.0%, inclusive.

- Body mass index (BMI) of 23 kg/m2 to 45 kg/m2, inclusive.

- Have a history of stable body weight (not varying by >5% for at least 3 months prior
to screening).

Exclusion Criteria:

- Have history of cardiac disease or presence of active cardiac disease within the year
prior to inclusion in the study including myocardial infarction, clinically
significant arrhythmia, unstable angina, moderate to severe congestive heart failure,
coronary artery bypass surgery, or angioplasty

- Have a history of renal transplantation or are currently receiving renal dialysis

- Have active or untreated malignancy, or have been in remission from clinically
significant malignancy (other than basal cell or squamous cell skin cancer, in situ
carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.

- Have history of severe GI disorder (e.g., gastroparesis)

- Have a history of acute or chronic pancreatitis.

- Have active proliferative retinopathy.

- Have been treated with drugs that promote weight loss (e.g., Xenical®[orlistat],
Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or
similar over-the-counter medications) within 3 months of screening.

- Have been treated with any antidiabetic agent for more than 7 days within 3 months
prior to screening.

- Have had an organ transplant.

- Have previously completed or discontinued study drug in this study, withdrawn from
this study or any other study investigating exenatide once weekly.

- Have received treatment within the last 30 days with a drug that has not received
regulatory approval for any indication at the time of study entry.

- Are currently enrolled in any other clinical study.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Belgium, Brazil, Canada, France, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Mexico, Poland, Puerto Rico, Romania, Russian Federation, Slovakia, South Africa, Spain, Turkey, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00676338
Other Study ID NumbersH8O-MC-GWCH (DURATION - 4)
Has Data Monitoring CommitteeNo
Information Provided ByBristol-Myers Squibb
Study SponsorBristol-Myers Squibb
CollaboratorsEli Lilly and Company
Investigators Study Director: Chief Medical Officer, MD Eli Lilly and Company
Verification DateSeptember 2013

Locations[ + expand ][ + ]

Research Site
Buena Park, California, United States
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Los Angeles, California, United States
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Valencia, California, United States
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Jacksonville, Florida, United States
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Atlanta, Georgia, United States
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Meridian, Idaho, United States
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Des Moines, Iowa, United States
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Grand Rapids, Michigan, United States
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Minneapolis, Minnesota, United States
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Billings, Montana, United States
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Toms River, New Jersey, United States
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Wilmington, North Carolina, United States
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Danville, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Wilke Barre, Pennsylvania, United States
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Austin, Texas, United States
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El Paso, Texas, United States
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New Branufels, Texas, United States
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Buenos Aires, Argentina
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Mar del Plata, Argentina
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Leuven, Belgium
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Marchovelette, Belgium
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Tessenderlo, Belgium
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Brasilia, Brazil
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Campinas, Brazil
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Curitiba, Brazil
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Fortaleza, Brazil
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Joinville, Brazil
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Porto Alegre, Brazil
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Recife, Brazil
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Sao Paolo, Brazil
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Coquitlam, British Columbia, Canada
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Penticton, British Columbia, Canada
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Ottawa, Ontario, Canada
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Gatineu, Quebec, Canada
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Mississauga, Canada
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Petitcodiac, Canada
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Pointe-Claire, Canada
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Regina, Canada
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Saint John, Canada
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Chateaugiron, France
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Murs Erigne, France
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Nantes, France
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Vieux Conde, France
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Dresden, Germany
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Mainz, Germany
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Muenster, Germany
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Rodgau, Germany
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Budapest, Hungary
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Gyula, Hungary
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Hodmezovasarhely, Hungary
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Pecs, Hungary
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Ahmedabad, India
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Bangalore, India
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Channai, India
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Cochin, India
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Mumbai, India
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New Dehli, India
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Pune, India
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Holon, Israel
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Tel-Hashomer, Israel
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Firenze, Italy
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Milano, Italy
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Siena, Italy
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Busan, Korea, Republic of
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Daegu, Korea, Republic of
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Jeonju, Korea, Republic of
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Seoul, Korea, Republic of
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Sungnam, Korea, Republic of
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Chihuahua, Mexico
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Guadalajara, Mexico
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Monterrey, Mexico
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Lublin, Poland
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Szczecin, Poland
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Wroclaw, Poland
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Manati, Puerto Rico
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Toa Baja, Puerto Rico
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Galati, Romania
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Oradea, Romania
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Targu Mures, Romania
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Arkhangelsk, Russian Federation
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Moscow, Russian Federation
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Rostov-on-Don, Russian Federation
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Saint Petersburg, Russian Federation
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Stavropol, Russian Federation
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Bratislava, Slovakia
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Trebisov, Slovakia
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Johannesburg, South Africa
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Kempton Park, South Africa
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Midrand, South Africa
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Soweto, South Africa
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Alicante, Spain
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Barcelona, Spain
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Madrid, Spain
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Sevilla, Spain
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Ankara, Turkey
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Istanbul, Turkey
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Sisli-Istanbul, Turkey
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Bath, United Kingdom
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Birmingham, United Kingdom
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Edinburgh, United Kingdom
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Frome, United Kingdom
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Guildford, United Kingdom
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Hull, United Kingdom
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Sheffield, United Kingdom
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Swansea, United Kingdom