Text Size

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)

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier:
NCT00676338
First received: May 9, 2008
Last updated: February 11, 2013
Last verified: February 2013
History of Changes
  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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
 Drug: exenatide once weekly
Drug: metformin
Drug: sitagliptin
Drug: pioglitazone
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Amylin Pharmaceuticals, LLC.:

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%).


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.


Enrollment: 820
Study Start Date: November 2008
Study Completion Date: January 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide Once Weekly Drug: exenatide once weekly
subcutaneous injection, 2mg, once weekly plus placebo oral once daily
Active Comparator: Metformin Drug: metformin
oral, 1000-2500mg, daily plus placebo once weekly subcutaneous injection
Active Comparator: Sitagliptin Drug: sitagliptin
oral, 100 mg, daily plus placebo once weekly subcutaneous injection
Active Comparator: Pioglitazone Drug: pioglitazone
oral, 30-45mg, daily plus placebo once weekly subcutaneous injection

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00676338

  Show 106 Study Locations
Sponsors and Collaborators
Amylin Pharmaceuticals, LLC.
Eli Lilly and Company
Investigators
Study Director: Chief Medical Officer, MD Eli Lilly and Company
  More Information

No publications provided by Amylin Pharmaceuticals, LLC.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Amylin Pharmaceuticals, LLC.
ClinicalTrials.gov Identifier: NCT00676338     History of Changes
Other Study ID Numbers: H8O-MC-GWCH (DURATION - 4)
Study First Received: May 9, 2008
Results First Received: February 14, 2012
Last Updated: February 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amylin Pharmaceuticals, LLC.:
Amylin
Lilly
exenatide once weekly
Byetta
 Januvia
sitagliptin
thiazolidinedione

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Exenatide
2,4-thiazolidinedione
Sitagliptin
 Metformin
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013