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):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00676338
First received: May 9, 2008
Last updated: June 6, 2014
Last verified: June 2014

May 9, 2008
June 6, 2014
November 2008
July 2010   (final data collection date for primary outcome measure)
  • 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%).
Test hypothesis that exenatide once weekly is superior to metformin, sitagliptin, and pioglitazone in HbA1c reduction at 26 weeks compared to baseline, in drug-naive patients with type 2 diabetes who are inadequately treated with diet and exercise. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00676338 on ClinicalTrials.gov Archive Site
  • 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.
  • Compare exenatide once weekly to metformin, sitagliptin, and pioglitazone with respect to HbA1c, change in fasting serum glucose, change in body weight, self-monitored blood glucose profile, and change in serum lipids. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
  • Compare exenatide once weekly to metformin, sitagliptin, and pioglitazone with respect to incidence of hypoglycemic events, change in blood pressure, safety and tolerability, and health outcomes. [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: 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
  • Experimental: Exenatide Once Weekly
    Intervention: Drug: exenatide once weekly
  • Active Comparator: Metformin
    Intervention: Drug: metformin
  • Active Comparator: Sitagliptin
    Intervention: Drug: sitagliptin
  • Active Comparator: Pioglitazone
    Intervention: Drug: pioglitazone

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
820
January 2011
July 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United 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
 
NCT00676338
H8O-MC-GWCH (DURATION - 4)
No
AstraZeneca
AstraZeneca
Eli Lilly and Company
Study Director: Chief Medical Officer, MD Eli Lilly and Company
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP