Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3)

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00641056
First received: March 17, 2008
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to compare the effects of 2.0 mg exenatide once weekly and insulin glargine, titrated to glucose targets using the algorithm described by Yki- Järvinen et al.(2007), with respect to glycemic improvements, body weight, fasting lipids, safety, and tolerability.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Exenatide Once Weekly
Drug: Insulin Glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy of Once-Weekly Exenatide Long-Acting Release and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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


Secondary Outcome Measures:
  • Percentage of Patients Achieving HbA1c <=7.0% at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Percentage of patients achieving HbA1c <=7.0% at Week 26 (for patients with HbA1c >7% at baseline)

  • Percentage of Patients Achieving HbA1c <=6.5% at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Percentage of patients achieving HbA1c <=6.5% at Week 26 (for patients with HbA1c >6.5% at baseline)

  • Change in Fasting Serum Glucose (FSG) From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Change in FSG (mmol/L) from Baseline to Week 26

  • Change in Body Weight (BW) From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Change in BW (kg) from Baseline to Week 26

  • Change in Total Cholesterol From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Change in Total Cholesterol (mmol/L) from Baseline to Week 26

  • Change in High-density Lipoprotein Cholesterol (HDL) From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Change in HDL (mmol/L) from Baseline to Week 26

  • Ratio of Triglycerides at Week 26 to Baseline [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Ratio of Triglycerides (measured in mmol/L) at Week 26 to Baseline. Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.

  • Change in Blood Pressure From Baseline to Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    Change in Systolic Blood Pressure (mmHg) and Diastolic Blood Pressure (mmHg) from Baseline to Week 26

  • Assessment on Event Rate of Treatment-emergent Hypoglycemic Episodes [ Time Frame: Baseline to Week 26 ] [ Designated as safety issue: Yes ]
    Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose or documented hypoglycemia (blood glucose <3.0 mmol/L [54 mg/dL]) and required the assistance of another person. Minor hypoglycemia: any time a patient felt that he or she was experiencing a sign or symptom of hypoglycemia that was self-treated or resolved on its own and had a blood glucose level <3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia.


Enrollment: 467
Study Start Date: April 2008
Study Completion Date: November 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Exenatide Once Weekly
subcutaneous injection, 2.0mcg, once weekly
Active Comparator: 2 Drug: Insulin Glargine
subcutaneous injection, variable dose, QD

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has type 2 diabetes and at least 18 years of age at screening.
  • Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
  • Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.
  • Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).
  • Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening OR
  • Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening and have been treated with SU for at least 3 months and have been taking a stable dose of at least an optimally effective dose of brand of SU for 8 weeks prior to screening.

Exclusion Criteria:

  • Have had a clinically significant 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; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
  • Have clinical signs or symptoms of liver disease, acute or chronic hepatitis.
  • 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 had greater than three episodes of major hypoglycemia within 6 months prior to screening.
  • Have any contraindication for the oral antidiabetic agent which they use.
  • Have a known allergy or hypersensitivity to insulin glargine, exenatide once weekly, or excipients contained in these agents.
  • Are known to 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 for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening:

    • Insulin
    • Thiazolidinediones (e.g., Actos® [pioglitazone] or Avandia® [rosiglitazone])
    • Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose])
    • Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]).
    • Byetta® (exenatide BID formulation)
    • Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin])
    • Symlin® (pramlintide acetate).
  • Have had an organ transplant.
  • Have donated blood within 30 days of screening.
  • Have previously completed or 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00641056

  Hide Study Locations
Locations
United States, California
Research Site
Escondido, California, United States
United States, Florida
Research Site
Jacksonville, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
West Palm Beach, Florida, United States
United States, Hawaii
Research Site
Honolulu, Hawaii, United States
United States, Idaho
Research Site
Idaho Falls, Idaho, United States
United States, Minnesota
Research Site
Minneapolis, Minnesota, United States
United States, Missouri
Research Site
St. Louis, Missouri, United States
United States, Ohio
Research Site
Dayton, Ohio, United States
United States, Oklahoma
Research Site
Ada, Oklahoma, United States
United States, Texas
Research Site
San Antonio, Texas, United States
United States, Washington
Research Site
Spokane, Washington, United States
Australia, New South Wales
Research Site
Wollongong, New South Wales, Australia
Australia, Queensland
Research Site
Herston, Queensland, Australia
Australia, South Australia
Research Site
Adelaide, South Australia, Australia
Research Site
Keswick, South Australia, Australia
Australia, Victoria
Research Site
Box Hill, Victoria, Australia
Research Site
Geelong, Victoria, Australia
Belgium
Research Site
Brussels, Belgium
Research Site
Edegem, Belgium
Czech Republic
Research Site
Melnik, Czech Republic
Research Site
Praha, Czech Republic
Research Site
Stodulky, Czech Republic
Denmark
Research Site
Aalborg, Denmark
Research Site
Arhus C, Denmark
Research Site
Herlev, Denmark
Research Site
Koge, Denmark
France
Research Site
Angers, France
Research Site
Corbeil Essoness, France
Research Site
Nancy, France
Research Site
Nanterre, France
Research Site
Toulouse, France
Germany
Research Site
Bad Mergentheim, Germany
Research Site
Dresden, Germany
Research Site
Essen, Germany
Research Site
Falkensee, Germany
Research Site
Fulda, Germany
Research Site
Hamburg-Othmarschen, Germany
Research Site
Munster, Germany
Research Site
Rothenburg an der fulda, Germany
Research Site
Speyer, Germany
Greece
Research Site
Athens, Greece
Research Site
Thessaloniki, Greece
Hungary
Research Site
Budapest, Hungary
Research Site
Eger, Hungary
Research Site
Gyula, Hungary
Research Site
Pecs, Hungary
Korea, Republic of
Research Site
Gyeonggi-Do, Korea, Republic of
Research Site
Seoul, Korea, Republic of
Mexico
Research Site
Merida, Mexico
Research Site
Mexico City, Mexico
Research Site
Tampico, Mexico
Research Site
Tijuana, Mexico
Netherlands
Research Site
Amsterdam, Netherlands
Research Site
Gouda, Netherlands
Research Site
Hoogeveen, Netherlands
Research Site
Rotterdam, Netherlands
Research Site
Zwijndrecht, Netherlands
Research Site
Zwolle, Netherlands
Puerto Rico
Research Site
Caguas, Puerto Rico
Research Site
Yabucoa, Puerto Rico
Russian Federation
Research Site
Moscow, Russian Federation
Research Site
Rostov-on-Don, Russian Federation
Research Site
St. Petersburg, Russian Federation
Spain
Research Site
Alicante, Spain
Research Site
Alzira-Valencia, Spain
Research Site
Barcelona, Spain
Research Site
Bilbao, Spain
Research Site
Madrid, Spain
Research Site
Malaga, Spain
Research Site
Teruel, Spain
Taiwan
Research Site
Chia-Yi, Taiwan
Research Site
Tainan County, Taiwan
Research Site
Taipei, Taiwan
Research Site
Taoyuan, Taiwan
Sponsors and Collaborators
AstraZeneca
Eli Lilly and Company
Investigators
Study Director: Chief Medical Officer, MD Eli Lilly and Company
  More Information

No publications provided by AstraZeneca

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

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00641056     History of Changes
Other Study ID Numbers: H8O-MC-GWBR (DURATION - 3)
Study First Received: March 17, 2008
Results First Received: February 14, 2012
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
diabetes
exenatide
exenatide once weekly
metformin
sulfonylurea
insulin glargine
Amylin
Lilly

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Glargine
Exenatide
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 01, 2014