Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00753896
First received: September 15, 2008
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This study will examine the safety of exenatide once weekly (2.0 mg) in approximately 134 patients receiving treatment with thiazolidinedione alone or thiazolidinedione in combination with metformin. Patients are expected to be treated with exenatide once weekly for at least 52 weeks.


Condition Intervention Phase
Type 2 Diabetes
Drug: exenatide
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Percentage of Patients Experiencing Adverse Events [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: Yes ]
    Percentage of patients experiencing treatment-emergent adverse events over 52 weeks

  • Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events [ Time Frame: Baseline to Week 52 ] [ 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 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).


Secondary Outcome Measures:
  • Change in HbA1c From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in HbA1c from baseline to endpoint

  • Percentage of Patients Achieving HbA1c <=7% at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Percentage of patients achieving HbA1c <=7% at endpoint (for patients with HbA1c >7% at baseline)

  • Percentage of Patients Achieving HbA1c <=6.5% at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Percentage of patients achieving HbA1c <=6.5% at endpoint (for patients with HbA1c >6.5% at baseline)

  • Change in Fasting Serum Glucose From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in fasting serum glucose from baseline to endpoint

  • Change in Body Weight From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in body weight from baseline to endpoint

  • Change in Total Cholesterol From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in Total Cholesterol from baseline to endpoint

  • Change in High-density Lipoprotein (HDL) From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in HDL from baseline to endpoint

  • Change in Triglycerides From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in Triglycerides from baseline to endpoint

  • Change in Blood Pressure From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
    Change in Systolic and Diastolic Blood Pressure from baseline to endpoint


Enrollment: 134
Study Start Date: October 2008
Study Completion Date: November 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: exenatide
subcutaneous injection, 2.0mcg, once weekly

  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
  • At least 18 years of age at screening.
  • Have HbA1c of 7.1% to 10.0%, inclusive, at screening.
  • Have a body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive.
  • Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days prior to Visit 1 OR Have been treated with a stable dose of TZD (≥4 mg/day rosiglitazone or ≥30 mg/day pioglitazone) for at least 120 days PLUS a stable dose of metformin for at least 90 days prior to Visit 1.
  • Have a history of stable body weight (not varying by >10% for at least 3 months prior to screening).
  • If female of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopause) only.

    • Are not breastfeeding.
    • Test negative for pregnancy at the time of screening based on a serum pregnancy test.
    • Intend not to become pregnant during the study.
    • Have practiced a reliable method of birth control (e.g., use of oral contraceptives or approved hormonal implant; diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) for at least 6 weeks prior to screening.
    • Agree to continue to use a reliable method of birth control (see above) during the study.

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, coronary artery bypass surgery, angioplasty.
  • Is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
  • Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis
  • Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine ≥135 μmol/L for males and ≥110 μmol/L for females.
  • 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 known hemoglobinopathy or chronic anemia (hemoglobin concentration <11.5 g/dL [115 g/L] for males, <10.5 g/dL [105 g/L] for females).
  • Have clinically significant history or presence of severe gastrointestinal disease, particularly those which may impact gastric emptying, such as gastroparesis, pyloric stenosis, or gastric bypass surgery.
  • Have a history of pancreatitis.
  • Have had greater than three episodes of major hypoglycemia within 6 months prior to screening.
  • Have any contraindication for the OAD(s) which they use, according to local label requirements.
  • Are known to have active proliferative retinopathy.
  • Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical or inhaled preparations) or have received systemic glucocorticoid therapy for >2 weeks within the 4 weeks immediately preceding screening.
  • 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 previously been treated with glucagon-like peptide 1 analogs or liraglutide.
  • Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening: Insulin; Sulfonylureas; Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose]); Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]); 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 participating in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment is given). Patients completing the final visit of a study examining safety/efficacy of exenatide BID may enter this study on the same day if they meet other eligibility criteria.
  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: NCT00753896

Locations
United States, Arizona
Research Site
Mesa, Arizona, United States
Research Site
Tempe, Arizona, United States
United States, California
Research Site
Concord, California, United States
Research Site
Fresno, California, United States
Research Site
La Mesa, California, United States
United States, Georgia
Research Site
Atlanta, Georgia, United States
United States, Idaho
Research Site
Idaho Falls, Idaho, United States
United States, Kentucky
Research Site
Bowling Green, Kentucky, United States
United States, Oregon
Research Site
Corvallis, Oregon, United States
United States, Tennessee
Research Site
Chattanooga, Tennessee, United States
Research Site
Memphis, Tennessee, United States
Canada, British Columbia
Research Site
New Westminister, British Columbia, Canada
Canada, Ontario
Research Site
Ajax, Ontario, Canada
Research Site
Cambridge, Ontario, Canada
Research Site
Windsor, Ontario, Canada
Mexico
Research Site
Chihuahua, Chiuahua, Mexico
Research Site
Monterrey, Nuevo Leon, Mexico
Research Site
Distrito Federal, Mexico
Romania
Research Site
Baia Mare, Romania
Research Site
Brasov, Romania
Research Site
Bucharesti, Romania
Research Site
Craiova, Romania
Research Site
Iasi, Romania
Research Site
Suceava, Romania
South Africa
Research Site
Johannesburg, South Africa
Research Site
Pretoria, South Africa
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: NCT00753896     History of Changes
Other Study ID Numbers: H8O-MC-GWDC
Study First Received: September 15, 2008
Results First Received: February 14, 2012
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Amylin
Lilly
exenatide once weekly
thiazolidinedione
metformin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Exenatide
2,4-thiazolidinedione
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014