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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: exenatide

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • New Westminister, British Columbia, Canada
      • Research Site
  • Ontario
    • Ajax, Ontario, Canada
      • Research Site
    • Cambridge, Ontario, Canada
      • Research Site
    • Windsor, Ontario, Canada
      • Research Site
• Mexico
  • Distrito Federal, Mexico
    • Research Site
  • Chiuahua
    • Chihuahua, Chiuahua, Mexico
      • Research Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico
      • Research Site
• Romania
  • Baia Mare, Romania
    • Research Site
  • Brasov, Romania
    • Research Site
  • Bucharesti, Romania
    • Research Site
  • Craiova, Romania
    • Research Site
  • Iasi, Romania
    • Research Site
  • Suceava, Romania
    • Research Site
• South Africa
  • Johannesburg, South Africa
    • Research Site
  • Pretoria, South Africa
    • Research Site
• United States
  • Arizona
    • Mesa, Arizona, United States
      • Research Site
    • Tempe, Arizona, United States
      • Research Site
  • California
    • Concord, California, United States
      • Research Site
    • Fresno, California, United States
      • Research Site
    • La Mesa, California, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Idaho
    • Idaho Falls, Idaho, United States
      • Research Site
  • Kentucky
    • Bowling Green, Kentucky, United States
      • Research Site
  • Oregon
    • Corvallis, Oregon, United States
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States
      • Research Site
    • Memphis, Tennessee, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: exenatide; subcutaneous injection, 2.0mcg, once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Experiencing Adverse Events	Percentage of patients experiencing treatment-emergent adverse events over 52 weeks	Baseline to Week 52
Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events	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).	Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c From Baseline to Week 52	Change in HbA1c from baseline to endpoint	Baseline, Week 52
Percentage of Patients Achieving HbA1c <=7% at Week 52	Percentage of patients achieving HbA1c <=7% at endpoint (for patients with HbA1c >7% at baseline)	Baseline, Week 52
Percentage of Patients Achieving HbA1c <=6.5% at Week 52	Percentage of patients achieving HbA1c <=6.5% at endpoint (for patients with HbA1c >6.5% at baseline)	Baseline, Week 52
Change in Fasting Serum Glucose From Baseline to Week 52	Change in fasting serum glucose from baseline to endpoint	Baseline, Week 52
Change in Body Weight From Baseline to Week 52	Change in body weight from baseline to endpoint	Baseline, Week 52
Change in Total Cholesterol From Baseline to Week 52	Change in Total Cholesterol from baseline to endpoint	Baseline, Week 52
Change in High-density Lipoprotein (HDL) From Baseline to Week 52	Change in HDL from baseline to endpoint	Baseline, Week 52
Change in Triglycerides From Baseline to Week 52	Change in Triglycerides from baseline to endpoint	Baseline, Week 52
Change in Blood Pressure From Baseline to Week 52	Change in Systolic and Diastolic Blood Pressure from baseline to endpoint	Baseline, Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Norwood P, Liutkus JF, Haber H, Pintilei E, Boardman MK, Trautmann ME. Safety of exenatide once weekly in patients with type 2 diabetes mellitus treated with a thiazolidinedione alone or in combination with metformin for 2 years. Clin Ther. 2012 Oct;34(10):2082-90. doi: 10.1016/j.clinthera.2012.09.007. Epub 2012 Sep 29.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: September 15, 2008
• First Submitted That Met QC Criteria: September 15, 2008
• First Posted (Estimate): September 17, 2008

Study Record Updates

• Last Update Posted (Estimate): April 21, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: metformin; thiazolidinedione; Lilly; Amylin; exenatide once weekly
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: H8O-MC-GWDC