Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: exenatide
Intervention description: subcutaneous injection, 2.0mcg, once weekly
Intervention MeSH terms: Exenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Amylin; Lilly; exenatide once weekly; thiazolidinedione; metformin

Summary:

      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.
    

Eligibility 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.