Clinical trial NCT00753896: Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin
Official title: Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes
Keywords: Amylin
Lilly
exenatide once weekly
thiazolidinedione
metformin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2008-09-17
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percentage of Patients Experiencing Adverse Events
timeFrame: Baseline to Week 52
measure: Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Change in HbA1c From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Patients Achieving HbA1c <=7% at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Patients Achieving HbA1c <=6.5% at Week 52
timeFrame: Baseline, Week 52
measure: Change in Fasting Serum Glucose From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Change in Body Weight From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Change in Total Cholesterol From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Change in High-density Lipoprotein (HDL) From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Change in Triglycerides From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Change in Blood Pressure From Baseline to Week 52
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Research Site
state: Arizona
city: Tempe
country: United States
facility: Research Site
state: Arizona
city: Concord
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Bowling Green
country: United States
facility: Research Site
state: Kentucky
city: Corvallis
country: United States
facility: Research Site
state: Oregon
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: New Westminister
country: Canada
facility: Research Site
state: British Columbia
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Cambridge
country: Canada
facility: Research Site
state: Ontario
city: Windsor
country: Canada
facility: Research Site
state: Ontario
city: Chihuahua
country: Mexico
facility: Research Site
state: Chiuahua
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo Leon
city: Distrito Federal
country: Mexico
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Brasov
country: Romania
facility: Research Site
city: Bucharesti
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Johannesburg
country: South Africa
facility: Research Site
city: Pretoria
country: South Africa
facility: Research Site
Study officials:
affiliation: Eli Lilly and Company
name: Chief Medical Officer, MD
role: STUDY_DIRECTOR
References:
citation: 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.