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

NCT00753896 | Completed Phase 3 Results

• 1 other identifier: H8O-MC-GWDC
• Study Type: interventional
• Target: 134
• Locations: 5 countries
• Sites: 26

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.

Conditions

Type 2 Diabetes

Keywords

Amylin; Lilly; exenatide once weekly; thiazolidinedione; metformin

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Change in HbA1c From Baseline to Week 52

  Baseline, Week 52

• Percentage of Patients Achieving HbA1c <=7% at Week 52

  Baseline, Week 52

• Percentage of Patients Achieving HbA1c <=6.5% at Week 52

  Baseline, Week 52

• Change in Fasting Serum Glucose From Baseline to Week 52

  Baseline, Week 52

• Change in Body Weight From Baseline to Week 52

  Baseline, Week 52

Study Arms (1)

1

EXPERIMENTAL

Drug: exenatide

Interventions

exenatide DRUG

subcutaneous injection, 2.0mcg, once weekly

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Eli Lilly and Company: collaborator

Study Sites (26)

Research Site

Mesa, Arizona, United States

Location

Research Site

Tempe, Arizona, United States

Location

Research Site

Concord, California, United States

Location

Research Site

Fresno, California, United States

Location

Research Site

La Mesa, California, United States

Location

Research Site

Atlanta, Georgia, United States

Location

Research Site

Idaho Falls, Idaho, United States

Location

Research Site

Bowling Green, Kentucky, United States

Location

Research Site

Corvallis, Oregon, United States

Location

Research Site

Chattanooga, Tennessee, United States

Location

Research Site

Memphis, Tennessee, United States

Location

Research Site

New Westminster, British Columbia, Canada

Location

Research Site

Ajax, Ontario, Canada

Location

Research Site

Cambridge, Ontario, Canada

Location

Research Site

Windsor, Ontario, Canada

Location

Research Site

Chihuahua City, Chiuahua, Mexico

Location

Research Site

Monterrey, Nuevo León, Mexico

Location

Research Site

Distrito Federal, Mexico

Location

Research Site

Baia Mare, Romania

Location

Research Site

Brasov, Romania

Location

Research Site

Bucharesti, Romania

Location

Research Site

Craiova, Romania

Location

Research Site

Iași, Romania

Location

Research Site

Suceava, Romania

Location

Research Site

Johannesburg, South Africa

Location

Research Site

Pretoria, South Africa

Location

Related Publications (1)

• 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.

  PMID: 23031623 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Peter Ohman, Medical Science Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Chief Medical Officer, MD

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2008
• First Posted: September 17, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: November 1, 2009
• Last Updated: April 21, 2015
• Results First Posted: March 20, 2012

Record last verified: 2015-03

Locations

ZA (2); ME (3); RO (6); CA (4); US (11)