Safety and Efficacy of Exenatide Injection in Subjects With Type 2 Diabetes Mellitus

• Proportion of subjects positive for anti-exenatide antibodies. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• Incidence of potentially immune-related treatment-emergent adverse events will be evaluated. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

• Investigator's global impression of change. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

  Investigator's global impression of change will be recorded at end of trial or premature trial termination visit on a scale of 1-7 as follows:

  Scale: Overall impression

  1. Very much improved
  2. Much improved
  3. Minimally improved
  4. No change
  5. Minimally worse
  6. Much worse
  7. Very much worse
• Shifts in vital signs and other laboratory safety parameters from baseline to end-of-trial. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• Other (non-immune-related) treatment-emergent adverse events will be evaluated. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• Subject's global impression of change [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

  Subject's global impression of change will be recorded at end of trial or premature trial termination visit on a scale of 1-7 as follows:

  Scale: Overall impression

  1. Very much improved
  2. Much improved
  3. Minimally improved
  4. No change
  5. Minimally worse
  6. Much worse
  7. Very much worse

• Investigator's global impression of change and subject's global impression of change. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

  Investigator's global impression of change and subject's global impression of change will be recorded at end of trial or premature trial termination visit on a scale of 1-7 as follows:

  Scale: Overall impression

  1. Very much improved
  2. Much improved
  3. Minimally improved
  4. No change
  5. Minimally worse
  6. Much worse
  7. Very much worse
• Shifts in vital signs and other laboratory safety parameters from baseline to end-of-trial. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
• Other (non-immune-related) treatment-emergent adverse events will be evaluated. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]

Exenatide is the first in a new class of drugs for the treatment of type 2 diabetes mellitus called incretin mimetics. Exenatide resembles a gut hormone, which increases the insulin secretion, thus helps in reducing blood glucose levels. The purpose of study is to establish safety and efficacy of exenatide injection which will be supplied in the form of a reusable pen with cartridge containing exenatide for self administration.

Exenatide subcutaneous injection is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione, but have not achieved adequate glycemic control.

In this randomized, double blind, placebo controlled, parallel groups, multi-centric, 24-week trial, anti-exenatide antibody generation after administration of exenatide injection versus placebo and its impact on efficacy and safety will be evaluated. Subjects will receive exenatide or placebo injection 5 mcg twice daily for the first 4 weeks and 10 mcg twice daily for the remaining 20 weeks. Injection is to be self-administered with a pen injector subcutaneously twice daily in the thigh, abdomen, or upper arm within the 60-minute period before the morning and evening meals (or before the two main meals of the day) at least 6 hours apart.

• Experimental: Exenatide injection
  Intervention: Drug: Exenatide, Placebo
• Placebo Comparator: Placebo
  Intervention: Drug: Exenatide, Placebo

Inclusion Criteria:

• Male and female subjects 20 years of age and older.
• Established clinical diagnosis of type 2 diabetes mellitus treated with diet and exercise or anti-diabetic agents as monotherapy or combination therapy.
• Weight stable: their weight should not have varied more than 10% of screening visit weight, within 6 months prior to screening visit.
• Women of child bearing potential practicing an acceptable method of birth control as judged by the investigator(s); with a negative urine pregnancy test.
• Willing to participate and give written informed consent.

Exclusion Criteria:

• Previous exposure to exenatide (anti-exenatide antibodies at screening) or a GLP-1 analogue.
• Used drugs for weight loss (for example, orlistat, sibutramine, phenylpropanolamine, rimonabant, or similar over-the-counter medications) within 3 months of screening.
• Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of trial entry.
• Severe renal impairment (creatinine clearance <30 ml/min) or end stage renal disease.