Evaluation of the Effect on Glucose Control of AC2993 in Patients With Type 2 Diabetes Mellitus Treated With a Sulfonylurea

• Change in HbA1c from baseline (Day 1) to each of the intermediate visits [ Time Frame: Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24 ] [ Designated as safety issue: No ]
  Change in HbA1c from baseline, measured from Visit 3 (Day 1) to each of the intermediate visits (Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, and Week 24
• The number of subjects achieving HbA1c target values of < 7% and < 8% by Week 30 [ Time Frame: Baseline (Day 1) and Week 30 ] [ Designated as safety issue: No ]
  The number of subjects achieving HbA1c target values of < 7% and < 8% by study termination (Week 30)
• The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by Week 30 [ Time Frame: Baseline (Day 1), and Week 30 ] [ Designated as safety issue: No ]
  The number of subjects achieving HbA1c reductions of > 0.5% and > 1.0% by study termination (Week 30)
• The time to achieve HbA1c reductions of 0.5% or more and >1.0% or more [ Time Frame: Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24, Week 30 ] [ Designated as safety issue: No ]
  The time it takes subjects to achieve HbA1c reductions of 0.5% or more and >1.0% or more
• The time to achieve specific HbA1c target values of < 7% and < 8% [ Time Frame: Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24, Week 30 ] [ Designated as safety issue: No ]
  The time it takes subjects to achieve HbA1c target values of < 7% and < 8%
• Change in body weight from Baseline to each intermediate visit and Week 30 [ Time Frame: Baseline (Day 1), Week 2, Week 4, Week 6, Week 12, Week 18, Week 24, Week 30 ] [ Designated as safety issue: No ]
  Change in body weight (kg) from Baseline to each intermediate visit and Week 30

This is a multicenter, randomized, blinded, placebo-controlled study to assess the effects on glucose control of AC2993 as compared to placebo in patients with type 2 diabetes. Patients will be randomized into one of two AC2993 treatment arms or to placebo treatment and will continue with their required existing diabetes medication (sulfonylurea) throughout the study.

• Drug: AC2993
  Placebo Lead In (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 4 weeks / AC2993 5mcg (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily
  Other Name: synthetic exendin-4
• Drug: Placebo
  Placebo Lead In (0.02 mL) for 4 weeks / Placebo (0.02 mL) for 4 weeks / Placebo (0.02 mL) for 26 weeks - All are subcutaneously injected twice daily
• Drug: Placebo
  Placebo Lead In (0.02 mL) for 4 weeks / Placebo mcg (0.02 mL) for 4 weeks / Placebo (0.04 mL) for 26 weeks - All are subcutaneously injected twice daily

• Experimental: AC2993 5 mcg (0.02 mL)
  Placebo, then AC2993 5 mcg, then AC2993 5 mcg
  Intervention: Drug: AC2993
• Experimental: AC2993 10mcg (0.04 mL)
  Placebo, then AC2993 5 mcg, then AC2993 10 mcg
  Intervention: Drug: AC2993
• Placebo Comparator: Placebo 0.02 mL
  Placebo 0.02 mL, then Placebo 0.02 mL, then Placebo 0.02 mL
  Intervention: Drug: Placebo
• Placebo Comparator: Placebo 0.04 mL
  Placebo 0.02 mL / Placebo 0.02 mL / Placebo 0.04 mL
  Intervention: Drug: Placebo

• Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
• Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.

Inclusion Criteria:

• Subjects with Type 2 diabetes mellitus
• Treated with a sulfonylurea at defined doses for at least 3 months prior to screening
• BMI= 27-45 kg/m2
• HbA1c value between 7.5% and 11%

Exclusion Criteria:

• Treated with oral anti-diabetic medications other than a sulfonylurea within 3 months of screening
• Patients treated previously with AC2993
• Patients presently treated with insulin