A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Study to Assess the Efficacy and Safety of Topiramate OROS Controlled-Release in the Treatment of Obese, Type 2 Diabetic Subjects Managed With Diet or Metformin

Topiramate is not approved for the treatment of obesity. Studies have shown that an immediate release formulation of topiramate reduces body weight in obese patients with or without type 2 diabetes. A novel controlled-release formulation of topiramate using OROS® technology has the potential for better efficacy and safety in the treatment of obesity. This double-blind, placebo controlled study will evaluate the effectiveness and safety of the controlled-release formulation in the treatment of obese subjects with type 2 diabetes. The study consists of 2 screening visits, a baseline visit, 7-week titration phase (topiramate dose will be increased from 25mg daily to 175mg daily), 9-week maintenance phase, 2-week taper phase and a 2-week follow-up. Effectiveness will be evaluated by the percent change in body weight, body mass index, and anthropometric measurements (waist and hip circumferences and their ratio). Safety evaluations (incidence and severity of adverse events, physical measurements and clinical laboratory tests) will be conducted throughout the study. The study hypothesis is that topiramate 175 mg daily, when administered as the OROS® controlled-release formulation, is effective (in terms of percent reduction in body weight from baseline to week 16) and safe, as compared with placebo, in the treatment of obese, type 2 diabetic patients managed with either diet alone or combined with metformin. During the titration phase, topiramate (in the OROS® controlled-release formulation) will be gradually increased to 175mg daily by mouth, and the dose will be maintained for 9 weeks, and then slowly discontinued over 2 weeks.