| Abstract: | Objective: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low‐calorie diet. Research Methods and Procedures: Obese subjects (30 ≤ BMI < 50 kg/m2) 18 to 75 years old received a low‐calorie diet for 8 weeks. Those who lost ≥8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled‐release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. Results: Of the 701 subjects enrolled, 80% lost ≥8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run‐in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. Discussion: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low‐calorie diet—and produced additional clinically significant weight loss beyond that achieved by a low‐calorie diet. |
