A Study of Safety and Efficacy of Topiramate in Male Patients With Abdominal Obesity

The Safety and Efficacy of Topiramate in Male Patients With Abdominal Obesity: A 6-Month Double-Blind, Randomized, Placebo-Controlled Study With a 6-Month Open-Label Extension

The purposes of this study are to compare the effects of Topiramate and placebo on abdominal visceral fat accumulation at 6 months and to evaluate the safety of Topiramate for up to 12 months of continued treatment in male patients with abdominal obesity.

Topiramate is not approved for the treatment of obesity. This study is a 6-month randomized, double-blind placebo-controlled study, followed by a 6-month open-label extension study to evaluate the effect of Topiramate on abdominal visceral fat accumulation, a clinical surrogate known to be associated with the complications of obesity such as increased incidence of Type 2 diabetes mellitus, hypertension, and dyslipidemia, and their associated morbidities. Patients will be randomized to receive either daily Topiramate or placebo. Effectiveness will be measured by multiple parameters such as abdominal visceral fat (assessed by computed tomography), total and subcutaneous abdominal fat, body composition, body weight, body mass index, glucose tolerance, lipid profile, blood pressure, Topiramate plasma concentration, or 24 hours energy expenditure (selected patients). Safety evaluation (adverse events, vital signs, 12-lead ECG, clinical laboratory tests) will be conducted throughout the study. The study hypothesis is that Topiramate is effective in reducing abdominal visceral fat in male patients and well tolerated. After the initial 12-week titration phase, patients will receive either Topiramate (200mg twice daily or the maximum dose tolerated) or placebo by mouth for 6-months. Then, patients will receive Topiramate (200mg twice daily or the maximum tolerated dose) for 6-months during the open-label phase.

Obesity, Abdominal Obesity, Visceral Fat, Subcutaneous Fat, Dislipidemia, Hypertension, Type 2 Diabetes Mellitus

The mean change from baseline to Month 6 in abdominal visceral fat as assessed by computed tomography; the safety of Topiramate for up to 12 months of continued treatment in male subjects with abdominal obesity.

Mean change and percent change in body weight, and mean change in total abdominal fat, subcutaneous abdominal fat, body composition, and body mass index from baseline to Month 6.

Inclusion Criteria: BMI >= 27 and =< 40 a waist circumference >= 100 cm (39.4 inches) Baseline weight must be stable (varying no more than 4 kg (8.8 lbs)) for at least two months prior to enrollment Must be sedentary (less than one session of continuous moderate physical activity of 30 min/week) Must have blood lipid disorder Must be non-smokers Exclusion Criteria: Patients with endocrine disease or other physical causes of obesity Patients with significantly abnormal hepatic liver function tests or renal disease History of schizophrenia, psychotic, or major affective disorder History of epilepsy History of eating disorders History of any other significant medical conditions

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