A Study on Efficacy and Safety of Topiramate in Maintaining Weight Loss in Obese Patients Following an Intensive, Non-Pharmacologic Weight Loss Program

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Efficacy and Safety of Topiramate in Weight Loss Maintenance in Obese Patients Following Participation in an Intensive, Non-Pharmacologic Weight Loss Program

The purpose of this study is to compare the efficacy and safety of topiramate 96mg and 192mg daily) with placebo in the treatment of obesity following an intensive non-pharmacologic weight loss program.

Although dietary modification coupled with increased exercise is the preferred treatment of obesity, these lifestyle changes alone are often insufficient in achieving and maintaining weight reduction in obese patients. Topiramate is not approved for the treatment of obesity. This double-blind, placebo controlled study will evaluate the effectiveness and safety of topiramate in maintaining weight loss achieved by an intensive non-drug weight reduction program. Enrolled patients will undergo run-in phase (8 weeks of intensive non-drug weight reduction therapy consisting of a low calorie diet, a behavioral modification program, and an exercise program). Those patients who achieve weight loss of >= 8% of enrollment body weight and meeting the eligibility criteria will be randomized to either 96mg or 192mg of topiramate, or placebo. After 8 weeks of dose titration, the patients will receive one year of treatment. Effectiveness will be assessed by body weight, Body Mass Index (BMI), number and proportion of 5%, 10% and 15% weight loss responders, number and proportion of patients who maintain 50%, 75%, and 100% of weight lost during run-in phase, waist and hip circumferences, fasting lipid profile, fasting plasma glucose, HbA1c, fasting insulin, two-hour glucose tolerance test, uric acid level, blood pressure, body composition, echocardiography, and Health Related Quality of Life scores. Safety evaluations (incidence of adverse events, electrocardiograms, vital signs, etc) will be performed throughout the study. The study hypothesis is that topiramate is more effective than placebo in maintaining weight reduction in obese patients following intensive non-drug weight reduction program. During the initial 8 weeks, the doses of topiramate or placebo will be gradually increased to the target doses (either 96mg or 192mg) daily by mouth and the doses will be maintained for one year.

Inclusion Criteria:

• Body Mass Index (BMI) >= 33 and < 50 kg/m2
• BMI >=30 and < 50 kg/m2 if patients have controlled hypertension or abnormal blood lipids
• Stable weight
• Female patients must be postmenopausal for at least 1 year, surgically incapable of childbearing, practicing abstinence, or practicing an acceptable method of contraception (requires negative pregnancy test)
• Randomization criteria: Weight reduction of more than 8% of enrollment body weight during the eight week run-in phase

Exclusion Criteria:

• Prior exposure, known contraindication, or hypersensitivity to topiramate
• Exposure to any other experimental drug or device within last 30 days
• A diagnosis of diabetes (except those diagnosed during the enrollment if no medications are needed)
• History or evidence of clinically significant liver disease, cardiovascular disease, uncontrolled hypertension or high thyroid levels
• History of obesity with known cause
• History or family history of kidney stones
• History of weight loss surgery or liposuction
• History of malignancy within last 5 years
• History of an eating disorder