A Study of the Efficacy and Safety of Topiramate in the Prevention of Migraine

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Dose-Response Study to Evaluate the Efficacy and Safety of Topiramate in the Prophylaxis of Migraine

The purpose of this study is to evaluate the safety and efficacy of three doses of topiramate (50 milligrams[mg], 100mg, and 200mg taken daily) compared with placebo in the prevention of migraine.

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the effectiveness and safety of three different doses of topiramate (50mg, 100mg, and 200mg daily) in migraine prophylaxis. The study consists of five phases: baseline (determination of whether patients meet the eligibility criteria and tapering of any migraine medication patients are already taking); initial titration and double-blind phase (8 weeks) which begins with 25 mg/daily increasing to the assigned (50, 100, 200 mg/day topiramate); followed by a maintenance period at the target dose (18 weeks); tapering transition phase (up to 7 weeks); and open-label extension up to 6 months (to a maximum topiramate dose of 1600 mg/day); doses are adjusted to maximize effectiveness and minimize side effects. The primary study hypothesis is that one or more of the three doses of topiramate (50, 100, 200 mg/day) will be superior to placebo in the prophylaxis of migraine based on the change in monthly (28 day) migraine period rate from the prospective baseline period to the double-blind phase and that topiramate treatment is well tolerated. During the titration period (8 weeks), doses are increased to target dose of daily topiramate (50 milligrams[mg], 100, or 200mg) or placebo, taken twice daily by mouth. Doses are continued for 18 weeks, adjusted over 7 weeks, and continued for up to 6 months during the Open-Label Extension.

Inclusion Criteria:

• Medical history consistent with migraine with or without aura according to the International Headache Society (IHS) for at least 6 months prior to the study
• Between 3 to 12 migraine periods and no greater than 15 headache days (migraine and non-migraine) per month during the Baseline Phase
• No clinically significant abnormalities on neurological exams, electrocardiogram (ECG) or clinical laboratory test results at baseline
• 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)

Exclusion Criteria:

• Patients with headaches other than migraine
• Patients with episodic tension or sinus headaches
• Onset of migraine after age of 50 years
• Patients who have failed more than two adequate regimens for migraine prophylaxis
• Patients who overuse pain medications or certain other medications