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

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the efficacy 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), Double-Blind (patients receive either 50 milligrams[mg], 100mg, 200mg of topiramate, or placebo), Blinded Transition Phase (doses of study medication are adjusted over 7 weeks in preparation for the Open-Label Extension Phase), Open-Label Extension Phase (patients continue the study medication in open-label manner for up to 6 months; doses are adjusted to maximize effectiveness and minimize side effects), Taper/Exit Phase (study medication is slowly discontinued over 2 weeks). 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. Topiramate tablets (50milligrams [mg], 100mg, 200mg, or placebo) taken by mouth as twice-daily regimen during the 26-week Double-Blind Phase. Doses are adjusted and continued during the 6 month Open-Label Extension Phase after which they are tapered over 2 weeks.

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