A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Difficult to Control Epilepsy

Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain that temporarily disrupt normal brain function. Seizures are classified as "generalized," originating in both sides of the brain simultaneously, or "partial-onset," starting in one area of the brain. Antiepilepsy medications, such as topiramate, are selected based on seizure type. This is a double-blind, placebo-controlled study that includes a baseline phase and a treatment phase. During the baseline phase (12 weeks duration), patients receive one or two of the following standard antiepileptic drugs (AEDs): phenytoin, carbamazepine, phenobarbital, or primidone. Patients who continue to have seizures during treatment with standard AEDs proceed into the double-blind treatment phase. Patients then receive placebo or topiramate at a dosage of 100-milligrams (mg) once daily, increasing to twice daily dosing at a maximum dose of 200 mg/day, 400 mg/day, or 600 mg/day or maximum tolerated dose (depending on treatment group), through Week 16 (total duration of double-blind phase), while continuing on their standard AED regimen. Assessments of effectiveness include the percent reduction in the average monthly seizure rate, percent of patients responding to treatment (having equal to or greater than 50% reduction in seizure rate), and, the patient's and investigator's global assessments of medication at end of study. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, urinalysis), neurologic examinations, and vital sign measurements (blood pressure, pulse, temperature) weekly during the treatment phase. The study hypothesis is that topiramate, taken as add-on therapy to treatment with AEDs, will significantly reduce seizure frequency, compared with placebo, in patients with refractory partial epilepsy and is well-tolerated. Topiramate, 100 milligrams[mg] oral tablets. Dosage begins at 100-mg once daily and increases gradually to twice daily dosing at a maximum dose of 200, 400, or 600 mg/day, and continues through Week 16 (total duration).