A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Difficult to Control Epilepsy
A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Difficult to Control Epilepsy
The purpose of the study is to evaluate the effectiveness and safety of topiramate as add-on
 therapy in patients with difficult to control partial onset seizures who are taking one or
 two standard anti-epileptic drugs.
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).
Inclusion Criteria:

 -  History of simple or complex partial epilepsy that has been documented or witnessed

 -  during a 12-week baseline phase, patient must have at least 12 partial seizures while
 maintaining therapeutic levels of antiepileptic drugs (AEDs)

 -  and have no more than one seizure-free interval of up to 3 weeks and none longer than
 3 weeks

 -  good physical health.

 Exclusion Criteria:

 -  Patients having solely generalized seizures or lacking documentation of partial
 epilepsy

 -  patients with generalized tonic-clonic seizures or other generalized epilepsies in the
 absence of an EEG consistent with partial epilepsy

 -  generalized seizures, which are defined by the EEG wave pattern

 -  seizures that lack an abnormal pulsation pattern on EEG

 -  females who are capable of having children