A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Epilepsy.
A Study of the Efficacy and Safety of Topiramate in the Treatment of Patients With Epilepsy.
The purpose of this study is to evaluate the effectiveness and safety of topiramate as an
 add-on therapy in patients with uncontrolled partial onset seizures who are taking one or two
 standard antiepileptic 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 study is designed to study patients with partial epilepsy. This is a
 double-blind, placebo-controlled study that includes a baseline phase and a treatment phase.
 During the baseline phase (8 weeks duration), patients receive one or two standard
 antiepileptic drugs (AEDs), such as phenytoin, carbamazepine, phenobarbital, primidone, or
 valproic acid. Patients who continue to have seizures during treatment with standard AEDs
 proceed into the double-blind treatment phase. Patients then receive topiramate or placebo at
 a dosage of 100-milligrams (mg) once daily, increasing gradually to 3 tablets twice daily
 (600 mg/day, maximum) for 12 weeks (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: that is, in patients who
 continue to have seizures despite treatment with a first-line AEDs. In addition, it is
 hypothesized that topiramate is well-tolerated. Topiramate, 100 milligrams (mg) oral tablets.
 Dosage begins at 100 mg once daily and increases gradually over 4 weeks to 3 tablets twice
 daily (600 mg/day, maximum) or maximum tolerated dose for an additional 8 weeks.
Inclusion Criteria:

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

 -  an electroencephalogram (EEG) during the preceding 5 years that has a pattern
 consistent with the diagnosis of partial epilepsy

 -  during an 8-week baseline phase, patient must have at least 8 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 no seizure-free interval 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 pregnant, nursing, or those not using adequate birth control if
 capable of having children