A Study of the Efficacy and Safety of Topiramate as add-on Therapy in the Treatment of Epilepsy Patients With Difficult to Treat, Partial-onset Seizures.
A Study of the Efficacy and Safety of Topiramate as add-on Therapy in the Treatment of Epilepsy Patients With Difficult to Treat, Partial-onset Seizures.
The purpose of the study is to evaluate the efficacy and safety of topiramate in epilepsy
 patients with difficult to treat, 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 is a double-blind, placebo-controlled study to evaluate topiramate
 efficacy and safety as add-on therapy in partial epilepsy patients. This study 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 once daily, increasing gradually
 over 3 weeks to 2 tablets twice daily (400 mg/day) or maximum tolerated dose, and maintained
 on that dose for 8 weeks (11 weeks is the total duration of the 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 (or placebo). Dosage begins at 100 mg once daily and increases gradually over 3 weeks
 to 2 tablets twice daily (400 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

 -  female patients who are pregnant or nursing, or those not using adequate birth control
 if capable of having children