Felbamate

Abstract

We studied the efficacy and safety of felbamate, an investigational antiepileptic drug, in a unique, double-blind, placebo-controlled trial. Sixty-four patients with refractory partial-onset seizures who completed a routine evaluation for epilepsy surgery met seizure frequency entry criteria. Each patient received felbamate or placebo in addition to the anticonvulsant regimen present at the conclusion of the presurgical evaluation. The treatment phase consisted of an 8-day inpatient period and a 21-day outpatient period. The efficacy variable was time to fourth seizure. The difference in time to fourth seizure was statistically significant (p = 0.028) in favor of felbamate. Eighty-eight percent of the patients in the placebo group had a fourth seizure during the treatment phase compared with 46% of the patients in the felbamate group (p = 0.001). Adverse experiences with felbamate were generally mild or moderate in severity. This trial demonstrated the ability of felbamate to quickly and safely reduce the occurrence of frequent partial-onset seizures and maintain effective seizure control following reductions in the dosages of standard antiepileptic drugs.

Monotherapy Trials of New Antiepileptic Drugs

“…For example, inpatient trials appear to be very useful for demonstrating the efficacy of a study drug as monotherapy in a relatively short period of time and with a relatively small number of patients. Thus far, all concluded trials that use this design (either dose-response or placebo-controlled) have resulted in "positive" trials (1 1, 21,22). These studies are conducted in a controlled environment, the seizure count is well documented, and the risk to patients is minimized by the inclusion of strict exit criteria.…”

Treatment of epilepsy: existing therapies and future developments

“…In recent years, some monotherapy trials have been conducted, in restricted circumstances (264). For example, felbamate was studied in placebo-controlled monotherapy trials in patients following pre-surgical electroencephalographic and video monitoring (295)(296)(297). In these trials, the patients underwent intensive neurodiagnostic monitoring after partial or complete withdrawal from their prior AEDs.…”

Monotherapy Clinical Trials of New Antiepileptie Drugs: Design, Indications, and Controversies

“…In the first presurgical paradigm, patients undergoing seizure recording are randomized into a study at a point during their presurgical evaluation when their usual AED regimen has been withdrawn. After recording of an adequate number of seizures for evaluation purposes, the patients are randomized to receive either placebo or AED (16). Patients are then followed for a period of hours or days and comparisons are made between the time to a prespecified "treatment failure" event, such as the fourth seizure after randomization.…”