Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline peripd, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria ( p < 0.001, chi-square test).
When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile.
Sachdeo R, Kramer
LD, Rosenberg A, Sachdeo S. Felbamate monotherapy: controlled trial in patients with partial onset seizures. Ann Neurol 1992;32:386-392 Felbamate (FBM), a unique anticonvulsant drug undergoing clinical trials in the United States, was shown to have a profile of efficacy and safety in animal studies that compares very favorably with or is superior to those of existing antiepileptic drugs (AEDs) El, 2). The Antiepileptic Drug Development (ADD) Program, sponsored by the Epilepsy Branch of the National Institute of Neurological Disorders and Stroke (NINDS), evaluated FBM and reported high protective indices (PI) (toxic dose,deffective dose5,,) in both electrically induced and chemically induced seizures 131. The high PIS in combination with the favorable From the '