Rufinamide: a double-blind, placebo-controlled proof of principle trial inpatients with epilepsy

Objective: This was the first proof of principle clinical trial assessing t he efficacy and safety of rufinamide as adjunctive therapy in epileptic pat ients. The pharmacokinetic (PK) profile of rufinamide was also determined. Methods: Fifty patients with diagnoses of partial or primary generalized to nic-clonic seizures were enrolled in this 28-day double-blind, placebo-cont rolled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtain ed after administration of single-dose rufinamide prior to and after the Do uble-blind phase. Results: In the evaluable patient population, seizure fre quency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P = 0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequ ency of at least 50% relative to baseline (P = 0.096). Safety: Treatment-em ergent adverse events (AEs) consisted mainly of neurologic signs and sympto ms commonly associated with antiepileptic drugs (AEDs). Pharmacokinetics: A t steady state, rufinamide reached a peak plasma concentration with a mean time (T-max) of 3.4 h and a mean half-life (t(1/2)) of 7.3 h. No autoinduct ion of rufinamide metabolism occurred. Rufinamide did not influence the pla sma concentration of carbamazepine, phenytoin or valproate when added to th ese single AED regimens. Conclusion: Rufinamide has been shown, in this pro of of principle trial, to be safe and effective in reducing seizure frequen cy in epileptic patients with no relevant influence on the metabolism of ot her AEDs. (C) 2001 Elsevier Science B.V. All rights reserved.