S. Palhagen et al., Rufinamide: a double-blind, placebo-controlled proof of principle trial inpatients with epilepsy, EPILEPSY R, 43(2), 2001, pp. 115-124
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.