Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.
OBJECTIVE
This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined.


METHODS
Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase.


RESULTS
In the evaluable patient population, seizure frequency 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 frequency of at least 50% relative to baseline (P=0.096).


RESULTS
Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs).


RESULTS
At steady state, rufinamide reached a peak plasma concentration with a mean time (Tmax) of 3.4 h and a mean half-life (t1/2) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens.


CONCLUSIONS
Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs.
Pålhagen
S
S
Department of Neurology, University Hospital, SE-58185, Linköping, Sweden.
Canger
R
R
Henriksen
O
O
van Parys
J A
JA
Rivière
M E
ME
Karolchyk
M A
MA
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D012640:Seizures / Q000453:epidemiology; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide