A 24-week multicenter, randomized, double-blind, parallel-group, dose-ranging study of rufinamide in adults and adolescents with inadequately controlled partial seizures.
OBJECTIVE
To assess the efficacy, safety, tolerability, and pharmacokinetics of adjunctive rufinamide in adults and adolescents with inadequately controlled partial seizures receiving treatment with one to three concomitant antiepileptic drugs (AEDs).


METHODS
A 24-week multicenter Phase II clinical study was conducted (n=647), comprising a 12-week prospective baseline phase and a 12-week randomized double-blind, parallel-group, five-arm (placebo and rufinamide 200, 400, 800, and 1600mg/day) treatment phase.


RESULTS
The linear trend of dose response for seizure frequency per 28 days in the double-blind treatment phase - the primary efficacy outcome measure - was statistically significant in favor of rufinamide (estimated slope=-0.049, P=0.003; minimally efficacious dose, 400mg/day). Response rates, defined as a >or=50% reduction in seizure frequency per 28 days, also revealed a significant linear trend of dose response (P=0.0019, logistic regression analysis). Adverse events were comparable between placebo and all rufinamide groups except the 1600mg/day group; no safety signals were observed.


CONCLUSIONS
These results suggest that in the dose range of 400-1600mg/day, add-on rufinamide therapy may benefit patients with inadequately controlled partial seizures and is generally well tolerated. These data also suggest that higher doses may confer additional efficacy without adversely affecting safety and tolerability.
Elger
Christian E
CE
Department of Epileptology, University of Bonn Medical Center, Bonn, Germany. christian.elger@ukb.uni-bonn.de
Stefan
Hermann
H
Mann
Allison
A
Narurkar
Milind
M
Sun
Yijun
Y
Perdomo
Carlos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D057194:Intention to Treat Analysis; D008875:Middle Aged; D018579:Patient Selection; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics
D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide