Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures: a randomized, double-blind, placebo-controlled, parallel-group phase III study.
OBJECTIVE
To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with >or=4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1-2 antiepileptic drugs (AEDs).


METHODS
This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks).


RESULTS
Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56-62% of patients), lamotrigine (25-27%), and valproic acid (22-28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate.


CONCLUSIONS
ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.
Elger
Christian
C
Department of Epileptology, University of Bonn, Bonn, Germany.
Halász
Peter
P
Maia
Joana
J
Almeida
Luis
L
Soares-da-Silva
Patrício
P
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003984:Dibenzazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
D000927:Anticonvulsants; D003984:Dibenzazepines; C416835:eslicarbazepine acetate