Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial.
OBJECTIVE
To explore efficacy and safety/tolerability of adjunctive brivaracetam (BRV), a novel, high-affinity synaptic vesicle protein 2A ligand, which also inhibits neuronal voltage-dependent sodium channels, in patients with refractory partial-onset seizures (POS).


METHODS
This was an exploratory, phase IIb, double-blind, randomized, parallel-group, placebo-controlled, dose-ranging study in patients 16-65 years with epilepsy experiencing > or =4 POS during 4-week baseline despite 1-2 concomitant antiepileptic drugs. Patients were randomized (1:1:1:1) to placebo, BRV 5 mg/day (BRV5), BRV 20 mg/day (BRV20), or BRV 50 mg/day (BRV50), administered BID without uptitration during a 7-week treatment period. Primary efficacy endpoint was POS frequency/week during the treatment period relative to placebo.


RESULTS
A total of 208 patients constituted the intention-to-treat population; 197 completed the study. Estimated percentage reductions over placebo in POS frequency/week were 9.8% (BRV5; p = 0.240), 14.9% (BRV20; p = 0.062), and 22.1% (BRV50; p = 0.004). Median percent reductions from baseline in POS frequency/week were 21.7% (placebo), 29.9% (BRV5; p = 0.086), 42.6% (BRV20; p = 0.014), and 53.1% (BRV50; p < 0.001); > or =50% responder rates were 16.7% (placebo), 32.0% (BRV5; p = 0.047), 44.2% (BRV20; p = 0.002), and 55.8% (BRV50; p < 0.001); seizure freedom rates (POS) during the 7-week treatment period were 1.9% (placebo), 8.0% (BRV5; p = 0.193), 7.7% (BRV20; p = 0.193), and 7.7% (BRV50; p = 0.201). BRV was well-tolerated. Most adverse events were mild to moderate and occurred with similar incidence in placebo and BRV groups, and discontinuations due to treatment-emergent adverse events were infrequent (placebo 3.7%; BRV 2.6%).


CONCLUSIONS
This interventional study provides preliminary Class I evidence that adjunctive BRV was efficacious and well-tolerated in patients aged 16-65 years with POS.
French
J A
JA
NYU Comprehensive Epilepsy Center, New York, NY 10016, USA. jacqueline.french@nyumc.org
Costantini
C
C
Brodsky
A
A
von Rosenstiel
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012640:Seizures / Q000188:drug therapy* / Q000453:epidemiology*; D055815:Young Adult
D011760:Pyrrolidinones; C482793:brivaracetam