PMID- 24116853
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20220316
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 55
IP  - 1
DP  - 2014 Jan
TI  - Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: 
      results of a phase III, double-blind, randomized, placebo-controlled, 
      flexible-dose trial.
PG  - 38-46
LID - 10.1111/epi.12391 [doi]
AB  - PURPOSE: To evaluate the safety and tolerability of adjunctive brivaracetam 
      (BRV), a high-affinity synaptic vesicle protein 2A (SV2A) ligand, in adults with 
      uncontrolled epilepsy. Efficacy was also assessed in patients with focal seizures 
      as a secondary objective, and explored by descriptive analysis in patients with 
      generalized seizures. METHODS: This was a phase III, randomized, double-blind, 
      placebo (PBO)-controlled flexible dose trial (N01254/NCT00504881) in adults 
      (16-70 years) with uncontrolled epilepsy (up to 20% could be patients with 
      generalized epilepsy). After a prospective 4-week baseline, patients were 
      randomized (3:1) to b.i.d. BRV or PBO, initiated at 20 mg/day and increased, as 
      needed, to 150 mg/day during an 8-week dose-finding period. This was followed by 
      an 8-week stable-dose maintenance period. The treatment period comprised the 
      dose-finding period plus the maintenance period (16 weeks). KEY FINDINGS: A total 
      of 480 patients were randomized (BRV 359, PBO 121); of these, 431 had focal 
      epilepsy and 49 had generalized epilepsy. Ninety percent BRV- and 91.7% 
      PBO-treated patients completed the study. Similar proportions of patients (BRV 
      66.0%, PBO 65.3%) reported adverse events (AEs) during the treatment period. AEs 
      led to treatment discontinuation in 6.1% and 5.0% of BRV- and PBO-treated 
      patients, respectively. The incidence of AEs declined from the dose-finding (BRV 
      56.0%, PBO 55.4%) to the maintenance (BRV 36.8%, PBO 40.9%) period. The most 
      frequent AEs during the treatment period were headache (BRV 14.2% vs. PBO 19.8%), 
      somnolence (BRV 11.1% vs. PBO 4.1%), and dizziness (BRV 8.6% vs. PBO 5.8%). The 
      incidence of psychiatric AEs was similar for BRV and PBO (BRV 12.3%, PBO 11.6%). 
      In patients with focal seizures, the baseline-adjusted percent reduction in 
      seizure frequency/week in the BRV group (n = 323) over PBO (n = 108) was 7.3% (p 
      = 0.125) during the treatment period. The median percent reduction in 
      baseline-adjusted seizure frequency/week was 26.9% BRV versus 18.9% PBO (p = 
      0.070), and the >/=50% responder rate was 30.3% BRV versus 16.7% PBO (p = 0.006). 
      In patients with generalized seizures only, the number of seizure days/week 
      decreased from 1.42 at baseline to 0.63 during the treatment period in 
      BRV-treated patients (n = 36), and from 1.47 at baseline to 1.26 during the 
      treatment period in PBO-treated patients (n = 13). The median percent reduction 
      from baseline in generalized seizure days/week was 42.6% versus 20.7%, and the 
      >/=50% responder rate was 44.4% versus 15.4% in BRV-treated and PBO-treated 
      patients, respectively. SIGNIFICANCE: Adjunctive BRV given at individualized 
      tailored doses (20-150 mg/day) was well tolerated in adults with uncontrolled 
      epilepsy, and our results provided support for further evaluation of efficacy in 
      reducing focal and generalized seizures.
CI  - Wiley Periodicals, Inc. (c) 2013 International League Against Epilepsy.
FAU - Kwan, Patrick
AU  - Kwan P
AD  - Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales 
      Hospital, The Chinese University of Hong Kong, Hong Kong, China; Departments of 
      Medicine and Neurology, The University of Melbourne, Royal Melbourne Hospital, 
      Melbourne, Victoria, Australia.
FAU - Trinka, Eugen
AU  - Trinka E
FAU - Van Paesschen, Wim
AU  - Van Paesschen W
FAU - Rektor, Ivan
AU  - Rektor I
FAU - Johnson, Martin E
AU  - Johnson ME
FAU - Lu, Sarah
AU  - Lu S
LA  - eng
SI  - ClinicalTrials.gov/NCT00504881
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131003
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Pyrrolidinones)
RN  - U863JGG2IA (brivaracetam)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Anticonvulsants/administration & dosage/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Epilepsies, Partial/*drug therapy
MH  - Epilepsy, Generalized/*drug therapy
MH  - Humans
MH  - Middle Aged
MH  - Pyrrolidinones/administration & dosage/adverse effects/*therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Antiepileptic drug
OT  - Brivaracetam
OT  - Epilepsy
OT  - Seizures
OT  - Synaptic vesicle protein 2A
EDAT- 2013/10/15 06:00
MHDA- 2014/04/08 06:00
CRDT- 2013/10/15 06:00
PHST- 2013/08/22 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
AID - 10.1111/epi.12391 [doi]
PST - ppublish
SO  - Epilepsia. 2014 Jan;55(1):38-46. doi: 10.1111/epi.12391. Epub 2013 Oct 3.