Adjunctive brivaracetam for uncontrolled focal and generalized
epilepsies: Results of a phase III, double-blind, randomized,
placebo-controlled, flexible-dose trial

J 2014

Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial

KWAN, Patrick; Eugen TRINKA; Wim Van PAESSCHEN; Ivan REKTOR; Martin E. JOHNSON et. al.

Basic information

Original name

Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial

Authors

KWAN, Patrick (344 Hong Kong); Eugen TRINKA (40 Austria); Wim Van PAESSCHEN (56 Belgium); Ivan REKTOR (203 Czech Republic, guarantor, belonging to the institution); Martin E. JOHNSON (840 United States of America) and Sarah LU (840 United States of America)

Edition

Epilepsia, Hoboken, USA, WILEY-BLACKWELL, 2014, 0013-9580

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 4.571

RIV identification code

RIV/00216224:14740/14:00074858

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1111/epi.12391

UT WoS

000329893900006

EID Scopus

2-s2.0-84892932590

Keywords in English

Brivaracetam; Epilepsy; Seizures; Antiepileptic drug; Synaptic vesicle protein 2A

Abstract

In the original language

PurposeTo 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. MethodsThis was a phase III, randomized, double-blind, placebo (PBO)-controlled flexible dose trial (N01254/NCT00504881) in adults (16-70years) 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 20mg/day and increased, as needed, to 150mg/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 (16weeks). Key FindingsA 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. SignificanceAdjunctive BRV given at individualized tailored doses (20-150mg/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.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Cite

KWAN, Patrick; Eugen TRINKA; Wim Van PAESSCHEN; Ivan REKTOR; Martin E. JOHNSON and Sarah LU. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. Hoboken, USA: WILEY-BLACKWELL, 2014, vol. 55, No 1, p. 38-46. ISSN 0013-9580. Available from: https://dx.doi.org/10.1111/epi.12391.

@article{1137362,
   author = {Kwan, Patrick and Trinka, Eugen and Paesschen, Wim Van and Rektor, Ivan and Johnson, Martin E. and Lu, Sarah},
   article_location = {Hoboken, USA},
   article_number = {1},
   doi = {http://dx.doi.org/10.1111/epi.12391},
   keywords = {Brivaracetam; Epilepsy; Seizures; Antiepileptic drug; Synaptic vesicle protein 2A},
   language = {eng},
   issn = {0013-9580},
   journal = {Epilepsia},
   title = {Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial},
   url = {http://onlinelibrary.wiley.com/doi/10.1111/epi.12391/abstract},
   volume = {55},
   year = {2014}
}

TY  - JOUR
ID  - 1137362
AU  - Kwan, Patrick - Trinka, Eugen - Paesschen, Wim Van - Rektor, Ivan - Johnson, Martin E. - Lu, Sarah
PY  - 2014
TI  - Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial
JF  - Epilepsia
VL  - 55
IS  - 1
SP  - 38-46
EP  - 38-46
PB  - WILEY-BLACKWELL
SN  - 00139580
KW  - Brivaracetam
KW  - Epilepsy
KW  - Seizures
KW  - Antiepileptic drug
KW  - Synaptic vesicle protein 2A
UR  - http://onlinelibrary.wiley.com/doi/10.1111/epi.12391/abstract
L2  - http://onlinelibrary.wiley.com/doi/10.1111/epi.12391/abstract
N2  - PurposeTo 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. MethodsThis was a phase III, randomized, double-blind, placebo (PBO)-controlled flexible dose trial (N01254/NCT00504881) in adults (16-70years) 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 20mg/day and increased, as needed, to 150mg/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 (16weeks). Key FindingsA 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. SignificanceAdjunctive BRV given at individualized tailored doses (20-150mg/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.
ER  -

KWAN, Patrick; Eugen TRINKA; Wim Van PAESSCHEN; Ivan REKTOR; Martin E. JOHNSON and Sarah LU. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: Results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. \textit{Epilepsia}. Hoboken, USA: WILEY-BLACKWELL, 2014, vol.~55, No~1, p.~38-46. ISSN~0013-9580. Available from: https://dx.doi.org/10.1111/epi.12391.

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