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

Článek v odborném periodiku

Field of Study

30000 3. Medical and Health Sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Keywords in English

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

Abstract

V originále

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

Citovat

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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