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Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial

Objective: The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Methods: Data were pooled from three randomized, placebo-controlled Phase III studies (NCT004900...

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Main Authors: Inoue, Yushi, Tiamkao, Somsak, Zhou, Dong, Cabral-Lim, Leonor, Lim, Kheng Seang, Lim, Shih-Hui, Tsai, Jing-Jane, Moseley, Brian, Wang, Lin, Sun, Weiwei, Hayakawa, Yoshinobu, Sasamoto, Hiroshi, Sano, Tomonobu, Mcclung, Carrie, Bass, Almasa
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Published: Wiley 2024
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R Medicine
Online Access:http://eprints.um.edu.my/45329/
https://doi.org/10.1002/epi4.12929
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spelling my.um.eprints.453292024-10-08T08:26:38Z http://eprints.um.edu.my/45329/ Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial Inoue, Yushi Tiamkao, Somsak Zhou, Dong Cabral-Lim, Leonor Lim, Kheng Seang Lim, Shih-Hui Tsai, Jing-Jane Moseley, Brian Wang, Lin Sun, Weiwei Hayakawa, Yoshinobu Sasamoto, Hiroshi Sano, Tomonobu Mcclung, Carrie Bass, Almasa R Medicine Objective: The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Methods: Data were pooled from three randomized, placebo-controlled Phase III studies (NCT00490035/N01252, NCT00464269/N01253, NCT01261325/N01358) of adults with focal (partial-onset) seizures. Patients taking concomitant levetiracetam were excluded from the efficacy populations, but included in the safety populations. This post-hoc analysis reports data from patients taking BRV in the approved therapeutic range (50-200 mg/day) concomitantly with LTG or TPM. Results: The number of patients in each of the three BRV dosage groups was small, particularly for the TPM subgroup. Mean percent reduction over placebo in baseline-adjusted focal seizure frequency/28 days for BRV 50, 100, and 200 mg/day was 8.7, 5.3, and 8.9 in the LTG subgroup (n = 220), and 8.4, 21.3, and - 4.2 in the TPM subgroup (n = 122). The >= 50% responder rate with concomitant LTG or TPM with BRV 50, 100, and 200 mg/day or placebo was LTG: 28.1%, 36.1%, 34.1%, and 29.1%; and TPM: 14.3%, 44.4%, 25.0%, and 17.5%. There were numerically >= 50%, >= 75%, >= 90%, and 100% responder rates for patients taking BRV >= 50 mg/day compared with placebo in both subgroups. In the LTG and TPM safety populations (n = 245 versus n = 125), treatment-emergent adverse events (TEAEs) were reported with LTG 68.7% versus 68.4%, and TPM 65.6% versus 57.8% (BRV >= 50 mg/day versus placebo). Discontinuations due to TEAEs versus placebo were LTG 7.3% versus 6.3% and TPM 8.2% versus 4.7%. The three most frequently reported TEAEs for both subgroups were somnolence, dizziness, and fatigue. Of these, the incidence of fatigue in the LTG population appeared to increase with dose. Significance: In this post-hoc pooled analysis, BRV administered with concomitant LTG or TPM reduced seizure frequency and was generally well tolerated for BRV doses of 50-200 mg/day. Wiley 2024-06 Article PeerReviewed Inoue, Yushi and Tiamkao, Somsak and Zhou, Dong and Cabral-Lim, Leonor and Lim, Kheng Seang and Lim, Shih-Hui and Tsai, Jing-Jane and Moseley, Brian and Wang, Lin and Sun, Weiwei and Hayakawa, Yoshinobu and Sasamoto, Hiroshi and Sano, Tomonobu and Mcclung, Carrie and Bass, Almasa (2024) Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial. Epilepsia Open, 9 (3). pp. 1007-1020. ISSN 2470-9239, DOI https://doi.org/10.1002/epi4.12929 <https://doi.org/10.1002/epi4.12929>. https://doi.org/10.1002/epi4.12929 10.1002/epi4.12929
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Inoue, Yushi
Tiamkao, Somsak
Zhou, Dong
Cabral-Lim, Leonor
Lim, Kheng Seang
Lim, Shih-Hui
Tsai, Jing-Jane
Moseley, Brian
Wang, Lin
Sun, Weiwei
Hayakawa, Yoshinobu
Sasamoto, Hiroshi
Sano, Tomonobu
Mcclung, Carrie
Bass, Almasa
Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
description Objective: The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Methods: Data were pooled from three randomized, placebo-controlled Phase III studies (NCT00490035/N01252, NCT00464269/N01253, NCT01261325/N01358) of adults with focal (partial-onset) seizures. Patients taking concomitant levetiracetam were excluded from the efficacy populations, but included in the safety populations. This post-hoc analysis reports data from patients taking BRV in the approved therapeutic range (50-200 mg/day) concomitantly with LTG or TPM. Results: The number of patients in each of the three BRV dosage groups was small, particularly for the TPM subgroup. Mean percent reduction over placebo in baseline-adjusted focal seizure frequency/28 days for BRV 50, 100, and 200 mg/day was 8.7, 5.3, and 8.9 in the LTG subgroup (n = 220), and 8.4, 21.3, and - 4.2 in the TPM subgroup (n = 122). The >= 50% responder rate with concomitant LTG or TPM with BRV 50, 100, and 200 mg/day or placebo was LTG: 28.1%, 36.1%, 34.1%, and 29.1%; and TPM: 14.3%, 44.4%, 25.0%, and 17.5%. There were numerically >= 50%, >= 75%, >= 90%, and 100% responder rates for patients taking BRV >= 50 mg/day compared with placebo in both subgroups. In the LTG and TPM safety populations (n = 245 versus n = 125), treatment-emergent adverse events (TEAEs) were reported with LTG 68.7% versus 68.4%, and TPM 65.6% versus 57.8% (BRV >= 50 mg/day versus placebo). Discontinuations due to TEAEs versus placebo were LTG 7.3% versus 6.3% and TPM 8.2% versus 4.7%. The three most frequently reported TEAEs for both subgroups were somnolence, dizziness, and fatigue. Of these, the incidence of fatigue in the LTG population appeared to increase with dose. Significance: In this post-hoc pooled analysis, BRV administered with concomitant LTG or TPM reduced seizure frequency and was generally well tolerated for BRV doses of 50-200 mg/day.
format Article
author Inoue, Yushi
Tiamkao, Somsak
Zhou, Dong
Cabral-Lim, Leonor
Lim, Kheng Seang
Lim, Shih-Hui
Tsai, Jing-Jane
Moseley, Brian
Wang, Lin
Sun, Weiwei
Hayakawa, Yoshinobu
Sasamoto, Hiroshi
Sano, Tomonobu
Mcclung, Carrie
Bass, Almasa
author_facet Inoue, Yushi
Tiamkao, Somsak
Zhou, Dong
Cabral-Lim, Leonor
Lim, Kheng Seang
Lim, Shih-Hui
Tsai, Jing-Jane
Moseley, Brian
Wang, Lin
Sun, Weiwei
Hayakawa, Yoshinobu
Sasamoto, Hiroshi
Sano, Tomonobu
Mcclung, Carrie
Bass, Almasa
author_sort Inoue, Yushi
title Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
title_short Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
title_full Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
title_fullStr Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
title_full_unstemmed Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial
title_sort efficacy, safety, and tolerability of adjunctive brivaracetam in adult asian patients with uncontrolled focal-onset seizures: a phase iii randomized, double-blind, placebo-controlled trial
publisher Wiley
publishDate 2024
url http://eprints.um.edu.my/45329/
https://doi.org/10.1002/epi4.12929
_version_ 1814047541678833664
score 13.211869

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