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June 30, 2010

Adjunctive brivaracetam for refractory partial-onset seizures
A randomized, controlled trial

August 10, 2010 issue
75 (6) 519-525

Abstract

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 ≥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); ≥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.

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Published In

Neurology®
Volume 75Number 6August 10, 2010
Pages: 519-525
PubMed: 20592253

Publication History

Published online: June 30, 2010
Published in print: August 10, 2010

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Keyword

  1. AED = antiepileptic drug; BRV = brivaracetam; BRV5 = BRV 5 mg/day; BRV20 = BRV 20 mg/day; BRV50 = BRV 50 mg/day; CBZ = carbamazepine; CI = confidence interval; ITT = intention-to-treat; LEV = levetiracetam; OR = odds ratio; POS = partial-onset seizures; TEAE = treatment-emergent adverse event.

Notes

Authors

Affiliations & Disclosures

J.A. French, MD
From the NYU Comprehensive Epilepsy Center (J.A.F.), New York, NY; UCB Pharma SA (C.C., A.B.), Braine-L'Alleud, Belgium; and UCB Pharma Inc. (P.v.R.), Smyrna, GA.
C. Costantini, MSc
From the NYU Comprehensive Epilepsy Center (J.A.F.), New York, NY; UCB Pharma SA (C.C., A.B.), Braine-L'Alleud, Belgium; and UCB Pharma Inc. (P.v.R.), Smyrna, GA.
A. Brodsky, MD
From the NYU Comprehensive Epilepsy Center (J.A.F.), New York, NY; UCB Pharma SA (C.C., A.B.), Braine-L'Alleud, Belgium; and UCB Pharma Inc. (P.v.R.), Smyrna, GA.
P. von Rosenstiel, MD
From the NYU Comprehensive Epilepsy Center (J.A.F.), New York, NY; UCB Pharma SA (C.C., A.B.), Braine-L'Alleud, Belgium; and UCB Pharma Inc. (P.v.R.), Smyrna, GA.
On behalf of the N01193 Study Group
From the NYU Comprehensive Epilepsy Center (J.A.F.), New York, NY; UCB Pharma SA (C.C., A.B.), Braine-L'Alleud, Belgium; and UCB Pharma Inc. (P.v.R.), Smyrna, GA.

Notes

Address correspondence and reprint requests to Dr. Jacqueline A. French, NYU Comprehensive Epilepsy Center, 223 East 34th Street, New York, NY 10016 [email protected]

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  3. Safety and efficacy of brivaracetam in children epilepsy: a systematic review and meta-analysis, Frontiers in Neurology, 14, (2023).https://doi.org/10.3389/fneur.2023.1170780
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  5. The efficacy and tolerability of adjunctive brivaracetam for the treatment of adult epilepsy: An Australian multi-center retrospective real-world observational cohort study, Epilepsy & Behavior, 145, (109287), (2023).https://doi.org/10.1016/j.yebeh.2023.109287
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  6. BRIVEST: A ‘real-world’ observational, single-centre study investigating the efficacy, safety and tolerability of Brivaracetam, Epilepsy & Behavior, 138, (108985), (2023).https://doi.org/10.1016/j.yebeh.2022.108985
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  7. Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil, Neuroscience Bulletin, (2023).https://doi.org/10.1007/s12264-023-01138-2
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  8. Brivaracetam add-on treatment in pediatric patients with severe drug-resistant epilepsy: Italian real-world evidence, Seizure: European Journal of Epilepsy, 102, (120-124), (2022).https://doi.org/10.1016/j.seizure.2022.10.001
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  9. Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam: A retrospective outcome analysis, Seizure, 96, (102-107), (2022).https://doi.org/10.1016/j.seizure.2022.02.007
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  10. Anti-convulsant Agents: Levetiracetam and Brivaracetam, NeuroPsychopharmacotherapy, (3619-3632), (2022).https://doi.org/10.1007/978-3-030-62059-2_301
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