Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
20 Feb 2024
20 Feb 2024
Historique:
revised:
29
11
2023
received:
16
08
2023
accepted:
26
12
2023
medline:
20
2
2024
pubmed:
20
2
2024
entrez:
20
2
2024
Statut:
aheadofprint
Résumé
Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1-3 antiseizure medications in young children with uncontrolled focal (partial-onset) seizures. Double-blind, parallel-group trial (SP0967: NCT02477839/2013-000717-20) conducted between June 2015 and May 2020 at hospitals and clinics in 25 countries. Patients (aged ≥1 month to <4 years) with uncontrolled focal seizures were randomized 1:1 to adjunctive lacosamide or placebo using an interactive voice/web response system and stratified by age. After a 20-day titration period, patients who reached target-dose range (8-12 mg/kg/day) entered a 7-day maintenance period. Region-specific primary efficacy variables were based on ≤72-h video-electroencephalograms: change in average daily frequency (ADF) of electrographic focal seizures as measured on end-of-maintenance video-electroencephalogram versus end-of-baseline video-electroencephalogram (United States); 50% responder rate (≥50% reduction in ADF of focal seizures) during maintenance (European Union). In total, 255 patients were randomized (lacosamide/placebo: 128/127) and received ≥1 trial medication dose. Percentage reduction in ADF of focal seizures for lacosamide (116 patients) versus placebo (120 patients) was 3.2% (95% confidence interval = -13.6 to 17.5, p = 0.69). 50% responder rate was 41.4% for lacosamide (116 patients), 37.5% for placebo (120 patients) (p = 0.58). Treatment-emergent adverse events were reported by 44.5% of lacosamide-treated patients (placebo 51.2%). Adjunctive lacosamide did not show superior efficacy versus placebo in young children with focal seizures. However, efficacy variables were potentially affected by high variability and low reliability between readers in video-electroencephalogram interpretation. Lacosamide was generally well tolerated; safety profile was acceptable and consistent with that in adults and children aged ≥4 years.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : UCB Pharma
Investigateurs
Conceição Campanário da Silva Pereira Almeida
(CC)
Anna Altmann
(A)
Elena Arefieva
(E)
Susan Arnold
(S)
Mihaela Axente
(M)
Maria Giuseppina Baglietto
(MG)
Sophio Bakhtadze
(S)
Domenica Immacolata Battaglia
(DI)
Liudmila Belova
(L)
Marianne Berényi
(M)
Cornelia Calcii
(C)
Dezhi Cao
(D)
Juan Fernando Capristo Gonzales
(JFC)
Hugo Ceja Moreno
(HC)
Yuriy Chomolyak
(Y)
Jo Janette De la Calzada
(JJ)
Anne de Saint Martin
(A)
Dmytro Delva
(D)
Tayard Desudchit
(T)
Gabriella Di Rosa
(G)
Argirios Dinopoulos
(A)
Milda Endziniene
(M)
Viktor Farkas
(V)
Jose Ferreira
(J)
José Carlos Ferreira
(JC)
András Fogarasi
(A)
Cassiano Mateus Forcelini
(CM)
Hadassa Goldberg-Stern
(H)
Tiziana Granata
(T)
Ioana Grigore
(I)
Christian Paul Guzman Astorga
(CPG)
Jose Antonio Infante Cantu
(JAI)
Li Jiang
(L)
Yuwu Jiang
(Y)
Pongkiat Kankirawatana
(P)
Yulia Karakulova
(Y)
Olga Khaletskaya
(O)
Volodymyr Kharytonov
(V)
Heung Dong Kim
(HD)
Ki Joong Kim
(KJ)
Marija Knezevic Pogancev
(MK)
Liudmila Kraeva
(L)
Ruzica Kravljanac
(R)
David Kvernadze
(D)
Alla Kyrychenko
(A)
Volodymyr Kyrychenko
(V)
Wang-Tso Lee
(WT)
Jianmin Liang
(J)
Elmer Guillermo López-Meza
(EG)
Marissa Lukban
(M)
Olga Lvova
(O)
Maša Malenica
(M)
Maria Margherita Mancardi
(MM)
Volodymyr Martyniuk
(V)
Gia Melikishvili
(G)
Richard Morse
(R)
Sylvia Napuri
(S)
Dimitrije Nikolic
(D)
Vilem Novak
(V)
Liliana Maria Nussbaum
(LM)
Claudio Palacios
(C)
Pavel Pilipenko
(P)
Barbara Prawdzic-Senkowska
(B)
Igor Prpic
(I)
Roshan Raja
(R)
Olga Shestakova
(O)
Maria Strachunskaya
(M)
Roberto Alfonso Suástegui Román
(RAS)
Nino Tatishvili
(N)
Salvador Vázquez Fuentes
(SV)
Federico Vigevano
(F)
Gabriela Adriana Visa
(GA)
Yi Wang
(Y)
Elza Márcia Yacubian
(EM)
Jianmin Zhong
(J)
Informations de copyright
© 2024 UCB Biopharma SRL. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Aaberg KM, Gunnes N, Bakken IJ, et al. Incidence and prevalence of childhood epilepsy: a nationwide cohort study. Pediatrics. 2017;139:e20163908.
Mudigoudar B, Weatherspoon S, Wheless JW. Emerging antiepileptic drugs for severe pediatric epilepsies. Semin Pediatr Neurol. 2016;23:167-179.
Kayani S, Sirsi D. The safety and tolerability of newer antiepileptic drugs in children and adolescents. J Cent Nerv Syst Dis. 2012;4:51-63.
UCB Inc. VIMPAT (Lacosamide) US Prescribing Information. 2023 [November 7, 2023]; https://www.ucb-usa.com/vimpat-prescribing-information.pdf
UCB Pharma SA. VIMPAT (Lacosamide) EU Summary of Product Characteristics. 2022 [November 8, 2023]; https://www.ema.europa.eu/en/documents/product-information/vimpat-epar-product-information_en.pdf
Bozorg A, Beller C, Jensen L, et al. Pitfalls of using video-EEG for a trial endpoint in children aged <4 years with focal seizures. Ann Clin Transl Neurol. 2024.
Sheridan PH, Jacobs MP. The development of antiepileptic drugs for children. Report from the NIH workshop, Bethesda, Maryland, February 17-18, 1994. Epilepsy Res. 1996;23:87-92.
Auvin S, French J, Dlugos D, et al. Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: a consensus document from the regulatory task force and the pediatric commission of the International League Against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC). Epilepsia Open. 2019;4:537-543.
Piña-Garza JE, Nordli DR Jr, Rating D, et al. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia. 2009;50:1141-1149.
Mann D, Antinew J, Knapp L, et al. Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: a double-blind, placebo-controlled, video-electroencephalographic trial. Epilepsia. 2020;61:617-626.
Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48:1308-1317.
Chung S, Sperling MR, Biton V, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51:958-967.
Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50:443-453.
Farkas V, Steinborn B, Flamini JR, et al. Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures. Neurology. 2019;93:e1212-e1226.
Chung S, Ben-Menachem E, Sperling MR, et al. Examining the clinical utility of lacosamide: pooled analyses of three phase II/III clinical trials. CNS Drugs. 2010;24:1041-1054.