Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures

Objective Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1–3 antiseizure medications in young children with uncontrolled focal (partial‐onset) seizures. Methods Double‐blind, parallel‐group trial (SP0967: NCT02477839/2013‐000717‐20) conducted between June 20...

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Published in:	Annals of clinical and translational neurology Vol. 11; no. 3; pp. 768 - 779
Main Authors:	Makedonska, Iryna, Ng, Yu‐Tze, Beller, Cynthia, Bozorg, Ali, Csikós, János, McClung, Carrie, Moeltgen, Holger, Farkas, Mark Kristof, Silva Pereira Almeida, Conceição Campanário, Altmann, Anna, Arefieva, Elena, Arnold, Susan, Axente, Mihaela, Baglietto, Maria Giuseppina, Bakhtadze, Sophio, Battaglia, Domenica Immacolata, Belova, Liudmila, Berényi, Marianne, Calcii, Cornelia, Cao, Dezhi, Gonzales, Juan Fernando Capristo, Moreno, Hugo Ceja, Chomolyak, Yuriy, De la Calzada, Jo Janette, Saint Martin, Anne, Delva, Dmytro, Desudchit, Tayard, Di Rosa, Gabriella, Dinopoulos, Argirios, Endziniene, Milda, Farkas, Viktor, Ferreira, Jose, Ferreira, José Carlos, Fogarasi, András, Forcelini, Cassiano Mateus, Goldberg‐Stern, Hadassa, Granata, Tiziana, Grigore, Ioana, Astorga, Christian Paul Guzman, Cantu, Jose Antonio Infante, Jiang, Li, Jiang, Yuwu, Kankirawatana, Pongkiat, Karakulova, Yulia, Khaletskaya, Olga, Kharytonov, Volodymyr, Kim, Heung Dong, Kim, Ki Joong, Pogancev, Marija Knezevic, Kraeva, Liudmila, Kravljanac, Ruzica, Kvernadze, David, Kyrychenko, Alla, Kyrychenko, Volodymyr, Lee, Wang‐Tso, Liang, Jianmin, López‐Meza, Elmer Guillermo, Lukban, Marissa, Lvova, Olga, Malenica, Maša, Mancardi, Maria Margherita, Martyniuk, Volodymyr, Melikishvili, Gia, Morse, Richard, Napuri, Sylvia, Nikolic, Dimitrije, Novak, Vilem, Nussbaum, Liliana Maria, Palacios, Claudio, Pilipenko, Pavel, Prawdzic‐Senkowska, Barbara, Prpic, Igor, Raja, Roshan, Shestakova, Olga, Strachunskaya, Maria, Román, Roberto Alfonso Suástegui, Tatishvili, Nino, Fuentes, Salvador Vázquez, Vigevano, Federico, Visa, Gabriela Adriana, Wang, Yi, Yacubian, Elza Márcia, Zhong, Jianmin
Format:	Journal Article
Language:	English
Published:	United States John Wiley & Sons, Inc 01-03-2024 John Wiley and Sons Inc Wiley
Subjects:	Acetamides - adverse effects Adult Anticonvulsants - adverse effects Child Child, Preschool Convulsions & seizures Dose-Response Relationship, Drug Drug Therapy, Combination Electroencephalography Epilepsies, Partial - drug therapy Epilepsy Gestational age Humans Lacosamide - adverse effects Patients Reproducibility of Results Seizures - chemically induced Seizures - drug therapy Treatment Outcome Variables United States > US
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Summary:	Objective Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1–3 antiseizure medications in young children with uncontrolled focal (partial‐onset) seizures. Methods 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). Results 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%). Interpretation 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.
Bibliography:	# in S1 Supplementary Materials . Members of the group are listed in the Acknowledgments section, with further details provided in Appendix ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Members of the group are listed in the Acknowledgments section, with further details provided in Appendix S1 in Supplementary Materials.
ISSN:	2328-9503 2328-9503
DOI:	10.1002/acn3.52004