A Phase 4, multicenter, prospective, non-interventional, observational study to investigate the effectiveness and safety/tolerability of perampanel when used as first adjunctive therapy in routine clinical practice in people with epilepsy: Study 512

IntroductionStudy 512 aimed to assess the efficacy and safety of perampanel (PER) as the first add-on therapy.MethodsIn this 12-month, prospective, observational, multicenter study, people with epilepsy (PWE) aged ≥12 years with focal-onset seizures or generalized tonic–clonic seizures (GTCS) associ...

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Main Authors: Sergey Burd, Giovanni Assenza, Sofia Quintas, Francisco José Gil López, Jan Wagner, Anna Lebedeva, Pavel Vlasov, Nina Pantina, Anna Patten, Samantha Goldman, Ricardo Sáinz-Fuertes, Marta Torres Arlandis, Stanislas Lagarde, Tobias Sejbaek, Vadim Kharkovsky
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1533767/full
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Summary:IntroductionStudy 512 aimed to assess the efficacy and safety of perampanel (PER) as the first add-on therapy.MethodsIn this 12-month, prospective, observational, multicenter study, people with epilepsy (PWE) aged ≥12 years with focal-onset seizures or generalized tonic–clonic seizures (GTCS) associated with idiopathic generalized epilepsy received PER as the first add-on therapy to antiseizure medication (ASM) monotherapy. The primary efficacy endpoint was the retention rate at 12 months. Other endpoints included change in seizure frequency from baseline; pragmatic seizure freedom rate (proportion of PWE in the full analysis set achieving freedom from all seizures); responder rate (≥50% seizure frequency reduction from baseline), changes from baseline in the 10-item Quality of Life in Epilepsy questionnaire (QOLIE-10) total score, the Epworth Sleepiness Scale (ESS), and the age-corrected EpiTrack and EpiTrack Junior total score; safety/tolerability (treatment-emergent adverse events [TEAEs]); and PER dose.ResultsOf 184 PWE (Safety Set, n = 182; Full Analysis Set, n = 174), 135 (73.4%) completed the 12-month study. The mean PER dose was 4.7 mg/day. Retention rate at 12 months was 74.2% in the overall population, 81.8% in the 12 to <18 years age group, 74.3% in the 18 to <65 years age group, and 66.7% in the ≥65 years age group. Retention rates were similar between PWE with focal-onset seizures (74.5%) and GTCS (75.0%). The median reduction in monthly seizure frequency per 28 days from baseline to 12 months was 78.6% in the overall population, 92.3% in the 12 to <18 age group, 75.0% in the 18 to <65 years age group, and 87.5% in the ≥65 years age group. In the overall population, pragmatic seizure freedom rates at 12 months were 36.2% (all seizures), 34.1% (all focal seizures), and 45.5% (GTCS); the responder rate at 12 months was 64.4% in the overall population. In total, 52.7% of PWE experienced TEAEs, and 12.1% discontinued due to TEAEs. No significant changes were identified from baseline to 12 months in QOLIE-10, ESS, and the age-corrected EpiTrack and EpiTrack Junior scores.ConclusionPER was efficacious for focal and generalized seizures across all age groups and was generally well-tolerated, as demonstrated by the high retention rates at 12 months.
ISSN:1664-2295