Authors :
Presenting Author: Pavel Vlasov, MD, PhD – Moscow State University of General Medicine and Dentistry named after A.I. Evdokimov, Moscow, Russia
Bettina Schmitz, MD, PhD – Department of Neurology, Vivantes Humboldt Klinikum, Berlin, Germany; Luc Valton, MD, PhD – Hospital, Purpan, University of Toulouse, Toulouse, France; Anna Patten, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK; Ricardo Sáinz-Fuertes, PhD – Eisai Europe Ltd., Hatfield, Hertfordshire, UK
Rationale:
Epilepsy can affect the sleep and quality of life (QoL) of an individual by altering aspects of their health and daily activities/engagements, but anti-seizure medications (ASMs) may also impact QoL and sleep. Study 512 (NCT04252846) enrolled patients aged ≥ 12 years with a history of focal-onset seizures (FOS) or generalized tonic-clonic seizures (GTCS) associated with idiopathic generalized epilepsy (IGE) to receive perampanel as first adjunctive treatment. Perampanel is approved in > 70 countries and territories including Japan, the United States, China, and other countries in Europe and Asia. This analysis of Study 512 examines the effect of perampanel on seizure-freedom, daytime sleepiness, and QoL.Methods:
In the prospective, observational, Phase IV Study 512, patients with FOS or GTCS associated with IGE who had previously received ≤ 2 ASMs were administered 2–12 mg/day of oral perampanel. Patients were observed for ≤ 12 months after treatment initiation. Secondary endpoints included pragmatic seizure-freedom rates (proportion seizure-free in the Full Analysis Set [FAS; patients with ≥ 1 perampanel dose and ≥ 1 post-dose efficacy measurement]) and completer seizure-freedom rates (proportion of seizure-free patients receiving perampanel at the time of assessment [six or twelve months]). Other endpoints included daytime sleepiness and QoL changes in adults (aged ≥ 18 years), assessed through Epworth Sleepiness Scale (ESS) and QoL in Epilepsy Inventory 10 (QOLIE-10) questionnaires, as well as safety outcomes, reported in the Safety Analysis Set (SAS; patients with ≥ 1 perampanel dose and > 1 post-dose safety measurement).
Results:
Of 191 patients enrolled across ≥ 5 European countries, 182 were included in the SAS and 174 in the FAS. Median age was 36 years and 51.6% of patients were female. Table 1 shows completer and pragmatic seizure-freedom rates. Perampanel treatment did not worsen daytime sleepiness scores, which changed from baseline by -0.6 (-2.5 to 1.4 [n=16]) at 6 months and 0.3 (-1.3 to 1.9 [n=21]) at 12 months. Excessive daytime sleepiness rates varied from baseline (Table 2). At six months, one patient shifted from normal (ESS score ≤ 10) to excessive sleepiness (ESS score > 10) and three shifted from excessive to normal sleepiness; at 12 months, two patients shifted from normal to excessive sleepiness and 2 shifted from excessive to normal sleepiness. Perampanel treatment did not worsen QoL outcomes, which changed from baseline by -0.5 (-1.3 to 0.2 [n=8]) at 12 months. Overall, the most common treatment-emergent adverse events were dizziness (10.4%), irritability (8.8%), and somnolence (8.2%).
Conclusions:
In Study 512, patients with FOS or GTCS associated with IGE who received perampanel as first adjunctive treatment demonstrated promising seizure-freedom rates at six and twelve months; the daytime sleepiness and QoL scores did not worsen with treatment. No new safety signals were identified.Funding:
Eisai Inc.; Eisai Ltd.; Eisai Co., Ltd.