Rationale: ELEVATE (Study 410; NCT03288129) was a multicenter, open-label, Phase IV study of perampanel monotherapy or first adjunctive therapy in patients aged ≥ 4 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), or GTCS
. Here, we present a post hoc analysis to evaluate the efficacy of perampanel for FOS and GTCS by assessing time to first seizure following perampanel administration using data from ELEVATE.
Methods: The study consisted of Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. Patients who had not previously received treatment with an ASM or were currently receiving monotherapy and wished to switch to another monotherapy or were in need of an additional ASM were included. During Titration, patients received perampanel 2 mg/day, which was titrated to 4 mg/day (further dose increases [of 2 mg] based on response and tolerability; maximum, 12 mg/day). The primary endpoint was retention rate at 3, 6, 9, and 12 months. Secondary endpoints included seizure freedom (Maintenance Period) and safety. Exploratory endpoints (Maintenance Period) included median percent reduction in seizure frequency per 28 days, 50% and 75% responder rates. Time to first seizure onset was assessed in the Full Analysis Set (FAS) using Kaplan–Meier analysis.
Results: The Safety Analysis Set included 54 patients, of whom 22 (40.7%) patients discontinued (primary reasons: adverse event, n=10; lost to follow-up and patient choice, n=3 each; withdrawal of consent, n=1; other, n=5)
. The mean (standard deviation [SD]) daily perampanel dose during the Maintenance Period was 6.4 (2.1) mg. The FAS included 52 patients (FOS, n=37 [FOS with FBTCS, n=9]; GTCS, n=11; FOS+GTCS=4). The median (range) baseline seizure frequency per 28 days was 2.0 (0.7–105.0), and the median percent reduction in seizure frequency per 28 days during the Maintenance Period (last observation carried forward) ranged from 76.1% (FOS) to 100.0% (GTCS). Out of the 52 subjects in FAS, 19 (36.5%) discontinued/completed study without seizures (n=9 stayed in study for > 1 year; n=10 discontinued by 9 months). Among the 33 (63.5%) patients who experienced seizure(s) during the study, the median (95% confidence interval) time to their first seizure was 94 (23, 281) days, irrespective of seizure type. A total of 48 (88.9%) patients experienced at least one treatment-emergent adverse event (TEAE); four (7.4%) patients had serious TEAEs (sudden unexpected death in epilepsy, transient ischemic attack, depression, mental status changes, and suicidal ideation, n=1 each).
Conclusions: This post hoc analysis of ELEVATE showed that perampanel as monotherapy or first adjunctive therapy was efficacious and well tolerated with no new safety signals observed. The findings of median percent reduction in seizure frequency and median time to first seizure support the sustained efficacy of perampanel.
Funding: Eisai Inc.