Abstracts

Rationale: In the U.S., perampanel is approved for focal-onset seizures (FOS), with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years (monotherapy/adjunctive), and generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years (adjunctive). Some anti-seizure medications are known to exacerbate seizures (e.g., myoclonic and absence) thus limiting their use, such as in patients with idiopathic generalized epilepsy (IGE). Previously we have reported on Study 332 that demonstrated long-term treatment with adjunctive perampanel did not worsen myoclonic or absence seizures in patients aged ≥ 12 years with generalized tonic-clonic seizures of IGE. Building on this we performed a post hoc pooled analysis of Phase III Studies 332 (NCT01393743) and 311 (NCT02849626), and Phase II Study 232 (NCT01527006) to assess the effect of adjunctive perampanel on myoclonic or absence seizure-free days.

Methods: In Study 332, adult/adolescent patients (aged ≥ 12 years) with IGE and GTCS were randomized to placebo or adjunctive perampanel 8 mg/day (17-week Double-blind Treatment Phase [4-week Titration; 13-week Maintenance]). During Study 311, pediatric patients (aged 4 to < 12 years) with FOS/GTCS received open-label perampanel (maximum 16 mg/day; 23-week Treatment Period [11-week Titration; 12-week Maintenance]). In Study 232, pediatric patients (aged 2 to < 12 years) with epilepsy received open-label perampanel (maximum 0.18 mg/kg/day; 11-week Treatment Period [7-week Titration; 4-week Maintenance]). In this analysis, data from patients with myoclonic and/or absence seizures during baseline were pooled to assess median percent change in number of seizure-free days/28 days. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs).

Results: Of 393 treated patients, 66 had myoclonic seizures (placebo, n=23 [mean (standard deviation)] age: 28.1 [8.9] years; perampanel, n=43 [18.8 (11.9) years]) and 72 had absence seizures (placebo, n=33 [28.8 (13.2) years]; perampanel, n=39 [21.0 (12.2) years]) at baseline (some patients had both seizure types and so were included in both groups). The median number of seizure-free days/28 days increased from baseline for each seizure type (Figure 1; percent change, myoclonic: 1.48 [perampanel], 0.53 [placebo]; absence: 1.05 [perampanel], 0.44 [placebo]). The incidence of TEAEs and the most commonly reported TEAEs with perampanel were similar for patients with myoclonic seizures and those with absence seizures (Table 1).

Conclusions: The results of this post hoc pooled analysis are consistent with our previous reporting of seizure frequency reductions among patients with myoclonic or absence seizures. A slight increase in seizure-free days from baseline was observed for both perampanel and placebo with numerically higher percentages for perampanel among patients with myoclonic or absence seizures; these data indicate that adjunctive perampanel did not exacerbate these seizure types in adult, adolescent, and pediatric patients with epilepsy.

Funding: Eisai Inc.