Abstracts

Rationale: In the U.S., perampanel is approved for the treatment of FOS in patients aged ≥ 4 years (adjunctive/monotherapy) and GTCS in patients aged ≥ 12 years (adjunctive). 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 of the final data from ELEVATE stratified by modal dose (< 8 mg/day or ≥ 8 mg/day) of perampanel.

Methods: The study consisted of Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4 weeks) Periods. During Titration patients received perampanel at 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). Dose increases were ≥ 2 weeks apart for patients taking a non–enzyme-inducing anti-seizure medication (non-EIASM) and weekly for those taking an EIASM. Exploratory efficacy endpoints included median percent reduction in seizure-frequency/28 days, 50% responder rate, 75% responder rate, and seizure-freedom rate during the Maintenance Period. Safety endpoints included the incidence of treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and TEAEs leading to perampanel dose adjustment.

Results: In the Safety Analysis Set (SAS), 54 patients received perampanel monotherapy/first adjunctive therapy (n=39, low dose [< 8 mg/day]; n=15, high dose [≥ 8 mg/day]); in the Full Analysis Set, 37 patients received low-dose and 15 patients received high-dose perampanel. In the SAS, patients had a mean (standard deviation [SD]) age of 38.4 (17.7) and 38.7 (17.1) years, respectively, and received a mean (SD) daily perampanel dose (Maintenance Period) of 5.3 (1.1) and 8.9 (1.5) mg, respectively. Median reduction from baseline in seizure frequency (last observation carried forward) during the Maintenance Period was 100.0% for low-dose perampanel and 57.2% for high-dose perampanel. Responder rates are presented in Figure 1. Overall, TEAEs were reported in a similar proportion of patients in each of the two dose groups (Table 1).

Conclusions: These data suggest that most patients with insufficiently controlled FOS, with/without FBTCS, respond to adjunctive perampanel < 8 mg/day, although up-titration to ≥ 8 mg/day may be needed for some patients. There were no major differences between low- and high-dose perampanel in terms of safety. Since patients were not randomized by dose group and due to small sample size, the interpretation of these data may be limited. Physicians should monitor patients to assess when the higher doses might be needed.

Funding: Eisai Inc.