Abstracts

Rationale: In the US/Japan/Korea, perampanel is approved for FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years (monotherapy/adjunctive), and generalized tonic-clonic seizures in patients aged ≥ 12 (≥ 7, Korea) years (adjunctive). This post hoc analysis examines TEAE rates by Treatment Period in patients aged ≥ 12 years with newly diagnosed/currently untreated recurrent FOS, with/without FBTCS, who received perampanel monotherapy during Study 342 (FREEDOM; NCT03201900).

Methods: During the Core Study, patients received perampanel 4 mg/day (4-week Pretreatment; 32-week Treatment [6-week Titration; 26-week Maintenance]). If a patient had a seizure, they could be up-titrated to 8 mg/day (4-week Titration; 26-week Maintenance). Patients could enter an Extension Phase for an additional 26 weeks (total: 52 weeks). TEAE rates were analyzed by Treatment Period (Titration: Weeks 1–3; Steady State: Weeks 4–6; Maintenance: Week 7–end of 4/8-mg/day Maintenance) for 4 and 8 mg/day (for 8 mg/day, titration starts from the first 6-mg/day dose in the 8-mg/day Titration Period). Total perampanel exposure for each Treatment Period, in subject-months, was calculated as the sum of durations of exposure for all patients across that period. TEAE rates were calculated as number of events divided by total exposure, multiplied by 100.

Results: Patient disposition is shown in Figure 1. For these analyses, all 89 treated patients were included in the 4-mg/day group; of these, 21 patients were up-titrated to 8 mg/day and included in the 8-mg/day group. The rate of TEAEs per 100 subject-months was highest during Titration (4 mg/day, 55.0; 8 mg/day, 50.4), lower during steady state (4 mg/day, 25.2; 8 mg/day, 41.0), and at the lowest level during Maintenance (4 mg/day, 15.4; 8 mg/day, 35.1) (Table 1). The same pattern was observed for treatment-related TEAEs and serious TEAEs (which were low overall) with 4 mg/day; rates with 8 mg/day were more variable, which may be due to the small number of patients in this group (n=21). The most common TEAEs per 100 subject-months during Titration (rate of ≥ 10.0) were dizziness (18.3) and somnolence (10.7) at 4 mg/day, and nasopharyngitis (14.4) at 8 mg/day; lower rates of these TEAEs were reported during Steady State and Maintenance vs Titration (Table 1). Some individual TEAEs were reported at lower rates during Titration/Steady State vs Maintenance in both groups, which may be due to the small number of these TEAEs overall leading to fluctuations in the observed patterns. Revised data for this abstract is available on the poster.

Conclusions: Perampanel monotherapy was generally well tolerated for 52 weeks in patients with newly diagnosed/currently untreated recurrent FOS with/without FBTCS. The overall rate of TEAEs was generally highest during Titration and decreased over time with perampanel treatment at both 4 and 8 mg/day. These data are consistent with similar analyses that have been carried out in other Phase III studies of adjunctive perampanel. Following the initial analysis, an error was identified in the data; as such, the revised data will be presented in the poster (please see poster 1.294).

Funding: Please list any funding that was received in support of this abstract.: Eisai Co., Ltd.