Abstracts

Rationale: In the US, perampanel is approved for the treatment of focal-onset seizures (FOS; adjunctive and monotherapy) in patients aged ≥ 4 years, and as adjunctive treatment of generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years. ELEVATE (Study 410; NCT03288129) was a 12-month, multicenter, open-label, Phase IV study where perampanel was prospectively administered as a monotherapy or first adjunctive therapy to patients aged ≥ 4 years with FOS, with or without focal to bilateral tonic-clonic seizures (FBTCS), or GTCS. Using interim data from ELEVATE, we present results for change from baseline in cognition (EpiTrack^®) and depression scores (using the Beck Depression Inventory-II [BDI-II]) by seizure type at 12 months.

Methods: The study consisted of a Screening Period, a Titration Period (≤ 13 weeks), a Maintenance Period (39 weeks), and a 4-week Follow-up. During Titration, patients received perampanel at 2 mg/day, which was titrated to 4 mg/day, with further dose increases (of 2 mg) allowed 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 (EIASM) and weekly for those taking an EIASM. Cognition and depression were exploratory objectives—cognition was assessed using EpiTrack^® (patients ≥ 6 years of age) and depression using the BDI-II (patients ≥ 16 years of age who had completed EpiTrack^®) at baseline, and 3 and 12 months. BDI-II was used to aid interpretation of cognition score.

Results: As of March 23, 2021, 23 patients with FOS (n=16) or GTCS (n=7) were included in the Safety Analysis Set; of these, 12 had completed and 11 had discontinued. The mean (standard deviation [SD]) change from baseline in EpiTrack^® total score at 12 months was -1.4 (4.0) for FOS patients and +1.3 (1.2) for GTCS patients (increase = improvement). Two patients with FOS had an improved shift and two a worsening shift from their baseline EpiTrack^® category at 12 months (improved: n=1 average to excellent; n=1 mildly impaired to average; worsening: n=1 excellent to mildly impaired; n=1 average to mildly impaired). No shifts for patients with GTCS were observed (Table 1). The mean (SD) change from baseline in BDI-II total score at 12 months was +0.7 (8.5) for FOS patients and +4.0 (9.6) for GTCS patients (increase = worsening). One patient with FOS had an improved shift and two patients had a worsening shift (1 patient with FOS and 1 with GTCS) from their baseline BDI-II mood category at 12 months (improved: FOS, mild to minimal; worsening: n=2; FOS, minimal to moderate; GTCS, minimal to mild) (Table 2).

Conclusions: Perampanel did not affect cognition with some patients reporting improvement at 12 months relative to baseline. Overall, there was no clinically relevant worsening of depression, some patients had positive shifts, but the majority stayed within the same mood category. Additional analyses are being conducted and will be included in the presentation.

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