Abstracts

Rationale: In the US, perampanel is approved for the treatment of focal-onset seizures (FOS) in patients aged ≥ 4 years (adjunctive/monotherapy) and generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years (adjunctive). ELEVATE (Study 410; NCT03288129) was a multicenter, open-label, Phase IV study of perampanel as monotherapy or first adjunctive therapy in patients aged ≥ 4 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), or GTCS. We present results of treatment-emergent adverse events (TEAEs) from ELEVATE by treatment period and by seizure type.

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/day] were 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. The primary endpoint was retention rate at 3, 6, 9, and 12 months. Secondary endpoints included monitoring of TEAEs.

Results: As of March 23, 2021, 23 patients with FOS (n=16 [FBTCS, n=1]), or GTCS (n=7) were included in the Safety Analysis Set (SAS), and of these 12 had completed and 11 had discontinued. Primary reasons for discontinuation ([n=FOS/FBTCS/GTCS]) were: adverse event (n=2/0/3), lost to follow-up (n=2/1/0), patient choice (n=2/0/0), withdrawal of consent (n=1/0/0), and other (0/0/1). The mean (standard deviation) patient age was 37.8 (17.5), 26.0 (N/A), and 28.3 (9.3) years for patients with FOS, FBTCS, and GTCS, respectively. Overall, 19 patients experienced a TEAE during the Titration Period: 12 (12/16; 75.0%) patients with FOS (with/without FBTCS), and 7 (7/7; 100.0%) patients with GTCS. Of these TEAEs, three reported by two patients with FOS (aggression, anxiety/nightmare) and four reported by three patients with GTCS (dizziness, fatigue, suicidal ideation/worsening depression) led to discontinuation. The TEAEs of suicidal ideation/worsening depression reported by one patient with GTCS were considered serious (perampanel 4 mg/day); the patient was withdrawn from the study but has since recovered from the TEAEs. Additionally, this patient had pre-existing major depression and was taking the anti-depressant citalopram as treatment. Fewer TEAEs were reported during the Maintenance Period: 6 (6/13; 46.2%) patients with FOS and 2 (2/4 50.0%) patients with GTCS; no patients discontinued due to a TEAE and no serious TEAEs were reported. The most common TEAE (≥ 2 patients, any seizure type) during the Titration and Maintenance Periods was fatigue (Table 1).

Conclusions: Most TEAEs occurred during the Titration Period with fewer reported during Maintenance suggesting improved tolerance once the maintenance dose had been reached. 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.