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 from an interim analysis that assessed the incidence of suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS).

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 (dose increases [by 2 mg] based on response and tolerability; maximum, 12 mg/day). Safety (including incidence of treatment-emergent adverse events [TEAEs]) was a secondary endpoint. Suicidal ideation and suicidal behavior were monitored throughout the study using the C-SSRS and clinically significant observations were recorded as 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; of these, 12 had completed and 11 had discontinued; most common reason, adverse event (n=5; 2 FOS, 3 GTCS). 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. Based on this small sample size, 4/23 (17.4%) patients (2 FOS and 2 GTCS) reported (≥ 1) positive ideation on the C-SSRS during perampanel treatment (Table); of whom, three had a lifetime history of suicidal ideation. Based on investigator assessment, one of these four patients (GTCS) had an event of suicidal ideation (no lifetime history) that was deemed clinically relevant and recorded as a TEAE. The TEAE was reported during the Titration Period, was considered a serious TEAE, and related to the study drug. The dose of perampanel taken prior to TEAE onset was 4 mg/day. The patient also reported a serious TEAE of worsening depression (on 4 mg/day) although this patient had pre-existing major depression and was taking an antidepressant (citalopram) for this. The patient was discontinued from the study and both the worsening depression and ideation TEAEs have resolved. Interim CSSR-S results are shown in the Table; one patient (GTCS) with a lifetime history of suicidal behavior reported ≥ 1 positive behavior.

Conclusions: Based on this small sample size, the incidence of suicidality following treatment with perampanel was low. No TEAEs of suicidal ideation were recorded for patients with FOS or FBTCS; there was one patient with GTCS who had ≥ 1 positive ideation on the CSSR-S that was recorded as a TEAE. 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.