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, here, we present results from a quality of life (QoL) analysis using the Quality of Life in Epilepsy Inventory-31 (QOLIE-31; patients aged ≥ 18 years), and assessment of sleep effect using the Pittsburgh Sleep Quality Index (PSQI; patients aged ≥ 12 years).

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 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. Change in patient-reported QoL (via the QOLIE-31) and change in subjective sleep quality (via the PSQI) at the end of the Maintenance Period (12 months) relative to baseline were exploratory endpoints.

Results: As of March 23, 2021, 23 patients with FOS (n=16) or GTCS (n=7) were included in the Safety Analysis Set, and of these, 12 had completed and 11 had discontinued; most common reason, adverse event (n=5). The mean (standard deviation) change from baseline in overall QOLIE-31 score at the end of Maintenance (12 months) was +3.3 (9.5) for patients with FOS and +7.3 (4.3) for patients with GTCS (Table 1). Across the seven QOLIE-31 subdomains, a minimum clinically important change ( > 11.8) from baseline was seen for emotional well-being (GTCS), medication effects (GTCS), and social function (FOS and GTCS) (Table 1). Patients with FOS or GTCS had poor sleep quality at baseline (defined as a global PSQI score > 5 [includes severe problems in ≥ 2 areas or moderate problems in ≥ 3 areas]); overall, some improvements from baseline in PSQI global score and in some PSQI subdomains were seen with perampanel in patients with FOS or GTCS (Table 2).

Conclusions: These interim results of ELEVATE suggest that perampanel as monotherapy or first add-on may be associated with improvements in QoL, with a clinically important change seen for the subdomain of social function in patients with FOS or GTCS. Overall, perampanel was associated with some improvements in sleep quality (via the PSQI). Additional analyses, involving a larger sample size, 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.