Abstracts

Rationale: In the US and Japan, perampanel is approved as monotherapy and adjunctive therapy for FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), in patients aged ≥ 4 years, and adjunctive treatment of generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years. Study 311 (NCT02849626) was a multicenter, open-label, single-arm study of once-daily perampanel oral suspension in pediatric patients (aged 4 to < 12 years) with inadequately controlled FOS (with/without FBTCS) or GTCS; in Japan, only patients with FOS were enrolled. Because psychiatric adverse events (AEs) and suicidal behavior have been associated with anti-seizure medications (ASMs), this post hoc analysis assessed the long-term (52 weeks) incidence of psychiatric treatment-emergent AEs (TEAEs) and suicidal ideation/behavior during Study 311 in Japanese pediatric patients.

Methods: Patients who completed the Core Study (4-week Pretreatment; 23-week Treatment) could enter Study Extension A (29-week Maintenance; 4-week Follow-up). Patients in Japan received perampanel doses of 2–12 mg/day. TEAEs, including psychiatric TEAEs, were assessed. Suicidal ideation and behavior were monitored in all patients and clinically significant observations were recorded as TEAEs. Suicidality was also assessed via the Columbia-Suicide Severity Rating Scale (C-SSRS) in patients aged ≥ 6 years at consent/assent.

Results: Overall, 53/65 (81.5%) Japanese patients who enrolled in the Core Study entered Extension A. At Core Study baseline, 18/65 (27.7%) patients reported a history of psychiatric disorders. Psychiatric TEAEs were reported by 19/65 (29.2%) patients during the Core Study and by a total of 20/65 (30.8%) patients during the Core Study and Extension A combined (6 [30.0%] of these patients had a history of psychiatric disorders). Psychiatric TEAE onset mostly occurred in the first 24 weeks of treatment. Exposure-adjusted event rate of psychiatric TEAEs was 3.4 per 100 patient-months (Table). The most common psychiatric TEAEs were irritability (n=12, of whom one had a history of irritability), agitation (n=4), and aggression (n=2) (Table). Two (3.1%) patients without a history of psychiatric disorders discontinued perampanel due to a treatment-related psychiatric TEAE (aggression, n=1; irritability, n=1) and no serious psychiatric TEAEs were reported. No Japanese patients reported a lifetime history of suicidality at baseline or had a positive score on the C-SSRS during perampanel treatment.

Conclusions: Based on the incidence of psychiatric TEAEs during the 311 Core Study and Extension Phase A, long-term use of perampanel in Japanese pediatric patients with FOS (with/without FBTCS) does not increase the frequency of these events, and no on-treatment suicidality was reported in this small population. Findings are consistent with the overall Study 311 population. Similar to other ASMs, patients receiving perampanel should be monitored for signs of psychiatric TEAEs, as recommended in the prescribing information.

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