Abstracts

Rationale: As with other antiepileptic drugs (AEDs), the perampanel (PER) US Prescribing Information contains a class warning on suicidal behavior and ideation. Results based on adverse event (AE) reporting from PER Phase II and III double-blind (DB) and open-label studies in patients with partial seizures show that treatment-emergent adverse events (TEAEs) related to suicidality occur in ≤1.1% of patients taking PER. Study 332 is a DB, randomized study conducted to evaluate the efficacy and safety of adjunctive PER treatment in patients ≥12yrs old with uncontrolled PGTCS. This analysis reviews suicidal behavior and ideation in Study 332, using both AE reporting and the Columbia Suicide Severity Rating Scale (C-SSRS).Methods: In Study 332, subjects ≥12yrs old had a clinical diagnosis of PGTCS and were taking 1-3 concomitant AEDs. Following a baseline period (4 or 8wks), subjects were randomized into PER or placebo (PBO) groups for the DB treatment phase (titration, 4wks; maintenance, 13wks), with a maximum PER dose of 8mg. Suicidal behaviors and ideations (based on Suicide and Self-injury Standardized Medical Dictionary for Regulatory Activities [MedDRA] queries [SMQs]) were recorded as TEAEs. Using standard C-SSRS methodology, an assessment of suicidal ideation and behavior was performed at baseline and at every scheduled visit, including after the last dose of study drug.Results: Each of the 163 subjects randomized and treated (PER: N=81; PBO: N=82) had ≥1 postbaseline safety assessment. AE reporting indicated that 2(2.5%) PER- and 3(3.7%) PBO-treated subjects experienced TEAEs related to suicidal ideation and behavior, which led to discontinuation in 2 PER- and 2 PBO-treated subjects. There were no deaths due to TEAEs related to suicidal ideation and behavior. The On-Treatment Suicidality Reports based on binary (yes/no) responses to the C-SSRS categories indicated that the proportion of subjects who reported ≥1 positive suicide-related ideation was lower in the PER group (n=3, 3.7%) than in the PBO group (n=5, 6.1%). There were 2(2.5%) PER- and no PBO-treated subjects reporting ≥1 positive suicide-related behavior on the C-SSRS (1 actual [non-fatal] and 1 aborted suicide attempt). All 3 PER subjects and 2/5 PBO subjects with on-treatment suicidal ideation and/or behavior had a lifetime (prior) history of suicidality at baseline. Incidence of serious treatment-emergent suicidal ideation based on the C-SSRS compared with the 6-month period prior to baseline was 1.3% for PER vs 3.8% for the PBO group. Changes in the severity and intensity of the suicidal ideation C-SSRS score were similar between the PER and PBO groups, and the mean score remained low from prior lifetime baseline to Week 17.Conclusions: Using both AE reporting and the C-SSRS, suicidal behavior and ideation was reported in a few subjects with PGTCS in Study 332 (enrolled subjects, N=163); the data from this small sample size do not suggest any clear difference in suicidality rates between PER and PBO-treated subjects. Patients on AEDs should be monitored for suicidal ideation and behavior. Support: Eisai Inc.