Abstracts

Rationale: To explore the regional incidence of adverse events (AEs), over 1803 patient years in patients with refractory partial-onset seizures, in perampanel long-term extension study 307, and look at psychiatric AEs in detail.Methods: Patients with refractory partial-onset seizures (despite 1 3 concomitant AEDs) completing one of three randomized, double-blind, placebo-controlled perampanel core studies could enter into this extension study. Patients were uptitrated from placebo or previous perampanel dose to 12 mg/day perampanel (or individual maximum-tolerated dose) in a 16-week blinded conversion period. Data cut-off was October 2011, at which point the study was still ongoing. AE incidence was based on the entire duration of perampanel exposure (starting from either core or extension), and is shown for all patients (N=1216), and also by geographic groupings: North America; Latin America; Europe Middle-East and Africa (EMEA); Indo-Pacific, and China-Pacific. Serious AEs in the psychiatric disorders subject organ class (SOC) were explored for timing of onset, resolution, and previous psychiatric history.Results: There were 1216 patients in the overall safety analysis set: 259 from North America; 132 from Latin America; 540 from EMEA; 149 from Indo-Pacific, and 136 from China-Pacific. After a median exposure of 1.5 years, the majority of patients experienced at least 1 AE (range from 86.5% in EMEA to 98.8% in North America), and discontinuations due to AEs ranged from 12.8% in Indo-Pacific to 22.1% in China-Pacific (Table 1). Dizziness was the most common AE in all regions (range from 28.9% in Indo-Pacific to 75.0% in China-Pacific); regional variation in AE rates may reflect AE reporting differences among regions. In total, 383 patients (31.5%) had at least 1 AE in the psychiatric disorders SOC, and 4 individual AEs in this SOC were seen in 5% of patients during perampanel exposure (depression, 5.4%; insomnia, 5.3%; aggression, 5.1%; anxiety, 5.0%). Psychiatric AEs were serious in 47 patients (3.9%), 18 of whom had histories of previous psychiatric disorders. The most common serious psychiatric AE was aggression (n=12, 0.99%), which started after the end of the conversion period in 4 of these patients.Conclusions: In 1803 patient-years of exposure to perampanel (median 1.5 years), most patients experienced at least 1 AE, and there was minor variation in AE rates across the regions. Individual psychiatric AEs occurred in up to 5.4% of patients, and no individual psychiatric AEs was serious in >1% of patients. With perampanel exposure of up to 3.3 years, there was no evidence of new safety concerns.