Abstracts

Rationale: To explore retention and reasons for discontinuation in perampanel long-term extension study 307 in 1216 patients, over 300 of whom had received perampanel for at least 2 years.Methods: Patients with pharmacoresistant focal 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. Retention was assessed from the start of the core studies as the survival probability (patients remaining on study drug, as a proportion of those at risk), censoring patients who were still ongoing at data cut-off and those who completed the core trials but did not enter the extension. For patients entering the extension study, numbers discontinuing during the blinded conversion period, and in 13-week intervals for the remainder of the exposure duration, were calculated and the reasons for discontinuation listed. Results: Of the 1480 patients in the safety analysis set for the core trials, 48.8% had discontinued at cut-off, leaving 758 ongoing or censored. After the blinded conversion period, the survival probability was similar between patients who took perampanel in the core and those who converted from taking placebo in the core (Figure 1). Of the 1216 patients who entered the extension, the total exposure at cut-off was 1803 patient-years (median exposure 1.5 years), and 58.5% were ongoing on treatment at cut-off. During the conversion period, 67 patients discontinued from the study (5.5% of 1216, Figure 2), and of these 35 (2.9%) discontinued due to adverse events (AEs) as the primary reason. Other reasons were subject choice, lack of efficacy, and other (lost to follow-up, missing, and administrative/other). The proportion of discontinuations due to AEs peaked in the 13-week period after the blinded conversion (49 of 93 discontinuations, 4.3% overall), and dropped to 2 of 18 discontinuations at 2 years (0.4% overall, weeks 95 107). From week 30 onwards, subject choice was the most common primary reason for discontinuation. Of the individual AEs leading to discontinuation, dizziness was most frequent (n=14 during conversion period, 1.1%); other AEs that led to discontinuation of 4 or more patients in any period were: irritability (n=6, 0.5%), abnormal behaviour (n=5, 0.4%), aggression (n=5, 0.4%), ataxia (n=4, 0.3%), and headache (n=4, 0.3%).Conclusions: Retention was 58.5% at cut-off, after a median of 1.5 years of adjunctive perampanel treatment in this extension study. Whereas the rate of discontinuations due to AEs peaked immediately after the blinded conversion period, patients with longer term (>30 weeks) perampanel treatment had discontinuation rates due to AEs of <3%.