Abstracts

Rationale: PER, a selective non-competitive AMPA receptor antagonist, is approved in over 40 countries for adjunctive treatment of POS with or without secondarily generalized (SG) seizures in patients (pts) with epilepsy aged ≥12 years (Canada ≥18 years). Study 235, a randomized, double-blind, placebo-controlled, Phase II study with an OLE phase, investigated adjunctive PER in adolescent pts with inadequately controlled POS. Here we present the long-term efficacy and tolerability of adjunctive PER from the blinded and OLE phases of study 235.Methods: Pts aged ≥12 to <18 years were randomized (2:1) to once-daily oral PER or placebo, during a 6-week Titration (2 mg per day and up-titrated weekly in 2 mg increments to a target dose of 8–12 mg/day) and 13-week Maintenance Period (maximum dose 12 mg/day). Pts completing the blinded phase could receive PER in an OLE (6-week conversion and 27-week maintenance). A further OLE (15–52 weeks) was available in countries without commercially available PER or an activated extended-access program. Seizure counts and types were recorded daily by the pt or caregiver up to 52 weeks. All adverse events (AEs) and serious AEs (SAEs) were recorded up to 104 weeks.Results: 114 pts (mean age 14.3 years) entered the OLE phase; 90 pts completed up to 104 weeks’ treatment with PER. Mean duration of PER exposure for pts in the OLE was 61.3 weeks; mean daily dose was 9.3 (SD 2.0) mg. At baseline, pts had simple partial seizures with (34.2%) or without (14.9%) motor symptoms, complex partial seizures (71.9%), partial seizures with SG seizures (49.1%), generalized seizures (0.9%), and unclassified seizures (1.8%). The proportions of pts taking 1, 2, or 3 concomitant antiepileptic drugs were 39.5, 43.0, and 17.5%, respectively. At Weeks 40–52, mean responder rate in the OLE phase was 66.0% and median % change in total seizure frequency relative to baseline -74.1%. Improvement was seen as early as Weeks 1–13 in pts exposed to PER for ≥52 weeks, with a median % change in total seizure frequency relative to baseline of -60.9% and a responder rate of 53.7%. Similar values were obtained for pts exposed to PER for shorter durations. Improved efficacy appeared related to longer PER exposure (≥39 weeks), but there was little difference between pts who had ≥39 vs ≥52 weeks’ exposure. At doses up to 12 mg/day, the safety profile was similar to the blinded phase. Most frequent AEs with PER were dizziness (29.8%) and somnolence (19.3%). 10 pts experienced 11 SAEs possibly related to PER; 2 pts had treatment withdrawn (1 aggression; 1 suicidal ideation), 1 pt had their dose reduced (aggression), and 1 pt had a dose interruption (intentional overdose).Conclusions: Compared with baseline, long-term adjunctive treatment with PER was efficacious and well tolerated in adolescent pts (≥12 to <18 years) with inadequately controlled POS. The results were consistent with previously reported studies. Funding: This study was funded by Eisai Inc.