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 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 long-term cognitive effects 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/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. Outcome measures included change from baseline after 52 weeks of PER: Cognitive Drug Research (CDR) System Global Cognition Score (GCS); five core CDR System domains; language (Controlled Oral Word Association Test [COWAT]); manual dexterity skills (Lafayette Grooved Pegboard Test [LGPT]).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 was 61.3 weeks; mean daily dose 9.3 (SD 2.0) mg. Over the blinded and OLE phases (up to 52 weeks), there was a small change in GCS T-score (-1.0) from baseline (-41.3 [SD 12.7]) to end of treatment (40.3 [SD 13.7]; p=0.96); this was not considered clinically relevant. Actual mean T-Scores for the five core CDR System domains are shown (Figure). Power of attention significantly declined over the study compared with baseline (p=0.03); this was thought to be clinically relevant, however, pts showed impairments of over 2 SDs at baseline versus healthy age-matched controls. Compared with baseline, there were no significant changes in continuity of attention (p=0.44), quality of episodic memory (p=0.10), quality of working memory (p=0.46), or speed of memory (p=0.23). PER did not have clinically important effects on language or manual dexterity skills after 52 weeks of PER. For COWAT, there was an overall improvement in mean letter fluency score of 2.2 versus baseline. For LGPT, slight improvements from baseline in mean time to complete the test were visible for the non-dominant hand at all study visits with the exception of Week 9; after 52 weeks of treatment with PER, there was an improvement of -3.3 seconds.Conclusions: Compared with baseline, adjunctive PER had minimal overall cognitive effects in adolescent pts (≥12 to <18 years) with inadequately controlled POS during 52 weeks of treatment with PER. Funding: This study was funded by Eisai Inc.