Abstracts

Rationale: Perampanel (PER), a selective noncompetitive AMPA receptor antagonist, is approved in more than 35 countries for adjunctive treatment of partial-onset seizures (POS) with or without secondarily generalized seizures in patients with epilepsy aged ≥12yrs. This analysis reports short-term effects of PER on growth and development when administered as adjunctive therapy in adolescents (12 to <18yrs) with inadequately controlled POS (in Study 235). Methods: Study 235 was designed to compare effect on cognition of PER vs placebo (PBO) in adolescents. Patients who enrolled in the Phase II study were receiving 1-3 concomitant antiepileptic drugs (AEDs). Following up to 1-wk prospective baseline, patients were randomized to once-daily double-blind treatment (6-wk titration, 13-wk maintenance) with PBO or PER 2mg/day uptitrated weekly in 2mg increments to a target dose range of 8-12mg/day, with a 4-wk follow-up for patients not entering the open-label extension (OLE). Analysis of growth and development was a secondary outcome and included weight and height percentiles calculated from z-scores based on Centers for Disease Control and Prevention growth charts; treatment-emergent adverse events (TEAEs) related to growth and development; thyroid and insulin-like growth factor-1 (IGF-1) laboratory testing; hand x-ray for bone age; and Tanner staging. Results: Adolescent population consisted of 133 patients (PER=85; PBO=48); mean age was 14.3yrs and 53 (39.8%) patients were female (PER=33; PBO=20). Baseline mean weight was 54.7kg for PER and 55.9kg for PBO patients; mean height was 161.8cm for PER and 161.2cm for PBO. Baseline mean weight percentile was slightly lower for PER (46.1%) than PBO (49.9%) and remained slightly lower by end of treatment (PER=48.0%; PBO=49.1%) (Fig. 1). Baseline mean height percentile was slightly lower for PER (44.1%) than PBO (47.5%) and was still lower by end of treatment (PER=43.4%; PBO=47.7%). TEAE of weight decreased was reported in 0 PER and 1 (2.1%) PBO patient; weight increase was reported in 5 (5.9%) PER and 0 PBO patients. There were minimal or no changes from baseline in thyrotropin, free thyroxine, and free triiodothyronine, with no difference between treatments. IGF-1 decreased minimally with PER treatment (-1.1µg/L) and to a greater extent with PBO (-13.9µg/L). Mean change in bone age minus actual age from baseline to end of treatment was similar for PER and PBO (PER=-0.6mos, PBO=-0.9mos), indicating no negative effect of PER vs PBO. Tanner staging results showed progression to higher stages in 5 (15.6%) females and 10 (21.7%) males in the PER group [vs 1 (5.6%) female, 3 (11.5%) males in PBO] and no patients regressing; thus, PER does not negatively affect sexual development in males or females. Conclusions: Adjunctive PER therapy in adolescents with POS showed no overall short-term effects on growth and development relative to PBO. Long-term effect of PER on growth and development is currently being evaluated in the OLE. Support: Eisai Inc.