Abstracts

Rationale: Maintenance of growth and bone health is a complex process with the potential to be influenced by a variety of drugs including antiepileptic drugs (AEDs). Perampanel, 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 perampanel in adolescent pts with inadequately controlled POS. Here we present long-term effects of perampanel on growth and development of adolescent pts from the blinded and OLE phases of study 235.Methods: Pts aged ≥12 to <18 years were randomized (2:1) to once-daily oral perampanel 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 per day) and 13-week Maintenance Period (maximum dose 12 mg/day). Pts completing the blinded phase could receive perampanel in an OLE (6-week conversion plus 27-week maintenance). A further OLE (15–52 weeks) was available in countries without commercially available perampanel or an activated extended-access program. Growth and development was assessed by measuring height and weight, thyroid and insulin-like growth factor-1 (IGF-1) levels, bone age, and Tanner staging.Results: 114 pts (mean age 14.3 years; 58.8% male) entered the OLE phase; 90 pts completed up to 104 weeks’ treatment with perampanel. Mean duration of perampanel exposure for pts in the OLE was 61.3 weeks; mean daily dose was 9.3 (SD 2.0) mg. At baseline, 39.5% of pts were receiving 1 AED, 43.0% 2 AEDs, and 17.5% 3 AEDs. At the end of the OLE phase, the mean weight and height percentile change showed no remarkable change from baseline. For bone age, a slight reduction was observed from baseline (-2 months). These changes were considered reasonable within bone age variance using the Greulich-Pyle method, and thus not deemed clinically important. For Tanner staging, the majority of pts either advanced one stage or remained at the same stage. Although 5 pts receiving perampanel shifted more than one Tanner stage over the course of the study compared with baseline, the first recorded Tanner stage was low for their age and their final recorded Tanner stage was within the expected range for their age; 1 pt receiving placebo shifted more than one Tanner stage. There were no clinically important mean changes compared with baseline in laboratory values for measurements of either thyrotropin or IGF-1 levels. At doses up to 12 mg/day, long-term treatment with perampanel was safe and well tolerated.Conclusions: Compared with baseline, long-term adjunctive perampanel treatment did not have a clinically meaningful effect on growth and development of adolescent pts (≥12 to <18 years) with inadequately controlled POS. Funding: This study was funded by Eisai Inc.