Abstracts

Rationale: Perampanel (PER), a selective, noncompetitive AMPA receptor antagonist, has been approved as adjunctive treatment for partial-onset seizures (POS). Few epilepsy clinical trials have been performed in the elderly. Here we report the efficacy and safety of PER in the elderly (age 65 yrs) population from a pooled subgroup analysis of the 3 double-blind (DB), randomized, placebo-controlled phase III trials.Methods: Patients with refractory POS aged 12 yrs receiving 1-3 concomitant antiepileptic drugs (AEDs) were enrolled in 3 phase III trials. Following a 6-wk baseline, patients were randomized to once-daily, DB treatment (6-wk titration, 13-wk maintenance) with placebo or PER 8 or 12mg (studies 304 & 305); or with placebo or PER 2, 4, or 8mg (study 306). These study results were pooled and included 28 patients in the 65-yr subgroup (placebo N=8; PER 2mg N=3, 4mg N=1, 8mg N=9, 12mg N=7) in comparison to 1,307 in the 18 to <65-yr (adult) subgroup (placebo N=388; PER 2mg N=156, 4mg N=158, 8mg N=378, 12mg N=227). Study endpoints included percent change from baseline in seizure frequency/28 days, responder rate, population pharmacokinetic (PK) analyses, and safety.Results: Baseline characteristics for the 65-yr subgroup were comparable to the adult subgroup. Complex partial seizures were the most common seizure type experienced by the elderly (89.3%). Stroke etiology was higher in the elderly (7.1%) vs the adult population (1.1%). Given the small number of subjects aged 65 yrs, evaluating differences in efficacy and safety among treatments and between 65 yrs and the adult population has limitations. Efficacy results in 65-yrs and the adult population are shown in Table 1. Compared to placebo, elderly patients were generally responsive to PER treatment, particularly at PER 8 and 12mg doses for median percent changes in seizure frequency/28 days and PER 12mg for responder rates. Population PK showed that PER clearance was not affected by age. Percentages of subjects with any treatment-emergent adverse events (TEAEs) were not notably different across age groups. PER-treated subjects in the elderly subgroup experienced the following very common TEAEs at a higher rate than the adult population (Table 2): dizziness (45%, N=9), fatigue (25%, N=5), and fall (25%, N=5). Serious adverse events (AEs) were reported in 4 patients in the 65-yr subgroup (PER 8mg=1; 12mg=3).Conclusions: Because of increased likelihood for some adverse reactions in the elderly subgroup, dosing titration should proceed slowly in patients aged 65 yrs. However, the amount of data on PER use in the elderly available to guide prescribing is limited.