Abstracts

Rationale: Perampanel (PER), a selective noncompetitive AMPA receptor antagonist, is an antiepileptic drug (AED) approved for adjunctive treatment of partial-onset seizures (POS) in over 35 countries. Pharmacokinetic (PK) properties of various AEDs can be affected by race/ethnicity.¹ This subgroup analysis of the pooled Phase III studies evaluates whether there are differences in PER efficacy and safety based on race. Methods: Patients with refractory POS enrolled in the 3 Phase III studies were aged ≥12yrs and receiving 1-3 concomitant AEDs. Following 6-wk baseline, patients were randomized to 19wks of a once-daily double-blind treatment (6-wk titration, 13-wk maintenance) with placebo (PBO) or PER 8 or 12mg (Studies 304&305); or with PBO or PER 2, 4 or 8mg (Study 306). Patients were recruited from US, Canada, and Australia and countries in Latin America, Africa, Asia and Europe. These study results were pooled (n=1478) and grouped by patient race: White (n=1114), Asian/Pacific Islander (n=289 [Chinese: n=112]), Other (n=44), Black/African American (n=31). Study endpoints included population PK and PK/pharmacodynamic analyses, percent change from baseline in seizure frequency/28 days, responder rate and safety. Because of the small number of subjects in the Black/African American and Other racial subgroups, the principal subgroup analyses of efficacy and safety based on race compare Whites and Asian/Pacific Islanders only. Results: In all racial subgroups, complex partial was the most common seizure type at baseline and most patients were receiving 2 concomitant AEDs. In the population PK model developed for PER based on plasma concentrations obtained in the Phase III studies, there was no significant effect of race on PER clearance and no difference in the concentration-response relationship for PER as a function of race. Improvements in seizure control were seen for therapeutic doses of PER (4-12mg) compared to PBO in both the White and Asian/Pacific Islander subgroups (Fig. 1). The results for the White subgroup were consistent with that described for the overall study population, showing efficacy greater than PBO in all therapeutic doses. For the Asian/Pacific Islander subgroup, efficacy was consistently greater for the PER 8 and 12mg groups than for the PBO group. Very common treatment-emergent adverse events (TEAEs) included dizziness, somnolence, headache, fatigue, irritability and fall (Table 1). There were no notable differences in TEAEs based on race. The proportion of patients who discontinued the study was similar among Whites (PER 16.8% vs PBO 10.1%) and Asian/Pacific Islanders (PER 12.7% vs PBO 10.4%). Conclusions: Race does not appear to affect PER metabolism. The PK of PER was similar between Whites and Asians/Pacific Islanders, with improved seizure control observed for both subgroups. The incidence of very common TEAEs was also comparable. Sample size in the Black/African American or Other racial subgroups was too small to determine if PK, efficacy or safety were different in these subgroups. Ref: 1. Faught E. Epilepsia 2001;42(Supp4):19. Support: Eisai Inc.