Abstracts

Rationale: Based on the efficacy and safety results of the 3 Phase III double-blind (DB) studies (Studies 304/305/306), perampanel (PER) is approved in >40 countries, including the US and in the EU, for adjunctive treatment of partial seizures with or without secondarily generalized seizures in patients with epilepsy aged ≥12yrs, and in Canada in patients aged ≥18yrs. PER was shown to reduce partial seizure frequency in patients receiving 1-3 concomitant AEDs, in which only 1 CYP3A4 enzyme-inducing AED was allowed. The current subanalysis evaluates the efficacy and safety of PER by baseline AEDs in subjects with uncontrolled PGTCS enrolled in a Phase III DB study (Study 332).Methods: In Study 332, subjects ≥12yrs old had a clinical diagnosis of PGTCS and were taking 1-3 concomitant AEDs (only 1 inducer AED [ie, carbamazepine, oxcarbazepine, or phenytoin] was allowed). Following baseline period (4 or 8 wks), subjects were randomized into PER or placebo (PBO) groups for DB Treatment Phase [Titration, 4 wks; Maintenance, 13 wks], with a maximum dose of 8mg.Results: Each of the 163 subjects (PER: N=81; PBO: N=82) randomized and treated had ≥1 postbaseline safety assessment. Overall, 33.7% of the subjects in the Safety Analysis Set were taking 1 AED, 46.0% were taking 2 AEDs, and 19.6% were taking 3 AEDs, and the distribution was similar for the 2 treatment groups (Table 1). Of the 163 subjects, 27 (16.6%) were taking an inducer AED (22.0% PBO, 11.1% PER). The most frequently used AEDs included valproic acid (VPA or ergenyl chrono), lamotrigine (LTG), levetiracetam (LEV), topiramate (TPM), and zonisamide (ZNS). Results for subjects taking noninducer AEDs demonstrated a larger median percent reduction in PGTCS frequency over the treatment period for the PER group (79.1%) compared with the PBO group (37.3%); however, for the small number of subjects taking inducer AEDs, the reduction in seizure frequency was greater for PBO (41.5%) than for PER (25.4%). For the most common AEDs, there was a larger median percent reduction in PGTCS frequency (over the DB treatment period) and a higher responder rate (Maintenance-LOCF period) for the PER group compared with the PBO group. There was no apparent difference in the overall rate of treatment-emergent adverse events (TEAEs) for the PER group among subjects receiving a baseline inducer AED (61.1% PBO; 88.9% PER) or baseline noninducer AED (75.0% PBO; 81.9% PER). The most frequently reported TEAEs in the PER group (≥10% and with a higher frequency than in the PBO group) were dizziness, fatigue, headache, irritability, and somnolence. TEAEs occurred in similar proportions among subjects taking the most common AEDs.Conclusions: PER treatment improves seizure reduction and is tolerable when used in combination with commonly prescribed AEDs such as VPA, LTG, LEV, ZNS, and TPM, supporting the adjunctive use of PER in patients with PGTCS. In this study, PER treatment did not show improved seizure control when compared with PBO in subjects on inducers, likely due to the small sample size. Support: Eisai Inc.