Abstracts

Rationale: With the resistance of seizures to antiepileptic drugs (AEDs) for a number of patients with epilepsy, multiple therapeutic approaches, such as vagal nerve stimulation (VNS),1 have been considered. Perampanel (PER) is approved for adjunctive treatment of partial seizures with or without secondarily generalized seizures and for primary generalized tonic-clonic seizures in patients with epilepsy aged ?-12yrs. This post hoc analysis reports efficacy and safety of PER in subjects with drug-resistant partial seizures with and without concurrent VNS therapy from Phase III clinical studies. Methods: Subjects with drug-resistant partial seizures enrolled in PER Phase III studies were aged ?-12yrs and receiving 1-3 concomitant AEDs. VNS must have been implanted ?-5mos before Visit 1; stimulator parameters were to remain stable. After a 6-wk baseline, subjects were randomized to 19wks of once-daily double-blind (DB) 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). Data were pooled for this post hoc analysis, and efficacy and safety were analyzed by concurrent VNS status. Efficacy endpoints: median percent reduction from baseline in seizure frequency/28 days and responder rate (?-50% reduction in seizure frequency relative to baseline in maintenance-LOCF). Safety endpoints: treatment-emergent adverse events (TEAEs), serious AEs (SAEs), and TEAEs leading to withdrawal. Results: The full intent-to-treat population included: +VNS=129 and ?"VNS=1349. Number of concomitant AEDs at baseline and baseline characteristics were consistent between VNS subgroups, except for time since diagnosis (22.8 vs 18.8yrs) and seizure type rates for simple partial without motor signs (41.1% vs 32.0%), complex partial (93.0% vs 84.8%), and complex partial with secondary generalization (79.8% vs 68.5%) in +VNS vs ?"VNS subjects, respectively. Median baseline seizure frequency was higher in +VNS subjects (PBO=18.1%, PER 2mg=29.2%, 4mg=28.0%, 8mg=17.6%, 12mg=27.3%) vs ?"VNS (PBO=10.2%, PER 2mg=9.8%, 4mg= 9.8%, 8mg=11.6%, 12mg=12.1%). During the DB phase, similar reductions in seizure frequency/28 days were observed in +VNS and ?"VNS subjects (Fig 1A). Responder rates were also similar in +VNS and ?"VNS subjects (Fig 1B). Higher total rates of TEAEs, SAEs, and TEAEs leading to withdrawal were observed for PER- and PBO-treated +VNS vs ?"VNS subjects (Table 1). Most TEAEs in both VNS subgroups were considered mild or moderate; no deaths were reported. Limitations are the small number of subjects with VNS in this post hoc analysis, which is not powered to show significance between VNS subgroups. Conclusions: In subjects with drug-resistant epilepsy, adjunctive PER 4, 8, and 12mg reduced the occurrence of seizures, regardless of subjects' use of concurrent VNS therapy. Safety data are consistent with and without VNS, with somewhat higher event occurrences for both PER and PBO with VNS. 1. Sharma.JEpilepsyRes2015;5:1 Funding: Support: Eisai Inc.