Abstracts

Rationale: Perampanel (PER), a selective, noncompetitive AMPA receptor antagonist with a novel mechanism of action (MOA), has been approved as adjunctive treatment for partial-onset seizures (POS). The safety and tolerability of PER has been well documented in 3 double-blind (DB), randomized, placebo-controlled phase III trials. Here we present results from a post-hoc analysis comparing patients in pooled PER phase III studies taking concomitant antiepileptic drugs (AEDs) with GABA-enhancing activity (GABAA agonists, GABA uptake inhibitors, or GABA transaminase inhibitors) vs non-GABA acting AEDs (ion channel blockers, glutamate antagonists, SV2A-binding agents, or carbonic anhydrase inhibitors).Methods: Patients with refractory POS enrolled in the phase III trials were aged 12 years and receiving 1-3 concomitant AEDs as background therapy. Following 6-week baseline, patients were randomized to once-daily DB treatment (6-week titration, 13-week 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 grouped by patients on GABA (including benzodiazepines and barbiturates) vs non-GABA AEDs. Efficacy population excluded patients from Latin American sites (N=162 patients) due to a significant treatment-by-region interaction. Efficacy was also limited to the completer population for the GABA group (placebo N=100; PER N=180) and non-GABA group (placebo N=248; PER N=601). Safety included the full intent-to-treat population for the GABA group (placebo N=136; PER N=262) and non-GABA group (placebo N=306; PER N=776). Study endpoints were median percent change from baseline in seizure frequency/28 days, responder rate, and treatment-emergent adverse events (TEAEs). Efficacy and safety results are reported by last dose.Results: Epilepsy-specific medical history characteristics for GABA and non-GABA groups were similar. Efficacy results for patients on concomitant GABA vs non-GABA AEDs are shown in Table 1. Median percent changes in seizure frequency/28 days and responder rates for placebo and PER 2, 4, 8, and 12mg treatment groups were comparable between GABA vs non-GABA subgroups, although the smaller sample size of GABA subgroup was a limitation of this analysis. Percentages and types of TEAEs were not notably different between GABA and non-GABA subgroups. Top 3 TEAEs in the total PER group by decreasing frequency were dizziness, somnolence, and headache for both the GABA and non-GABA subgroups.Conclusions: Efficacy and safety results for PER were consistent for patients on concomitant GABA vs non-GABA AEDs, with both subgroups showing improved seizure control with PER 4 mg, 8 mg, and 12mg relative to placebo. PER is effective and well-tolerated regardless of MOA of background AEDs.