Abstracts

Rationale: Perampanel, a selective, non-competitive AMPA receptor antagonist, is approved for adjunctive treatment of focal seizures, with or without secondary generalized (SG) seizures, and for primary generalized tonic-clonic seizures in patients with epilepsy aged ?-12 years. Approvals were based on efficacy and safety in double-blind studies, which were followed by open-label extension (OLE) studies. However, antiepileptic drug (AED) monotherapy may be preferable to polytherapy, which has been associated with increased toxicity, non-compliance, and cost. Here we explore the potential of perampanel as monotherapy through evaluation of patients who converted to perampanel monotherapy during OLE studies. Methods: The Phase III studies 304 (NCT00699972), 305 (NCT00699582), and 306 (NCT00700310), and the Phase II study 235 (NCT01161524), evaluated adjunctive perampanel over Double-blind Treatment Phases (6-week Titration; 13-week Maintenance) in patients with refractory focal seizures, with or without SG seizures, despite treatment with 1?"3 AEDs. In studies 304, 305, and 306, patients aged ?-12 years were randomized to receive once-daily placebo, perampanel 8 or 12 mg (studies 304 and 305), or perampanel 2, 4, or 8 mg (study 306). In study 235, patients aged ?-12 to < 18 years were randomized to receive once-daily placebo or perampanel (target dose: 8?"12 mg). Patients from these studies could go on to receive perampanel (up to 12 mg) in the OLE study 307 (patients from studies 304, 305, 306; 16-week blinded Conversion; 256-week Maintenance) or the study 235 OLE Phase (Part A, 33 weeks; Part B, 52 weeks), during which concomitant AEDs could be adjusted. Here we report on patients who were able to discontinue all non-perampanel AEDs and receive perampanel as monotherapy for at least 91 days, and who were able to continue on monotherapy thereafter. Assessments included median percent changes in seizure frequency per 28 days from baseline and monitoring of treatment-emergent adverse events (TEAEs). Results: Figure 1 summarizes treatment details for the seven patients who discontinued all concomitant AEDs and took perampanel as monotherapy (study 307, n=6; study 235 OLE, n=1; female, n=1; age range, 15?"40 years). Figure 2 shows changes in seizure frequency for the patients in study 307 (specific efficacy data unavailable for the patient in study 235 OLE); at their last 13-week time window, these patients all had at least a 50% reduction in seizure frequency compared with baseline (three were seizure free). There were two TEAEs that were reported during perampanel monotherapy and considered probably related to treatment: one moderate event of worsening ataxia (patient 1; study 307), and one mild event of dizziness (patient 4; study 307). One moderate event of dizziness was also reported during perampanel monotherapy but this was ongoing from the polytherapy period (patient 4; study 307). Conclusions: Efficacy and safety data reported for these seven patients may support the use of perampanel as monotherapy for focal seizures. Funding: Eisai Inc.