Abstracts

Rationale: Perampanel is a once-daily oral anti-seizure drug for partial-onset seizures (POS) and primary generalized tonic-clonic seizures. Although the efficacy of perampanel monotherapy has been demonstrated in patients (pts) with refractory epilepsy, the efficacy and safety of perampanel monotherapy is yet to be thoroughly investigated in pts with newly diagnosed epilepsy. Study 342 (NCT03201900; FREEDOM) assessed the efficacy and safety of perampanel monotherapy in pts with newly diagnosed or currently untreated recurrent POS with or without secondarily generalized (SG) seizures in Japan and South Korea. Here, we report efficacy and safety data from the 4 mg/day Treatment Phase as well as the combined 4 mg/day and 8 mg/day Treatment Phases of the Core Study. Methods: Study 342 is an open-label, Phase III study involving pts aged 12-74 years with POS with/without SG seizures. The Core Study consisted of 4-week Pretreatment and 32-week Treatment (6-week Titration; 26-week Maintenance) Phases, and pts were titrated to perampanel 4 mg/day. If pts experienced seizures during the 4 mg/day Maintainance Period, they could enter an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance) and receive perampanel <=8 mg/day. Pts completing the Core Study could enter the Extension. Efficacy endpoints assessed during the 26-week 4 and 8 mg/day Maintenance Periods were: seizure-freedom rate (primary); time to first seizure onset and time to study withdrawal (secondary). Safety endpoints included monitoring treatment-emergent adverse events (TEAEs). Results: A total of 91 pts entered the Treatment Phase; 89 pts received at least one dose of perampanel and were included in the intent-to-treat (ITT) and safety analysis set populations (Japan, n=43; South Korea, n=46). Of the 89 pts, mean age (standard deviation) was 42.1 (18.2) years, 49.4% were female, and 94.4% had newly diagnosed epilepsy with 5.6% having currently untreated recurrent epilepsy. Forty six pts completed the 4 mg/day Treatment Phase, 22 pts discontinued from the study, and 21 pts experienced seizures and entered the 8 mg/day Treatment Phase (8 of whom completed). The mITT Analysis Set comprised 73 pts; median (minimum, maximum) Baseline seizure frequency per 12 weeks was 2.0 (0.9, 21.2) in the mITT population. A summary of efficacy data for the 4 mg/day and combined 4 mg/day and 8 mg/day 26-Week Maintenance Periods of the Core Study is shown in Table 1. Seizure freedom was achieved in 46/73 (63.0%; 95% CI: 50.9-74.0) pts who received perampanel 4 mg/day, and 54/73 (74.0%; 95% CI 62.4-83.5) pts receiving perampanel 4 or 8 mg/day. Perampanel monotherapy was generally well tolerated (Table 2), and dizziness was the most common TEAE reported during the Treatment Phase. Conclusions: Perampanel monotherapy effectively conferred seizure freedom in 63.0% of pts receiving perampanel 4 mg/day and in 74.0% of pts receiving perampanel 4 or 8 mg/day. Treatment was generally well tolerated and results from the 342 Core Study suggest that perampanel monotherapy may be a suitable treatment option for pts aged >