To report efficacy and safety data from the perampanel 4 mg/day, and combined perampanel 4 mg/day and 8 mg/day Treatment Phases of the 342 FREEDOM Core Study.

Study 342 (NCT03201900; FREEDOM) is an open-label, Phase III study of perampanel monotherapy in patients (aged 12–74 years) with newly diagnosed or currently untreated recurrent POS, with or without secondarily generalized seizures (SGS), in Japan and South Korea.

The Core Study comprised 4-week Pretreatment and 32-week Treatment (6-week Titration; 26-week Maintenance) Phases, with titration to perampanel 4 mg/day. If patients experienced seizures during the 4 mg/day Maintenance Period, they could enter an additional 30-week Treatment Phase (4-week Titration; 26-week Maintenance) of perampanel ≤8 mg/day. Efficacy endpoints were: seizure-freedom rate (primary), and time to first seizure onset and to study withdrawal (secondary). Safety endpoints included treatment-emergent adverse events (TEAEs).

Of 91 patients who entered the Treatment Phase, 89 received >1 dose of perampanel (safety/intent-to-treat [ITT] populations; Japan, n=43; South Korea, n=46; 94.4% newly diagnosed epilepsy). Overall, 73 patients entered the 4 mg/day Maintenance Period and were included in the modified ITT population. Seizure-freedom rate was 63.0% (95% confidence interval [CI] 50.9–74.0) and 74.0% (95% CI 62.4–83.5) for perampanel 4 mg/day and perampanel 4 or 8 mg/day, respectively. Cumulative probability of seizure-onset rate (95% CI) was 30.8% (21.5–43.0) and 18.2% (11.0–29.3), and of withdrawal rate was 23.7% (15.4–35.3) and 23.3% (15.2–34.8) for 4 mg/day and 4 or 8 mg/day, respectively. TEAEs were reported in 57 (64.0%) and 67 (75.3%) patients receiving 4 mg/day and 4 or 8 mg/day, respectively; dizziness was the most common (22.5% and 31.5%, respectively).

Perampanel monotherapy at 4 or 8 mg/day may be a suitable treatment option for patients aged ≥12 years with newly diagnosed or currently untreated recurrent POS with or without SGS.