Safety of adjunctive perampanel by titration/maintenance periods and dose in patients with focal-onset seizures: Post hoc analysis of the FAME study

초록

Purpose: In the US/Korea, perampanel is approved for focal-onset seizures (FOS) (adjunctive/monotherapy) in patients aged ≥4 years, and generalised tonic-clonic seizures (adjunctive) in patients aged ≥12 (≥7, Korea) years. This post hoc analysis of the open-label, single-arm FAME study (NCT02726074) assessed the safety of perampanel by study period/dose. Method: Patients were aged ≥12 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS) and had failed antiepileptic drug monotherapy. First adjunctive perampanel was up-titrated to ≤12 mg/day (12 weeks), followed by a 24-week Maintenance Period. Endpoints included 50% responder/seizure-freedom rates, median percent change in seizure frequency/28 days and treatment-emergent adverse events (TEAEs). For these analyses, safety was assessed during Titration vs Maintenance and safety/efficacy were assessed by perampanel maintenance dose. Results: Overall, 75.5% (77/102) of patients in the Safety Analysis Set reported 138 TEAEs, most commonly dizziness (50.0% [n = 51/102]), somnolence (9.8% [n = 10/102]) and headache (8.8% [n = 9/102]). TEAEs occurred in 62.7% (n = 64/102) of patients during Titration and 24.5% (n = 25/102) during Maintenance. Among 88 patients who received maintenance perampanel 4, 6, 8, 10 or 12 mg/day, TEAE incidences across both study periods were 77.8% (n = 35/45), 75.0% (n = 21/28), 58.3% (n = 7/12), 50.0% (n = 1/2) and 100% (n = 1/1), respectively. In the Full Analysis Set (n = 85), 0/3 patients receiving perampanel 10/12 mg/day achieved ≥50% response, but efficacy at lower maintenance doses was demonstrated by 50% responder rates (4 mg/day, 93.0% [n = 40/43]; 6 mg/day, 81.5% [n = 22/27]; 8 mg/day, 50.0% [n = 6/12]), seizure-freedom rates (4 mg/day, 60.5% [n = 26/43]; 6 mg/day, 44.4% [n = 12/27]; 8 mg/day, 16.7% [n = 2/12]) and median percent reductions in seizure frequency/28 days (4 mg/day, 100.0%; 6 mg/day, 91.9%; 8 mg/day, 45.8%). Conclusion: TEAE rates were lower during Maintenance than Titration, suggesting improved tolerance once maintenance doses were reached. While few patients received high doses, perampanel was otherwise generally well tolerated/efficacious regardless of dose. Funding: Eisai Korea Inc.