Abstracts

Rationale:
In the US and Korea, perampanel is approved for POS (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 (≥ 7, Korea) years. We present a post hoc analysis from FAME (Fycompa as first Add-on to Monotherapy in patients with Epilepsy; Study 412, NCT02726074; South Korea) to assess safety of perampanel by study period and safety and efficacy by dose during the Maintenance Period.
Method:
Patients in FAME were aged ≥ 12 years with POS with/without secondarily generalized seizures (SGS) and had failed treatment with 1 anti-epileptic drug (AED). Perampanel was up-titrated to ≤ 12 mg/day (12 weeks), followed by a 24-week Maintenance Period. Endpoints included 50% responder rates, seizure-freedom rates, median percent reduction in seizure frequency/28 days, and treatment-emergent adverse events (TEAEs). For this analysis, safety data were assessed in the overall population for the Titration vs Maintenance Periods. Safety and efficacy were also assessed by perampanel dose during the Maintenance Period.
Results:
Overall, 85 patients with POS with/without SGS were included in the Full Analysis Set; mean (standard deviation) age, 42.3 (14.1) years. The Safety Analysis Set (SAS) included 102 patients, of which 75.5% (n=77) patients reported 138 TEAEs throughout the study period. The most common (occurring in > 5 patients) TEAEs were 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 the Titration Period vs 24.5% (n=25/102) in the Maintenance Period. In the dose analysis, patients received perampanel 4 mg (n=43), 6 mg (n=27), 8 mg (n=12), 10 mg (n=2), and 12 mg (n=1). 50% responder rates were 93.0% (n=40/43), 81.5% (n=22/27), and 50.0% (n=6/12) with perampanel 4, 6, and 8 mg, respectively; no patients responded at 10 and 12 mg doses (Table 1). Seizure-freedom rates and median percent reduction in seizure frequency/28 days are shown in Table 1. The SAS for the dose analysis included 88 patients; 14 patients in the SAS did not receive study drug during Maintenance and were not included in this group. TEAEs occurred in 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) of patients who received perampanel 4, 6, 8, 10, and 12 mg, respectively. Overall TEAEs and most common TEAEs by perampanel dose are shown in Table 2.
Conclusion:
In this analysis, most TEAEs occurred during the Titration Period, and decreased during the Maintenance Period suggesting improved tolerance once maintenance dose was reached. Efficacy with perampanel was observed across doses. Perampanel was generally well tolerated by all patients regardless of dose. Low patient numbers with higher doses of perampanel should be taken into account when interpreting these data.
Funding:
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Funding:
: Eisai Korea Inc.