Abstracts

Rationale:
In the US and Japan, perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 years. Perampanel 4 mg/day has previously shown efficacy and safety in a pooled analysis of randomized, double-blind, Phase III studies. We assessed the long-term efficacy and safety of perampanel 4 mg/day (received as modal dose) in patients (aged ≥ 12 years) with POS (with/without secondarily generalized seizures [SGS]) who participated in the Open-label Extension (OLEx) Phase of Asia-Pacific Study 335 (NCT01618695), stratified by concomitant EIASM use due to its effect on perampanel exposure levels.
Method:
The Core Study comprised 6-week Pre-randomization and 19-week Randomization (6-week Titration; 13-week Maintenance) Periods. The OLEx Phase comprised 4-week Pre-conversion, 6-week Conversion, and at least 46-week Maintenance Periods. For this analysis, patients who received a modal (most frequent) dose of perampanel 4 mg/day were included. Endpoints included median percent change in seizure frequency per 28 days, 50% responder and seizure-freedom rates, and treatment-emergent adverse events (TEAEs). EIASMs were defined as carbamazepine, phenytoin, and oxcarbazepine.
Results:
Overall, 85 patients (mean [standard deviation] age, 34.6 [13.55] years; 58.8% female) received perampanel 4 mg/day (modal dose) during the OLEx Phase; 48 (56.5%) of these patients received concomitant EIASMs and 37 (43.5%) received non-EIASMs. Median percent reductions in seizure frequency per 28 days were higher in patients receiving non-EIASMs compared with EIASMs for both POS (median [95% confidence interval (CI)] difference: 28.3 [3.7, 54.8]) and SGS (median [95% CI] difference: 16.2 [-54.9, 94.7) (Figure 1A). Fifty-percent responder rates were also greater with non- EIASMs vs EIASMs for POS (relative risk [95% CI]: 4.9 [2.0, 11.9]), but were similar for SGS (relative risk [95% CI]: 0.8 [0.5, 1.5]) (Figure 1B). Seizure-freedom rates were greater with non-EIASMs vs EIASMs for both POS (2.7% [n=1/37] vs 0% [n=0/46]; relative risk [95% CI]: not reported) and SGS (20.0% [n=2/10] vs 6.3% [n=1/16]; relative risk [95% CI]: 3.9 [1.5, 10.2]). The rate of TEAEs and treatment-related TEAEs was slightly higher with non-EIASMs compared with EIASMs, whereas the rate of serious TEAEs was higher with EIASMs compared with non-EIASMs (statistical significance not reported; Table 1). The most common TEAE was dizziness, regardless of EIASM use (Table 1).
Conclusion:
Long-term adjunctive perampanel received at a modal dose of 4 mg/day is efficacious and generally well tolerated in patients from Asia-Pacific (aged ≥ 12 years) with POS (with/without SGS), regardless of EIASM use. However, patients receiving perampanel in combination with an EIASM may require a higher perampanel dose to achieve similar efficacy with only non-EIASMs.
Funding:
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Funding:
: Eisai Co., Ltd.