Abstracts

Rationale:
For POS, perampanel is approved as monotherapy and adjunctive treatment in patients aged ≥ 4 years in the US and Japan, and as adjunctive treatment in patients aged ≥ 12 years in Europe. We assessed the efficacy and safety of adjunctive perampanel co-administered with levetiracetam in a post hoc pooled analysis of 4 randomized, double-blind, placebo-controlled Phase III Studies (304, 305, 306, and 335) in patients (aged ≥ 12 years) with POS, with or without secondarily generalized seizures, stratified by concomitant EIASM use given its effect on perampanel exposure level.
Method:
Patients receiving perampanel 4–12 mg/day were included. For levetiracetam, analyses were split by patients who were on concurrent use, who had prior use before study entry, or who had never used levetiracetam. EIASMs were defined as carbamazepine, eslicarbazepine, oxcarbazepine, and phenytoin. Efficacy assessments (Full Analysis Set) included 50% responder and seizure-freedom rates. Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.
Results:
The Full Analysis Set included a total of 1386 patients and the Safety Analysis Set included 1389 patients. In patients with EIASMs, 50% responder rates were comparable regardless of levetiracetam use (Figure 1A). In patients with non-EIASMs, 50% responder rates were numerically higher in patients with concurrent levetiracetam use and those who had never used levetiracetam, compared with those with prior levetiracetam use. Seizure-freedom rates were similar across all 3 patient groups, ranging from 2.0% to 5.9% (Figure 1B). Overall, 50% responder and seizure-freedom rates were generally lower in patients with EIASMs vs with non-EIASMs, except in patients with prior use of levetiracetam where similar rates were observed, possibly due to the smaller number of patients in this group compared with the other groups (Figures 1A–B). The incidence of TEAEs was slightly lower with EIASMs vs non-EIASMs in patients with concurrent use of levetiracetam and those who had never used levetiracetam, and was similar in patients who had a prior use of levetiracetam (Table 1); similar trends were observed for treatment-related TEAEs. The rate of serious TEAEs was comparable with EIASMs and non-EIASMs in patients with concurrent use of levetiracetam and those who had never used levetiracetam (range: 4.9% to 6.1%; Table 1), but rates were slightly higher in patients who had prior use of levetiracetam both with EIASMs and non-EIASMs (8.9% and 11.5%, respectively; Table 1). Across subgroups, the most common TEAE was dizziness (23.1% to 46.7%), regardless of EIASM or levetiracetam use (Table 1).
Conclusion:
These data suggest concurrent use of levetiracetam with perampanel does not affect the efficacy and safety of perampanel treatment, regardless of EIASM use. However, patients receiving concomitant EIASMs may require a higher perampanel dose to achieve similar efficacy to patients receiving non-EIASMs.
Funding:
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Funding:
: Eisai Inc.