Abstracts

Rationale: Approval of PER for adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) was based on the randomized, double-blind, placebo (PBO)-controlled, Phase III Study 332 (NCT01393743) in patients (pts) aged =12 years with idiopathic generalized epilepsy (IGE) and PGTCS (French et al. Neurology 2015;85:950-957). Pts completing the double-blind study could enter an Open-label Extension (OLEx) Phase (NCT02307578). Since some antiepileptic drugs aggravate seizures in IGE, this post hoc analysis assessed the effect of PER on the number of days where pts experienced myoclonic or absence seizures (seizure days) and seizure-free days during the Double-blind and OLEx Phases of Study 332. Methods: The Double-blind Phase of Study 332 has been published as noted. The OLEx Phase comprised a 6-week blinded Conversion Period and =136-week Maintenance Phase (PER =12 mg/day). This post hoc analysis included pts from Study 332 who experienced myoclonic and/or absence seizures during Double-blind Baseline (Double-blind Phase analyses) or Pre-PER Baseline (OLEx Phase analyses). For pts who received PBO during the Double-blind Phase, Pre-PER Baseline includes the Double-blind Phase; for pts who received PER during the Double-blind Phase, Pre-PER Baseline includes the Double-blind Baseline. Efficacy and safety assessments for myoclonic and absence seizures included: number of seizure days and seizure-free days, seizure worsening (increased seizure frequency per 28 days from Double-blind/Pre-PER Baseline), monitoring of treatment-emergent adverse events (TEAEs), and discontinuations. Results: During Double-blind Baseline, myoclonic and/or absence seizures were reported by 47/163 pts (PBO, n=23; PER, n=24) and 60/163 pts (PBO, n=33; PER, n=27), respectively. Discontinuations during the Double-bind Phase included 3 (6.4%) pts with myoclonic seizures (PBO, n=1; PER, n=2) and 10 (16.7%) pts with absence seizures (PBO, n=4; PER, n=6); 4 pts had a worsening of myoclonic and/or absence seizures. Of 138 pts who entered the OLEx, 76 experienced myoclonic (n=46) and/or absence seizures (n=52) during Pre-PER Baseline. Discontinuations during the OLEx Phase included 22 (47.8%) pts with myoclonic seizures and 24 (46.2%) pts with absence seizures. The number of myoclonic and absence seizure days and seizure-free days, and the number of pts with seizure worsening across the Double-blind and OLEx Phases, are shown in Tables 1 and 2, respectively. Across the Double-blind (for both PER and PBO) and OLEx Phases (PER only), median number of seizure days decreased and median number of seizure-free days generally increased for each seizure type. For pts who had myoclonic and/or absence seizures during Baseline, the TEAEs reported during the Double-blind and OLEx Phases of Study 332 were consistent with those reported during the Double-blind Phase for pts with PGTCS. Dizziness was the most common TEAE across both Phases. Conclusions: These data do not indicate any overall worsening of myoclonic or absence seizures following adjunctive PER treatment (=12 mg/day). Funding: Eisai Inc.