Abstracts

Rationale: PER is a once-daily oral antiepileptic drug for POS and primary generalized tonic-clonic seizures. Randomized doses of adjunctive PER 4–12 mg/day have previously demonstrated efficacy and tolerability in a pooled analysis of 3 randomized Phase III studies (Studies 304 [NCT00699972]; 305 [NCT00699582]; 306 [NCT00700310]) in patients (pts) aged =12 years with POS, with/without secondarily generalized seizures (SGS) (Steinhoff et al. Epilepsia 2013;54:1481–1489). In a regional (Asia-Pacific), randomized, Phase III Study 335 (NCT01618695) in pts aged =12 years with POS with/without SGS, PER 4 mg/day showed a reduction in the 28-day median seizure frequency, however, this reduction did not reach statistical significance relative to placebo (PBO), which may be due to the refractory population (Nishida et al. Acta Neurol Scand 2018;137:392–399). Here, we report a post hoc pooled analysis of data from these 4 studies based on actual PER dose received, which may have differed from randomized dose, to evaluate the efficacy and safety of adjunctive PER 4 mg/day in pts aged =12 years with POS with/without SGS. Methods: The designs of Studies 304, 305, 306, and 335 have been previously published. In this post hoc analysis, efficacy assessments were based on the Full Analysis Set, which consisted of pts who received PBO or a modal dose of PER 4 mg/day (modal dose represents the actual PER dose that was most frequently received) during the Double-blind Phase of 1 of these 4 studies. Efficacy assessments included median percent reductions in seizure frequency per 28 days from Baseline during the Double-blind Phase and seizure-free status rates during Maintenance for POS (all pts) or SGS (pts who had SGS during Baseline). Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set in pts who were receiving PER 4 mg/day (actual dose) at the onset of their TEAE(s). Results: The Full Analysis Set included 616 pts who received PBO and 363 pts who received a modal dose of PER 4 mg/day (pts with Baseline SGS: n=235 and n=134, respectively). PER 4 mg/day conferred significantly greater median percent reductions in seizure frequency per 28 days for POS and SGS compared with PBO (21.1% vs 12.6% and 49.8% vs 17.4%, respectively; both P<0.001; Figure 1). Seizure-free status rates during Maintenance were also significantly higher with PER 4 mg/day vs PBO for both POS and SGS (3.6% vs 0.8% [P<0.01] and 18.7% vs 11.1% [P<0.05], respectively). In the Safety Analysis Set, TEAEs occurred in 419/1376 (30.5%) pts with POS and 148/499 (29.7%) pts with Baseline SGS who were receiving PER 4 mg/day at the onset of their TEAE(s) (Table 1). The most common TEAE in both seizure groups was dizziness. Conclusions: In this post hoc analysis, adjunctive PER 4 mg/day was shown to be efficacious and well tolerated in pts aged =12 years with uncontrolled POS, including those who had SGS during Baseline. PER 4 mg/day offers an alternative treatment option for pts with uncontrolled POS with/without SGS. Funding: Eisai Inc.