Abstracts

Rationale: PER is a once-daily oral antiepileptic drug (AED) for POS and primary generalized tonic-clonic seizures (PGTCS). Study 311 (NCT02849626) assessed safety, tolerability, and efficacy of adjunctive PER for treatment of POS (with/without secondarily generalized seizures [SGS]) or PGTCS in patients aged 4 to ?12 years. Here we report interim safety and efficacy data from a subgroup of patients from the Core Study who did (‘with’) or did not (‘without’) receive concomitant EIAEDs at Baseline. Methods: Study 311 is a global, multicenter, open-label, single-arm study of PER oral suspension in pediatric patients with inadequately controlled POS or PGTCS. The Core Study consists of a 4-week Pre-treatment Period (Screening/Baseline), a 23-week Treatment Period (11 weeks Titration; 12 weeks Maintenance), and a 4-week Follow-up Period. Patients must have been on a stable dose of 1–3 concomitant AEDs, of which a maximum of 1 EIAED (carbamazepine, oxcarbazepine, eslicarbazepine, or phenytoin) was permitted. PER dose was titrated according to clinical response and tolerability to a maximum of 12 mg for non-EIAED patients and a maximum of 16 mg for EIAED patients. Patients were stratified in statistical analyses by presence or absence of concomitant EIAEDs. Results: At data cut-off, 161 patients (EIAED n=45; non-EIAED n=116) were treated with =1 PER dose (mean [standard deviation] patient age 8.2 [2.1] years; female 47.1%). Most patients experienced POS (n=139 [88.5%]; of these 75 [47.8%] had SGS) and 42 (26.8%) had primary generalized seizures at Baseline. Overall, 21.0% of patients were taking 1 AED, 57.3% were taking 2 AEDs, and 21.7% were taking 3 AEDs. Of patients taking an EIAED, the most common were carbamazepine (n=24 [52.2%]) and oxcarbazepine (n=19 [41.3%]). None of the patients with PGTCS were receiving an EIAED, therefore no seizure data are available for this subgroup analysis. A total of 56 patients were ongoing, 77 had completed the Core Study (of whom 73 had entered the Extension Study), and 28 had discontinued. An overview of treatment-emergent adverse events (TEAEs) is presented in Table 1; the most common TEAEs (=10% of patients, any group) were somnolence, nasopharyngitis, dizziness, irritability, pyrexia, and vomiting. In patients with POS (overall and those with SGS), there was an improvement from Baseline in seizure frequency per 28 days with or without EIAEDs (Figure 1). 50% responder rates were similar between patients with and without EIAEDs in patients with POS (47.7% [n=21] and 41.8% [n=38], respectively) and SGS (55.6% [n=5] and 56.8% [n=21]). Seizure-free status was achieved by 11.4% (n=5) with and 12.1% (n=11) without EIAEDs (POS patients); and 0.0% [n=0] with and 24.3% (n=9) without EIAEDs (SGS patients). Conclusions: This interim analysis suggests that daily oral doses of adjunctive PER are generally safe and well tolerated, and efficacious in patients aged 4 to ?12 years with POS with/without SGS regardless of Baseline concomitant EIAED status. Funding: Eisai Inc.