Abstracts

Rationale: Perampanel is a once-daily oral antiepileptic drug for partial-onset seizures and PGTC seizures. There is currently limited information from prospective clinical studies on the use of perampanel as monotherapy or early adjunctive therapy since the Phase III registration studies evaluated perampanel as adjunctive therapy in a treatment-resistant patient population. Study 410 (NCT03288129) is the first prospective study of perampanel administered as monotherapy or first adjunctive therapy in patients aged =12 years with partial-onset seizures, with or without secondarily generalized (SG) seizures, or PGTC seizures. Here, we provide an update on the enrollment status of Study 410. Methods: Study 410 is a 12-month, multicenter, open-label, Phase IV study, consisting of Screening (=6 weeks prior to first perampanel dose), Titration (13 weeks), Maintenance (39 weeks), and Follow-up (approximately 4 weeks following last perampanel dose) Periods (Figure 1). It is planned to enroll approximately 300 patients aged =12 years with epilepsy at up to 60 sites across the US and other countries (to be identified). Perampanel will be provided as tablets at the assigned dose and administered orally once daily before bedtime. During Titration, perampanel will be taken at 2 mg/day and initially up-titrated to 4 mg/day based on clinical response and tolerability. Titration beyond 4 mg/day to a maximum dose of 12 mg/day (in 2-mg/day increments at a minimum of 2-week intervals) is optional and based on patient need for additional efficacy. Patients receiving concomitant enzyme-inducing antiepileptic drugs can be up-titrated in increments of 2 mg/day at 1-week intervals. The primary endpoint is retention rate, defined as the proportion of patients remaining on perampanel at 3, 6, 9, and 12 months after treatment initiation, assessed using exposure data. Secondary endpoints include: safety and tolerability of perampanel as monotherapy or first adjunctive therapy; seizure-free status during the Maintenance Period or for 3 or 6 months, for partial-onset, SG, and PGTC seizures; and maximum and final perampanel dose during the Titration and Maintenance Periods, respectively. For efficacy, Baseline seizure counts will be collected retrospectively and prospectively for the 12-week period prior to first dose, and seizure diaries will be used to collect seizure counts during the study. Results: Twenty-two sites have been confirmed in the US; 6 are actively recruiting patients. As of May 17, 2018, 3 patients have been screened and randomized for entry into the study (first patient in August 2017). It is projected that the last patient will be enrolled into the study in January 2019. Conclusions: Study 410 will provide an overview of retention rates, and efficacy and safety data for perampanel administered as monotherapy or first adjunctive therapy in patients (aged =12 years) with partial-onset seizures, with or without SG seizures, or PGTC seizures. Funding: Eisai Inc.