(567) Open-label Phase 2 Study to evaluate the Interchangeability of the Novel Intravenous Formulation of Perampanel from Oral Tablet in Japanese Patients with Epilepsy (Study E2007-J081-240)

Rationale: Perampanel (PER) is an oral antiseizure medication (ASM), which is characterized by the unique mechanism to inhibit the post-synaptic α‑amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Intravenous infusion formulation of PER has been developed as alternative treatment option for patients when oral administration of PER is not feasible. Study 240 (NCT03754582), a multicenter, uncontrolled, open-label Phase II study was conducted to evaluate the safety and tolerability of 30-minute intravenous infusions of PER as a substitute for oral tablet in patients with focal-onset seizures (FOS) with or without focal to bilateral tonic-clonic seizures (FBTCS) or primary generalized tonic-clonic seizures (PGTCS) in Japan. Here we report the safety, pharmacokinetics and efficacy data from Study 240.

Methods: Study 240 involved patients aged 12 years and older with FOS or PGTCS. This study consisted of 3 phases: the Pretreatment Phase (up to 29 days; oral PER), Treatment Phase (4 days; intravenous PER), and Follow-up Phase (up to 14 days; oral PER). Eligible patients were on a stable dosage (8 to 12 mg/day) of oral PER as an adjunctive therapy with up to 3 marketed concomitant ASMs for at least 28 days before the first intravenous infusion of PER. On Study Day 1, the patients switched from oral tablet to 30-minute intravenous infusion of PER at equivalent daily doses during Treatment Phase. The patients were discharged the day after the last intravenous infusion of PER, and treatment was switched back to their original doses of oral PER.

Results: Twenty-one patients aged 18 to 62 (20 patients with FOS and one patient with FOS and PGTCS) enrolled and received intravenous infusions of PER. Of these, one patient discontinued and 20 patients completed the Treatment Phase. All 21 patients were included in the analysis set. Three (14.3%) patients reported adverse events during the Pretreatment Phase, 15 (71.4%) patients reported treatment-emergent adverse events (TEAEs) during the Treatment Phase, and 6 (28.6%) patients reported TEAEs during the Follow-up Phase. Overall, TEAEs and treatment-related TEAEs were reported in 16 (76.2%) patients and 13 (61.9%) patients, respectively. The most frequently reported TEAEs during the Treatment Phase were dizziness in 6 (28.6%) patients and somnolence in 3 (14.3%) patients, which were all mild in severity and resolved before Follow-up Phase. The mean changes in the maximum plasma concentrations of PER were not higher than 1.4-fold for each dosage by switching from oral tablet to 30-minute intravenous infusion under steady state conditions. In seizure frequency per day, there was no considerable change by switching from oral PER to intravenous PER and back to oral.

Conclusions: Results from Study 240 showed that 30-minute intravenous infusions of PER is an interchangeable to oral PER and intravenous treatment was well-tolerated and efficacious in patients with FOS (with or without FBTCS) or PGTCS.

Funding: Please list any funding that was received in support of this abstract.: Eisai Co., Ltd.