(345) Preliminary Pharmacokinetic (PK) and Safety Data of Adjunctive Perampanel Oral Suspension in Pediatric Patients (Aged >6 to <24 months) with Epilepsy in Study 238
Assistant Professor, Director, Pediatric Epilepsy Monitoring Unit Duke University Hospital, Duke Children’s Health Center, Durham, NC Durham, North Carolina
Rationale: In the U.S., perampanel is approved for partial-onset seizures (adjunctive and monotherapy) in patients aged ≥4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥12 years. Selection of anti-seizure medications (ASMs) for patients aged < 4 years can be difficult due to a lack of clinical studies in this population. The purpose of this abstract is to report preliminary PK and safety/tolerability data from a Phase II clinical study (Study 238; NCT02914314), the first study to evaluate adjunctive perampanel therapy in pediatric patients aged ≥ 1 to < 24 months with epilepsy. Methods: Study 238 is a multicenter, open-label study in the U.S. and Latvia. The Core Study comprises Pretreatment (2 weeks), Treatment (12–16-week Titration; 4-week Maintenance), and Follow-up (4 weeks; for patients not entering the Extension) Periods. The Extension Phase comprises 32–36-week Maintenance and 4-week Follow-up Periods. During the Core Study, perampanel is initiated at 0.5 mg/day and titrated to a maximum of 12 mg/day (patients taking non–enzyme-inducing ASMs [EIASMs]) or 16 mg/day (patients taking EIASMs) based on clinical response and tolerability. Planned enrollment is ≥ 16 patients with evaluable PK data. Endpoints include plasma perampanel levels during the Core Study Maintenance Period (primary) and safety (e.g., treatment-emergent adverse events [TEAEs], safety laboratory tests, vital signs, and ECG). Results: As of January 27, 2020, 18 patients have been screened including five screen failures and 13 eligible patients. Of the 13 eligible patients, perampanel treatment was initiated in 12 patients ( >6 to ≤ 12 months cohort: n=4 [mean (standard deviation [SD]) age, 9.0 (2.2) months; 50.0% female]; >12 to < 24 months cohort: n=8 [mean (SD) age, 19.4 (3.5) months; 75.0% female]). Of these, nine patients have completed the Core Study, two are ongoing, and one discontinued from the study early due to inadequate therapeutic effect. All nine patients who completed the Core Study entered the Extension Phase; seven patients have completed the Extension and two have discontinued (patient choice). Plasma concentrations from the nine patients (aged >6 to < 24 months; eight without and one with an EIASM) with available PK data suggest perampanel exposure is within the range previously observed in adults, adolescents, and older children (≥ 2 years) (Figure 1). TEAEs occurred in 11 (91.7%) patients, of which treatment-related TEAEs occurred in 9 (75.0%) patients (Table 1); most common was upper respiratory tract infection. Serious TEAEs occurred in five (41.7%) patients; most common was seizure (n=2). No patients experienced seizure worsening (≥ 50% or ≥ 100% increase in the frequency) of generalized seizures. Conclusions: These preliminary data suggest that perampanel is safe and well tolerated in pediatric patients with epilepsy aged >6 to < 24 months. Perampanel exposure is within the range observed in patients aged ≥ 2 years and the safety profile to date is consistent with prior clinical studies. Enrollment is ongoing. Funding: Please list any funding that was received in support of this abstract.:
