(342) Efficacy and Safety of Adjunctive Perampanel for Myoclonic and Absence Seizures: Post Hoc Pooled Analysis of Adult, Adolescent, and Pediatric Patients in Studies 332, 311, and 232
Head of Department, General Epileptology Bethel Epilepsy Center, Mara Hospital, Bielefeld, Germany Bielefeld, Germany
Rationale: In the U.S., perampanel is approved for partial-onset seizures (POS; adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS) in patients aged ≥ 12 years. Some antiseizure medications can exacerbate seizures (e.g., myoclonic and absence) in patients with generalized seizures. Here, we performed a post hoc pooled analysis of Phase III Studies 332 (NCT01393743) and 311 (NCT02849626), and Phase II Study 232 (NCT01527006) to assess the efficacy and safety of adjunctive perampanel for myoclonic and absence seizures in adult, adolescent, and pediatric patients. Methods: In Study 332, adult/adolescent patients (aged ≥ 12 years) with idiopathic generalized epilepsy and PGTCS were randomized to placebo or adjunctive perampanel 8 mg/day (17-week Double-blind Treatment Phase [4-week Titration; 13-week Maintenance]). In Study 311, pediatric patients (aged 4–< 12 years) with POS or PGTCS received open-label perampanel (maximum 16 mg/day; 23-week Treatment Period [11-week Titration; 12-week Maintenance]). In Study 232, pediatric patients (aged 2–< 12 years) with epilepsy received open-label perampanel (maximum 0.18 mg/kg/day; 11-week Treatment Period [7-week Titration; 4-week Maintenance]). For this analysis, data from patients with myoclonic and/or absence seizures during baseline were pooled. Assessments included median percent change in seizure frequency/28 days, 50% responder and seizure-freedom rates, and treatment-emergent adverse events (TEAEs). Results: Of 393 treated patients, 66 patients had myoclonic seizures (placebo, n=23 [mean (standard deviation) age: 28.1 [8.9] years); perampanel, n=43 [18.8 (11.9) years]) and 72 had absence seizures (placebo, n=33 [28.8 (13.2) years]; perampanel, n=39 [21.0 (12.2) years]) at baseline; some patients had both seizure types and so are counted in both groups. During treatment, a reduction in the frequency of myoclonic and absence seizures was observed in both the placebo and perampanel groups (Figure 1). For placebo and perampanel, 50% responder rates were: myoclonic, 60.9% (n=14/23) and 44.2% (n=19/43), respectively; absence, 39.4% (n=13/33) and 38.5% (n=15/39), respectively. Seizure-freedom rates were similar across treatment groups and seizure types: myoclonic, 13.0% (n=3/23; placebo) and 9.3% (n=4/43; perampanel); absence, 12.1% (n=4/33; placebo) and 17.9% (n=7/39; perampanel). TEAE incidence was similar for both seizure types and was slightly higher with perampanel vs placebo; a similar pattern was observed for treatment-related TEAEs and serious TEAEs (Table 1). With perampanel, the most common TEAEs were dizziness and fatigue for both seizure types. Conclusions: Despite small patient numbers, these data suggest adjunctive perampanel does not worsen myoclonic or absence seizures in adult, adolescent, and pediatric patients. Seizure reductions were observed for both seizure types; however, this analysis was not powered to make comparisons between placebo vs. perampanel. Funding: Please list any funding that was received in support of this abstract.:
