Effect of adjunctive perampanel on daytime sleepiness and quality of life in adults with focal–onset seizures: Post hoc analyses of the AMPA study

Objective: Assess the relationship between subjective daytime sleepiness and therapeutic effect of adjunctive perampanel in a post hoc analysis of AMPA (NCT04257604), a prospective, observational study in Italy. Methods: AMPA included people with epilepsy (PWE) aged >= 12 years with insufficiently controlled focal-onset seizures, with/without focal to bilateral tonic-clonic seizures, on 1-3 baseline anti-seizure medications, who were prescribed adjunctive perampanel. Full Analysis Set (FAS) included PWE (>= 18 years) who received >= 1 perampanel dose, with baseline Epworth Sleepiness Scale (ESS) scores. ESS was administered at baseline and each study visit for <= 12 months. Excessive daytime sleepiness was defined as ESS >= 11 points. Quality of life (QoL) was assessed using QOLIE-31-P. Results: FAS included 202 PWE. Mean (SD) ESS was 6.3 (4.5) at baseline (N = 202) and 6.2 (4.4) at end of treatment (EoT; n = 177); 29 PWE reported >= 4-point decreases from baseline ESS at EoT, while 31 reported >= 4-point increases. Median percent reductions in seizure frequency/28 days from baseline were 85.6% in improved ESS group and 77.6% in worsened ESS group (n = 14 each). At EoT, 14 PWE with no excessive daytime sleepiness reported a mean (SD) QOLIE-31-P score change of + 7.9 (12.9) points while 11 PWE with excessive daytime sleepiness had a mean (SD) change of-3.4 (18.6). Overall incidence of treatment-emergent adverse events was 56.9%; most commonly, dizziness/vertigo (22.8%) and somnolence (8.4%). Conclusion: In the FAS, adjunctive perampanel did not worsen daytime sleepiness for <= 12 months. In a small subset of patients, seizure frequency was reduced, regardless of ESS changes, and mean QoL at EoT was improved for those without excessive daytime sleepiness but declined for those with excessive daytime sleepiness. No new safety signals emerged.