(773) Post Hoc Analysis of Patient Baseline Characteristics and the Most Common Treatment-Emergent Adverse Events with Adjunctive Perampanel During the Titration Period of the FAME Study
Professor Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
Rationale: In the U.S. and Korea, perampanel is approved for POS (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic seizures in patients aged ≥ 12 (≥ 7, Korea) years. We present results of a post hoc analysis from the FAME study (Fycompa as first Add-on to Monotherapy in patients with Epilepsy; Study 412, NCT02726074) that assessed whether patient baseline characteristics (age, sex, comorbidities) are associated with the most commonly reported treatment-emergent adverse events (TEAEs) during Titration, and the potential impact of these TEAEs on response. Methods: Patients in FAME were aged ≥ 12 years with POS with/without secondarily generalized seizures and had failed antiepileptic drug monotherapy. Perampanel was up-titrated to ≤ 12 mg/day (12 weeks), followed by a 24-week Maintenance Period. Endpoints included 50% responder and seizure-freedom rates, and TEAEs. For this analysis, the most common TEAEs were defined as those reported by >5 patients during the Titration Period. Results: The Safety Analysis Set consisted of 102 patients. A total of 64/102 (62.7%) patients experienced a TEAE during the Titration Period. The most common TEAEs reported during Titration ( >5 patients) were dizziness (n=48 [47.1%]), somnolence (n=9 [8.8%]), and headache (n=6 [5.9%]). Table 1 shows the onset week, dose adjustment/dose at TEAE, discontinuations, recovery status, and final perampanel dose for patients reporting dizziness, somnolence, and/or headache. Overall, few patients discontinued due to the TEAEs (< 20% patients with each TEAE). Table 2 gives an overview of baseline age, sex, and comorbidities in patients reporting the most common TEAEs. Baseline comorbidity information was available for 24/48 (50.0%), 5/9 (55.6%), and 3/6 (50.0%) patients reporting dizziness, somnolence, and/or headache, respectively. As shown in Table 2, there was no apparent association observed for age or baseline comorbidities but there was a greater proportion of females than males who reported TEAEs of dizziness, somnolence, and/or headache during Titration. The Full Analysis Set (FAS) comprised 85 patients; 50% responder and seizure-freedom rates for the FAS were 80.0% (n=68/85) and 47.1% (n=40/85), respectively. For patients who reported dizziness (n=37), 50% responder and seizure-freedom rates were 81.1% (n=30/37) and 40.5% (n=15/37), respectively; for patients who reported somnolence (n=9), these were 66.7% (n=6/9) and 44.4% (n=4/9), respectively; and for patients who reported headache (n=3), these were 100.0% (n=3/3) and 66.7% (n=2/3), respectively. Conclusions: The majority of patients with TEAEs of dizziness, somnolence, and headache during the Titration Period completed the study and experienced seizure improvements with adjunctive perampanel. More females than males reported at least one of these TEAEs suggesting a possible association. There was no association between age and comorbidities and the most common TEAEs. Funding: Please list any funding that was received in support of this abstract.:
