Abstracts

Rationale: Perampanel is a once-daily oral antiepileptic drug (AED) for partial-onset seizures (POS) and primary generalized tonic-clonic seizures. The efficacy and tolerability of adjunctive perampanel in patients (pts) with uncontrolled epilepsy despite treatment with up to three AEDs has been demonstrated in three pivotal studies; however, the majority of pts were receiving two or three AEDs during Baseline. FAME (Fycompa as first Add-on to Monotherapy in pts with Epilepsy; Study 412, NCT02726074) investigated the efficacy and safety of perampanel as the first adjunctive therapy in pts aged >=12 years with POS, with or without secondarily generalized seizures. Here, we report the adverse profile of perampanel as first adjunctive therapy during the FAME Study. Methods: FAME was a multicenter, open-label, single-arm, Phase IV study conducted in Korea. Pts were eligible if they required adjunctive therapy after failure to control POS with one AED (at a stable dose for >=8 weeks; dose regimen maintained during study). Pts received perampanel 2 mg/day before up-titration to <=12 mg/day over 12 weeks, followed by a 24-week Maintenance Period. A 4-week Follow-up Period was completed after the last perampanel dose for pts who withdrew. During FAME, safety assessments were based on the Safety Analysis Set (SAS) and included monitoring of treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs; defined as TEAEs for which a relationship with perampanel could not be ruled out), serious adverse events (SAEs), and TEAEs leading to discontinuation. Results: In the SAS (N=102), 77 (75.5%) pts reported 138 TEAEs and 57 (55.9%) reported 90 ADRs. Most common TEAEs were dizziness, somnolence, and headache; most common ADRs were dizziness and somnolence (Table 1). Most TEAEs were mild (n=66 [64.7%]) or moderate (n=16 [15.7%]); 1 (1.0%) pt reported a severe TEAE (seizure). Overall, 48/138 (34.8%), 87/138 (63.0%), and 3/138 (2.2%) TEAEs were considered not related, possibly related, or probably related to study drug, respectively. Neurobehavioral TEAEs included irritability (n=2), anger (n=2), suicidal ideation (n=1), and suicide attempt (n=1); these pts recovered or were in recovery. Eight (7.8%) pts had SAEs (Table 1); 1 SAE (suicidal ideation) was possibly related to study drug. All pts with SAEs recovered. TEAEs led to discontinuation of 14 (13.7%) pts; the most common was dizziness (Table 1). Overall incidences of TEAEs, ADRs, SAEs, and TEAEs leading to discontinuation were generally higher during Titration than Maintenance or Follow-up (Table 1). Overall, 29/138 (21.0%) and 1/138 (0.7%) TEAEs led to dose reduction or temporary interruption of perampanel, respectively; 85/138 (61.6%) TEAEs caused no dose change. Most pts with TEAEs recovered (113/138, 81.9%) or were in recovery (23/138, 16.7%); 2 pts did not recover following dizziness and diplopia. Table 2 shows outcomes for the 3 most common TEAEs following a dose adjustment. Conclusions: These results suggest that perampanel was well tolerated, with the most common TEAEs being dizziness, somnolence, and headache. There were no new safety signals reported during the FAME Study. Most pts recovered from their TEAE(s), and all pts with SAEs recovered. TEAEs were generally reported at a higher incidence during the Titration Period compared with the Maintenance Period, suggesting a slower up-titration schedule may be beneficial to reduce the overall incidence of TEAEs. Funding: Eisai Korea Inc.