Rationale: In the U.S., perampanel is approved for the treatment of focal-onset seizures (FOS) in patients aged ≥ 4 years (adjunctive/monotherapy) and generalized tonic-clonic seizures (GTCS) in patients aged ≥ 12 years (adjunctive). ELEVATE (Study 410; NCT03288129) was a multicenter, open-label, Phase IV study of perampanel monotherapy or first adjunctive therapy in patients aged ≥ 4 years with FOS, with/without focal to bilateral tonic-clonic seizures (FBTCS), or GTCS
. Patients with epilepsy can experience behavioral and psychiatric events, and a decline in cognitive function. The change in cognition (EpiTrack
®) for the overall patient population from ELEVATE has been reported previously (mean [standard deviation, SD] change in EpiTrack
® total score at 12 months [n=28] was -0.4 [3.3]). Here, we present a post hoc analysis of change from baseline in cognition (EpiTrack
®) scores, in a subgroup of patients with a history of psychiatric and behavioral events from ELEVATE.
Methods: The study consisted of Screening, Titration (≤ 13 weeks), Maintenance (39 weeks), and Follow-up (4-weeks) Periods. During Titration, patients received perampanel at 2 mg/day, which was titrated to 4 mg/day (further dose increases [of 2 mg] based on response and tolerability; maximum, 12 mg/day). Dose increases were ≥ 2 weeks apart for patients taking a non–enzyme-inducing anti-seizure medication (non-EIASM) and weekly for those taking an EIASM. The primary endpoint was retention rate at 3, 6, 9, and 12 months. Secondary endpoints included seizure freedom (Maintenance Period) and safety. Exploratory endpoints included median percent reduction in seizure frequency (Maintenance Period) and cognition, assessed using EpiTrack
® (patients ≥ 6 years of age; baseline, and 3 and 12 months).
Results: In the Safety Analysis Set (SAS), 54 patients received perampanel monotherapy/first adjunctive therapy. Of those, 24 patients (FOS, n=17; FBTCS, n=2; GTCS, n=4) had a history of psychiatric and behavioral events, and were included in this analysis. The mean (SD) change from baseline in EpiTrack
® total score at 12 months (n=11) was -1.1 (3.14) (increase = improvement) (Table 1). Median percent reduction in seizure frequency/28 days during the entire Maintenance Period (last observation carried forward) was 73.2% (n=22). The incidence of any treatment-emergent adverse events (TEAEs) in this subgroup with a history of psychiatric and behavioral events was 95.8% (n=23/24 [41.7% reported psychiatric TEAEs]); in comparison, the incidence of TEAEs in the SAS was 88.9% [n=48/54]. Table 2 shows safety outcomes by treatment period.
Conclusions: Consistent with the overall ELEVATE Study results, this post hoc analysis showed that perampanel as monotherapy or first adjunctive therapy was generally safe and efficacious in patients with a history of psychiatric and behavioral events.
The change in EpiTrack
® score was consistent with that observed in the overall patient population from ELEVATE, suggesting that perampanel did not affect cognition in this subgroup.
Funding: Eisai Inc.