Objective:

To report a post hoc analysis of efficacy and safety data from Phase III Study 338 (NCT02834793) by treatment period, assessing early and sustained treatment effect of adjunctive perampanel.

Background:

Study 338 evaluated long-term effects of perampanel in patients with uncontrolled seizures associated with Lennox-Gastaut syndrome (LGS).

Design/Methods:

Patients with LGS receiving 1–4 concomitant anti‑seizure medications and an average of ≥2 drop seizures/week during baseline were enrolled. The study consisted of a randomized, placebo-controlled Core Study (6-week Titration, 12-week Maintenance) and Extension Phase (6-week Conversion, 46-week Maintenance). During the Extension Phase, all patients received perampanel treatment. The primary endpoint was change from baseline in drop seizure frequency/28 days during the Core Study. Secondary endpoints included 50% responder rates and safety outcomes. Outcomes were assessed in prior perampanel vs prior placebo groups during Titration (Core Study Titration vs Extension Phase Conversion), Maintenance (Core Study Maintenance vs initial 12-week Extension Phase Maintenance), and Long-Term Treatment (52-week Extension Phase vs remaining 34-week Extension Phase Maintenance) Periods.

Results:

In the Extension Phase, 58 patients received perampanel (prior perampanel, n=26; prior placebo, n=32). During Titration, Maintenance, and Long-Term Treatment Periods, the median percent reduction in drop seizures/28 days were 33.4%, 42.1%, and 34.3%, respectively; similarly, the 50% responder rates were 29.3%, 37.9%, and 32.8%, respectively. Treatment-emergent adverse events (TEAEs) occurred in >60% of patients throughout the study; the incidence of treatment-related TEAEs peaked during the Titration Period and subsequently declined over time. The most common TEAEs during each treatment period were somnolence (12.1%; Titration), upper respiratory tract infection (9.3%; Maintenance), and nasopharyngitis and pyrexia (9.8% each; Long-Term Treatment).

Conclusions:

Adjunctive perampanel demonstrated early-onset efficacy that was sustained long term (≥46 weeks) and was well tolerated in patients with LGS.