Abstracts

Rationale:
In the US, perampanel is approved for partial-onset seizures (adjunctive and monotherapy) in patients aged ≥ 4 years, and adjunctive treatment of primary generalized tonic-clonic (PGTC) seizures in patients aged ≥ 12 years. Adjunctive perampanel 8 mg/day has previously shown efficacy and safety for PGTC seizures in the randomized, double-blind, placebo-controlled Phase III Study 332 (NCT01393743) in patients aged ≥ 12 years. This post hoc analysis further evaluates the efficacy of adjunctive perampanel for PGTC seizures by assessing the time to first seizure following perampanel administration.
Method:
Patients (aged ≥ 12 years) with idiopathic generalized epilepsy and uncontrolled PGTC seizures, despite receiving treatment with 1–3 concomitant anti-seizure medications, were randomized to receive once-daily placebo or adjunctive perampanel 8 mg/day across a 17-week Double-blind Treatment Period (4-week Titration; 13-week Maintenance). The primary efficacy endpoint was median percent change in PGTC seizure frequency per 28 days from baseline; median percent change in the frequency of all seizures was also assessed. Time to first seizure onset from Day 1 of placebo or perampanel administration was assessed as a post hoc analysis in the Full Analysis Set using the Kaplan–Meier method.
Results:
The Full Analysis Set included 162 patients (placebo, n=81; perampanel, n=81). Median percent reductions in PGTC seizure frequency per 28 days were 38.4% with placebo vs 76.5% with perampanel 8 mg/day (P< 0.0001), and for all seizures were 22.9% vs 43.4% (P=0.0018), respectively. Compared with placebo, adjunctive perampanel 8 mg/day was associated with a longer time to first PGTC seizure (Figure 1A) and all seizures (Figure 1B). Mean (median [range]) time to first PGTC seizure was 27.0 (12 [1, 126]) for placebo and 45.3 (19 [1, 127]) for perampanel 8 mg/day, and for all seizures was 12.5 (4 [1, 126]) and 31.2 (5 [1, 127]), respectively.