Time to exceed pre‐randomization monthly seizure count for perampanel in participants with primary generalized tonic–clonic seizures: A potential clinical end point

OBJECTIVE: To evaluate the exploratory time to exceed pre‐randomization seizure count (T‐PSC) in the determination of efficacy of adjunctive perampanel in participants with primary generalized tonic–clonic (PGTC) seizures in generalized‐onset epilepsy. METHODS: In this multicenter, double‐blind study (ClinicalTrials.gov identifier: NCT01393743), participants ≥12 years of age with treatment‐resistant idiopathic generalized epilepsy were randomized to receive placebo or adjunctive perampanel (≤8 mg/day) across a 17‐week double‐blind treatment phase (4‐week titration; 13‐week maintenance). We evaluated the pre‐planned exploratory end point of the T‐PSC using a Kaplan–Meier analysis. We also re‐evaluated the correspondence of the primary end points of median percent seizure frequency change (MPC) and 50% responder rate (50RR) calculated at T‐PSC and at the end of the trial. RESULTS: The exploratory end point of median T‐PSC on placebo was 43 days and >120 days on perampanel (log‐rank p < .001). The primary end points calculated at T‐PSC did not differ significantly from the end points at the end of the trial (MPC −31% vs −42% at T‐PSC; 50RR 32% vs 51% at T‐PSC). After T‐PSC was reached, participants had a median (interquartile range) of 5 (3–13) additional seizures on placebo and 5 (2–10) on perampanel. SIGNIFICANCE: The exploratory end point of T‐PSC demonstrated the effectiveness of perampanel despite a shorter duration of monitoring. The seizures that occurred after T‐PSC did not influence the conclusions of the trial; therefore, T‐PSC may be a viable alternative to traditional trial end points that reduces the risk to participants.