Journal
EPILEPSIA
Volume 63, Issue 11, Pages 2994-3004Publisher
WILEY
DOI: 10.1111/epi.17411
Keywords
clinical trials; epilepsy; genetic generalized epilepsy; perampanel; primary generalized tonic-clonic seizures; time to event
Categories
Funding
- National Institutes of Health (NIH) [R25NS089450, U24NS107158]
- American Epilepsy Society
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The study evaluated the exploratory time to exceed pre-randomization seizure count (T-PSC) in participants with primary generalized tonic-clonic seizures. The results showed that perampanel demonstrated effectiveness in a shorter duration of monitoring. Therefore, T-PSC may be considered as a viable alternative trial endpoint.
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.
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