Perampanel in the treatment of partial seizures: Time to onset and duration of most common adverse events from pooled Phase III and extension studies.

Perampanel (PER) is a novel noncompetitive AMPA-receptor antagonist approved in over 40 countries for treatment of partial seizures. The safety and tolerability of PER have been well-documented in three double-blind, randomized, placebo (PBO)-controlled Phase III studies and an open-label extension (OLE). This post hoc analysis evaluated the occurrence and characteristics of the most common treatment-emergent adverse events (TEAEs) associated with PER. Results from the Phase III studies were pooled; post hoc analyses on the double-blind phase and up to 1 year of the OLE were performed on the four most common TEAEs for which incidence was higher for PER than PBO. The four most common TEAEs were dizziness, somnolence, fatigue, and irritability. For most subjects in the Phase III double-blind studies, these TEAEs were observed during 6-week titration and were mild or moderate in severity. For severe AEs, no dose-response relationship was observed. Patients in the PBO group during Phase III (who therefore received their first PER treatment during OLE) experienced these TEAEs with incidence and timing similar to that of PER-treated patients in Phase III. The first onset of these TEAEs occurred during the early weeks of PER conversion in the OLE. After 6months and up to 1 year of PER treatment, low to no incidence of the first onset of the four TEAEs was observed. Post hoc analyses of data from pooled Phase III studies provide greater insight into occurrence/duration of TEAEs. Phase III double-blind and OLE data showed that dizziness, somnolence, fatigue, and irritability were the most common TEAEs reported by patients taking PER. Additionally, these results suggest consistency between studies in patient responses to onset of these TEAEs. Although concomitant antiepileptic drugs (AEDs) might be predicted to affect development of TEAEs in patients taking PER, an effect was not observed in this analysis. The low incidence of TEAEs in these studies provides additional support for long-term PER treatment.

RCT Entities:   Population Interventions Outcomes