Objective:

We evaluated if the Time to Pre-randomization monthly Seizure Count (T-PSC) design could replicate tolerability and safety conclusions of three placebo-controlled trials of perampanel for focal-onset seizures.

Background:

In traditionally designed randomized clinical trials of antiseizure medications, participants take a blinded treatment for a pre-specified number of weeks, irrespective of continued seizures. The alternative T-PSC design allows participants to end the blinded treatment after an individually pre-specified number of seizures, which shortens exposure to placebo and ineffective treatment.

Design/Methods:

We retrospectively applied the T-PSC design to analyze Treatment Emergent Adverse Events (TEAEs) from 3 blinded, placebo-controlled trials of perampanel for focal-onset seizures (NCT00699972, NCT00699582, NCT00700310). We evaluated the incidences of TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs that prompted medication adjustment to those observed during the full-length trial.

Results:

Of the 1,480 participants in the 3 trials, 1,093 experienced any TEAE, of which 1,006 (92%) had onset prior to T-PSC. When evaluating the differences in each type of TEAE for each dose of perampanel to placebo within each trial, there was no consistent pattern of under- or over-estimation. Across the 3 studies, 23 of 79 (29%) serious TEAEs, most requiring hospitalization, occurred after T-PSC.

Conclusions:

Almost all TEAEs occurred before T-PSC. Similar conclusions regarding the tolerability and safety of perampanel would have been reached if the T-PSC design had been used. This suggests that the T-PSC design may potentially benefit participants by allowing earlier change from an ineffective treatment to an alternate treatment, which could reduce the risk of serious consequences of ineffective treatment, such as hospitalization.