Abstracts

Rationale: The efficacy of antiepileptic drugs (AEDs) may be influenced by the background characteristics of each patient. Perampanel, a selective, non-competitive AMPA receptor antagonist, is a newer AED with a novel mode of action, therefore its target patient population has not been fully elucidated. A randomized, double-blind, placebo-controlled Phase III study (study 335; NCT01618695) involving patients with refractory partial-onset seizures from the Asia-Pacific region showed that perampanel 8 and 12 mg/day had a statistically significant effect on change in seizure frequency, but 4 mg/day failed to show any statistically significant effect. Using a multivariate analysis, we investigated factors that might have influenced the efficacy of perampanel in this patient population. Methods: Our database was the intent-to-treat analysis set (n=704). Treatment groups were placebo and once-daily perampanel 4 mg, 8 mg, or 12 mg; patients were randomized in a 1:1:1:1 ratio. Selected variables for the multivariate analysis were: gender; body mass index; combined usage of an inducer AED; seizure frequency during the baseline period; number of concomitant AEDs; age at onset; duration of disease; use of central-nervous-system (CNS) drugs (anxiolytics, antipsychotics, antidepressants etc); use of vagus nerve stimulation; etiology (hippocampal sclerosis, tuberous sclerosis, other intracranial pathology); mental retardation; classification of epilepsy; and estimated epileptogenic zone. Variables influencing change in seizure frequency were selected using a stepwise method (significance level, 15%). Change in seizure frequency showed a non-normal distribution, therefore logarithmic transformation of the data was conducted; our analysis assumed logarithmic normal distribution. Results: Combined use of inducer (P < 0.0001), age at onset (P=0.010), use of CNS drugs (P=0.029), and number of concomitant AEDs (P=0.148) were selected as factors influencing change in seizure frequency. Analysis of interaction with treatment groups revealed age at onset had the strongest impact (P=0.118). A model adjusted for combined use of inducer, use of CNS drugs, and number of concomitant AEDs suggested that younger age at onset influenced the poorer efficacy of perampanel 4 mg/day. On the other hand, response to perampanel 8 and 12 mg/day was not influenced by age at onset. Conclusions: Multivariate analysis revealed that combined use of inducer, use of CNS drugs, and number of concomitant AEDs influenced the efficacy of perampanel in patients with partial-onset seizures. Younger age at onset of epilepsy influenced the poorer efficacy of perampanel 4 mg/day, but this was not the case for perampanel 8 and 12 mg/day. Funding: Eisai Co., Ltd