Abstracts

Rationale: People with epilepsy have increased risk of falls and injury, with some incidents considered seizure-related and others a result of adverse events (AEs) from antiepileptic drugs (AEDs).1,2 In 3 Phase III double-blind (DB) studies of perampanel (PER) in patients with partial seizures, the AE of falls was considered a common treatment-emergent adverse event (TEAE), with incidence rates being dose dependent and higher with PER (5.1%) vs placebo (PBO;3.4%). However, all falls were captured, whether or not they were the result of a seizure. In Study 332, a Phase III DB study evaluating the efficacy and safety of PER in patients with PGTCS, a systematic review of reported falls was conducted, and falls were evaluated to establish whether each event was related to a seizure; subjects whose falls resulted from seizures were not included in this analysis.Methods: Subjects ≥12yrs old had a clinical diagnosis of PGTCS and were taking 1-3 concomitant AEDs. Following a baseline period (4 or 8 wks), subjects were randomized into PER or PBO groups for the DB Treatment Phase (Titration, 4 wks; Maintenance, 13 wks), with a maximum dose of 8mg PER. Falls were summarized by Prerandomization Phase and Follow-up Period and by actual dose at onset for the Titration and Maintenance Periods. A TEAE was defined as an AE that emerged, reemerged or worsened in severity during treatment and occurred up to 30 days after the last dose.Results: Of the 163 subjects in the Safety Analysis Set (PER, N=81; PBO, N=82), 2 (2.5%) PER- and 1 (1.2%) PBO-treated subject had TEAEs related to falls that were not part of a seizure. Exposure-adjusted rates were 0.0169 and 0.0032 per subject-month of exposure in PER and PBO subjects, respectively (Table 1). The 2 PER-treated subjects had a total of 5 falls during treatment; 1 subject had 1 fall during the Maintenance Period on Day 113 (dose 6mg); and 1 subject (who also had 3 falls during prerandomization) had 1 fall during the Titration Period on Day 8 (dose 4mg), 1 on Day 29 (dose 8mg), and 1 on Day 46 (dose 8mg) during the Maintenance Period, and 1 on Day 117 (23 d after last dose). Each of these 5 fall events was considered not related to study drug and did not lead to discontinuation for either PER-treated subject. The PBO-treated subject had 1 fall during the Maintenance Period (Day 75) that resulted in superficial bruising and hospitalization; the fall was considered a serious TEAE.Conclusions: In Study 332, a systematic review of reported falls was conducted to capture falls not associated with seizures. The incidence of falls not related to seizures in subjects with PGTCS was 2.5% in PER subjects vs 1.2% in PBO subjects, , and these falls did not lead to discontinuation. In the 3 Phase III studies in patients with partial seizures, in which all falls were captured, there was an increased risk of falls (with or without concurrent seizures), some of which led to discontinuation of PER. Patients with epilepsy should be monitored due to the common risk of falls and injury. 1Mattson.EpilepsyBehav 2004;5:S36. 2ShiekAhmad.Neurology 2012;79:145. Support: Eisai Inc.