Abstracts

Rationale: Antiepileptic drug (AED) treatment is associated with adverse events (AEs) that may affect the CNS, behavior and other body systems.1 In 3 Phase III double-blind (DB) perampanel (PER) studies in subjects with partial seizures, there were no clinically important changes in mean lab values and no notable differences between PER and placebo (PBO) groups in hepatobiliary lab data. Here we evaluate lab tests and treatment-emergent AEs (TEAEs) related to these tests, as well as cardiac-, hepatic- and renal-related TEAEs in subjects enrolled in the primary generalized tonic-clonic seizure (PGTCS) Phase III study.Methods: Subjects aged ≥12yrs had clinical diagnosis of PGTCS and were taking 1-3 concomitant AEDs. Following baseline (4 or 8wks), subjects were randomized to PER or PBO for DB Treatment Phase [Titration(4wks); Maintenance(13wks)] with 8mg maximum dose. Clinical lab tests performed at certain study visits were analyzed for the safety population (treated subjects with ≥1 postbaseline safety assessment; N=81:PER, N=82:PBO). Abnormal lab test results and incidence of TEAEs related to cardiac, drug-related hepatic disorder abnormalities and renal/urinary disorders were evaluated.Results: Mean values for hematology and chemistry parameters for the total population were within standard laboratory normal ranges at baseline and end of treatment. Most subjects with normal values at baseline had postbaseline values within normal range for all lab parameters. ≤4% of subjects had abnormal postbaseline values that met the criteria to be considered treatment-emergent markedly abnormal values (Table 1). Additional analysis of liver function tests showed no PER- or PBO-treated subject met criteria for drug-induced liver injury (Hy’s Law). Results for cholesterol and triglycerides (fasting or nonfasting) showed: (i) 1 adult and 1 adolescent PER-treated subject had increase in cholesterol ≥50 or ≥40 mg/dL, respectively; and (ii) among adult subjects, 38.6% PER vs. 16.2% PBO subjects had increase in triglyceride values ≥50 mg/dL (increase ≥100 mg/dL was 11.4% and 2.7%, respectively). A total of 12(14.8%) PER- and 8(9.8%) PBO-treated subjects had TEAEs related to lab abnormalities (Table 2). Incidence of TEAEs associated with drug-related hepatic disorders, potential cardiac abnormalities and renal/urinary disorder was low (≤2.5% subjects for both treatment groups in each category).Conclusions: There were no clinically relevant changes in total population mean lab test results for PER-treated subjects from baseline to end of treatment; the only potentially clinically important change with PER concerned triglycerides (fasting or nonfasting). Safety results from lab tests and investigator-reported TEAEs of 8mg PER in subjects with PGTCS were consistent with those reported in Phase III studies of partial seizures. Data from these studies do not suggest a need for routine clinical lab monitoring nor is it required for patients treated with PER. 1Cramer.ExpRevNeurother.2010;10:885 Support: Eisai Inc.