Abstracts

Rationale: In Phase II (OV-1002¹) and Phase III (CONTAIN²) studies, clobazam, a 1,5-benzodiazepine, significantly decreased the weekly frequencies of drop and total seizures associated with Lennox-Gastaut syndrome (LGS). Adverse events were as expected, given what is known about clobazam from extensive previous clinical development efforts.² Following an earlier analysis indicating that clobazam was generally consistently efficacious in treating LGS across all age groups,³ we conducted a pooled analysis of both trials to determine if safety events varied by age. Methods: In the Phase II trial,¹ LGS patients, following a 4-week baseline phase, were randomized to 1 of 2 dosages of clobazam (0.25 and 1.0 mg/kg/day). Treatment included a 3-week titration period, followed by a 4-week maintenance period. The Phase III CONTAIN trial² compared 3 oral dosages of clobazam with placebo as adjunctive therapy for LGS. Following a 4-week baseline phase, patients who had ≥2 drop seizures per week were randomized to placebo or 1 of 3 dosages of clobazam (0.25, 0.5, and 1.0 mg/kg/day). Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. The safety population included all patients who received ≥1 dose of study drug or placebo. We evaluated safety results from the baseline period to the maintenance phase in each trial for patients ≥2 to <12 years of age; patients ≥12 to <16 years; and patients ≥16 years. Results: As previously reported,² 301 patients were screened, 238 were randomized, 217 comprised the mITT population, and 177 completed the study. For overall incidence of serious adverse events, no notable differences between age groups were observed (table). Incidences of low hemoglobin and hematocrit concentrations were lower for older vs. younger patients. In addition, the percentages of patients with ≥1 elevated alkaline phosphatase concentration were notably different between groups. None of these differences were considered clinically important by the study investigators. Conclusions: From pooled Phase II/III results for clobazam in LGS, we observed no clinically important differences in treatment-emergent adverse events and laboratory values when patients were categorized by age. References: ¹Conry JA, et al. Epilepsia. 2009;50:1158-66. ²Ng YT, et al. Neurology. 2011;77:1473-81. ³Mitchell W, et al. Epilepsia. 2011;Abstract #B.04.