Abstracts

Rationale: Patients with Lennox-Gastaut syndrome (LGS) differ by disease severity. Vagal nerve stimulation (VNS) is one of the treatment options for LGS patients. Clobazam, a 1,5-benzodiazepine, was approved in October 2011 for the treatment of seizures associated with LGS. We conducted a post-hoc subgroup analysis of the pivotal Phase III trial, CONTAIN,¹ to evaluate responses to clobazam therapy for patients who were undergoing VNS during the trial vs. those who were not. Methods: The CONTAIN trial,¹ a prospective, double-blind, placebo-controlled study, compared 3 oral dosages of clobazam with placebo as adjunctive therapy for LGS. Patients 2 to 60 years of age with LGS (documented by both clinical and EEG criteria) enrolled. 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), up to a maximum daily dosage of 40 mg. Treatment included a 3-week titration phase, followed by a 12-week maintenance phase. The mITT analysis included all patients who had ≥1 daily seizure measurement during the maintenance phase. Patients were grouped based on whether they were receiving or not receiving VNS treatment during the study. All clobazam dosage groups (low-, medium-, and high-dosage) were combined in these analyses. Results: Both groups experienced statistically significant mean percentage decreases in average weekly seizures for both drop and total seizures (drop plus non-drop) vs. the placebo group (table). More than 50% of patients demonstrated ≥50% decreases in average weekly seizure frequencies in both groups, for both drop and total seizures, and >10% of patients achieved drop-seizure-freedom in both groups. Conclusions: Clobazam therapy provided similar efficacy in improving rates of drop and non-drop seizures for patients with LGS, regardless of whether they were receiving VNS treatment or not. These results suggest that clobazam is efficacious not only for less severe LGS patients, but also for more refractory patients with LGS (as those receiving VNS therapy tend to be). References: ¹Ng YT, et al. Neurology. 2011;77:1473-81.