Abstracts

Rationale: The Phase III CONTAIN study demonstrated the efficacy and safety of clobazam (CLB), a 1,5-benzodiazepine, in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS).¹ Drop seizures are especially problematic because of their potential for serious injury. We conducted a post-hoc analysis to determine the incidence of seizure-related injuries for patients (pts) receiving CLB therapy vs. placebo during CONTAIN.Methods: CONTAIN,¹ a placebo-controlled study, compared 3 oral dosages of CLB with placebo as adjunctive therapy for LGS. Pts 2 to 60 years of age with LGS (documented by both clinical and electroencephalographic criteria) enrolled. Following a 4-week baseline phase, pts who had 2 drop seizures per week were randomized to placebo or 1 of 3 dosages of CLB (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 pts who had 1 daily seizure measurement during the maintenance phase. We conducted a medical review of treatment-emergent, seizure-related injuries based on Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and other information (i.e., alternative etiologies) from all adverse event listings in CONTAIN. Results: As previously reported,¹ 301 pts were screened, 238 were randomized, 217 comprised the mITT population (efficacy analyses), and 177 completed the study. Pts receiving CLB experienced fewer seizure injuries than those receiving placebo (table). Dosage did not appear to affect the rate of injuries in the 3 CLB groups. Most of the injuries were not serious, and most resolved.Conclusions: In this post-hoc analysis of the CONTAIN study, the incidence of seizure-related injuries was lower for CLB-treated pts than for those in the placebo group. This indicates that the reduction in drop-seizure frequency achieved with CLB provides a clinically meaningful benefit, a reduced likelihood of experiencing seizure-related injuries. ¹Ng YT, et al. Neurology. 2011;77:1473 81.