Abstracts

Rationale: Clobazam, a 1,5-benzodiazepine, was FDA-approved in October 2011 for the treatment of seizures associated with LGS. With data from a Phase III, randomized controlled trial of clobazam in LGS (the CONTAIN trial¹), we conducted post-hoc analyses to evaluate the degree to which patients employed rescue medications during the maintenance period. Methods: CONTAIN,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 electroencephalographic 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 primary endpoint was the percentage decrease in mean weekly frequency of drop seizures during the maintenance vs. baseline phases for the modified intention-to-treat (mITT) population. The mITT analysis included all patients who had ≥1 daily seizure measurement during the maintenance phase. Patients were permitted rescue therapy of 1 rescue per day, with no more than a total of 4 days in 4 weeks (i.e., average of 1 rescue dosage per week). If more rescue treatments were required, the patient was considered a treatment failure, discontinued from the study, and tapered off study drug or enrolled in an open-label extension study. Treatment options included, but were not limited to, medications such as rectal diazepam and lorazepam. Clobazam was not used as a rescue therapy. Results: As previously reported,¹ 301 patients were screened, 238 were randomized, 217 comprised the mITT population (efficacy analyses), and 177 completed the study. The percentage of patients who received rescue medications at least once during the study was <20% in all treatment groups and lower in each clobazam group than in the placebo group (differences not statistically significant) (table) Conclusions: Rescue medications were used infrequently during the maintenance period of CONTAIN. In addition, there were no clinically important or statistically significant differences between treatment groups in the percentage of patients who employed rescue medications on multiple occasions. However, there was a trend toward less frequent use of rescue medications in the low-, medium- and high-dosage clobazam groups. References: ¹Ng YT, et al. Neurology. 2011;77:1473-81.