Abstracts

Rationale: In a Phase III study (CONTAIN), clobazam (CLB), a 1,5-benzodiazepine, significantly decreased the weekly frequency of drop and total seizures associated with Lennox-Gastaut Syndrome (LGS).¹ We conducted a post-hoc subanalysis to evaluate CLB s efficacy during the first 4 weeks of maintenance treatment vs. the last 4 weeks.Methods: The CONTAIN trial, a prospective, double-blind, placebo-controlled study, compared 3 oral dosages of CLB with placebo as adjunctive therapy for LGS. Patients (pts) 2 to 60 years of age with LGS (documented by both clinical and EEG 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. Primary endpoint was percentage (%) decrease in mean weekly frequency of drop seizures during maintenance vs. baseline phases for the modified intention-to-treat (mITT) population. The mITT analysis included all pts who had ?1 daily seizure measurement during the maintenance phase. We compared efficacy via average decreases in weekly drop seizure rates and other measures during the first 4 weeks of the maintenance phase with those during the last 4 weeks.Results: As previously reported¹, 301 pts were screened, 238 were randomized, 217 comprised the mITT population, and 177 completed the study. At baseline, pts mean age was 12.4 years, and 60.5% were male. Demographics and clinical characteristics were similar between groups. CLB statistically significantly decreased weekly frequencies of drop and total seizures associated with LGS.¹ Although different dropout rates for the treatment groups over time potentially confound these analyses, relative to placebo, the mean % reductions observed during the first 4 weeks of maintenance were maintained during the last 4 weeks of maintenance for all CLB groups. Statistically significant differences vs. placebo were observed for all pairwise comparisons except for the low-dosage group during the last 4 weeks of the maintenance period. Although the mean % reduction was numerically greater during the first 4 weeks vs. the last 4 weeks of maintenance in all groups, maintenance of efficacy in the CLB groups was greater than in the placebo group. The dosage-response pattern of results observed over time was generally similar between CLB groups for median % reductions, except that a greater median % decrease was observed for the placebo and low-dosage groups during the last 4 weeks vs. the first 4 weeks of the maintenance period.Conclusions: During CONTAIN, CLB low-, medium-, and high-dosage therapy led to statistically significant improvements in drop seizure rates vs. placebo during the first 4 weeks of a dosage maintenance period, and these improvements had generally been sustained during the final 4 weeks of the 12-week maintenance period for the medium- and high-dosage groups. References: ¹Conry J, et al. Epilepsia. 2010;Abstract #1.283.