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 In addition, CLB was consistently efficacious in decreasing weekly rates of drop seizures from baseline to the maintenance phase compared with placebo for all age groups and dosages, with the exception of patients 12 to <17 years of age in the low-dosage group.² This exception was likely a result of low sample sizes and was not considered meaningful. We conducted post-hoc analyses of CONTAIN s open-label extension (OLE) study to determine if these results were sustained over the long term.Methods: In an OLE (OV-1004),³ LGS patients who had completed 1 of 2 RCTs OV-1002 (Phase II⁴) or OV-1012 (Phase III/the CONTAIN trial¹) received open-label CLB. Most patients initially received 0.5 mg/kg/day ( 40 mg/day). Dosages were then adjusted based on clinical response (efficacy and tolerability), up to 2.0 mg/kg/day (80 mg/day). Visits were at Day 1, Week 1, Months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter (through Year 6). During the week preceding each visit, parents/caregivers maintained seizure diaries. Patients outside the United States did not continue in the study beyond 24 months, per protocol, resulting in much lower patient numbers for Year 3 and beyond. In this post-hoc subanalysis, we evaluated results from baseline (first day patients received CLB) to the specified time points in the open-label extension for patients 2 to <12 years of age; patients 12 to 16 years; and patients >16 years.Results: As previously reported, 267 of 306 patients from OV-1002 (61 of 68) or OV-1012 (206 of 238) entered the OLE. As of March 23, 2012, 188 (70.4%) had completed the study. 251 patients had received CLB for 6 months, 229 for 1 year, 210 for 2 years, 121 for 3 years, 54 for 4 years, 44 for 5 years, and 11 for 6 years. At entry, patients mean age was 11.3 years, and their mean time since diagnosis was 6.4 years.⁵ Within each category, patients in all dosage groups continued to achieve greater mean and median percentage reductions in average weekly rates of drop seizures from baseline through Year 3 (table). Of note, persistence of efficacy was present in the 12 to 16 years age group.Conclusions: As in the CONTAIN trial, open-label CLB was consistently efficacious in decreasing weekly rates of drop seizures from baseline for all age groups. Seizure improvement in adult patients with LGS was consistent with results achieved by younger patients. ¹Ng YT, et al. Neurology. 2011;77:1473 81. ²Mitchell W, et al. Epilepsy Curr. 2012;12(1 Suppl 1):Abstract #B.04. ³Ng Y-T, et al. Epilepsy Behav. 2012;25:687 94. ⁴Conry JA, et al. Epilepsia. 2009;50:1158 66. ⁵Ng Y-T, et al. Late-Breaking Abstract #1.363, AES 2012.