Effects of Concomitant Lamotrigine or Valproate Therapy on Clobazam for Lennox-Gastaut Syndrome: Subanalyses of the CONTAIN Trial (P06.120)

Abstract

Objective: We conducted a subanalysis of a Phase III trial to evaluate clobazam9s efficacy with concomitant lamotrigine or valproate therapy. Background In CONTAIN,1 clobazam, a 1,5-benzodiazepine, significantly decreased weekly frequency of drop and total seizures associated with LGS.1 Design/Methods: CONTAIN, a double-blind, placebo-controlled study, compared 3 dosages of clobazam with placebo as adjunctive therapy for LGS. Patients 2–60 years of age with LGS enrolled.1 In this post-hoc subanalysis, we evaluated results from baseline to 12-week maintenance phase for patients who also received lamotrigine or valproate therapy. We also used a popPK model to assess interactions of clobazam and its active metabolite (N-CLB) with lamotrigine and valproate. Results: As reported1, 301 patients were screened, 238 were randomized, 217 comprised the mITT population, and 177 completed the study. At baseline, patients9 mean age was 12.4 years, and 60.5% were male. Demographics/clinical characteristics were similar between groups. Clobazam significantly decreased weekly frequencies of drop and total seizures associated with LGS.1 For 72 patients receiving concomitant lamotrigine, all clobazam groups achieved a greater mean percentage decrease in average weekly rate of drop seizures from baseline to maintenance period vs. placebo. For 113 patients receiving concomitant valproate, all dosage groups had a greater mean reduction in average weekly rate of drop attacks vs. placebo. Efficacy was dosage-dependent for patients receiving clobazam and either concomitant lamotrigine or valproate, consistent with overall results. Kruskal-Wallis analysis indicated no significant effects between clobazam or N-CLB and lamotrigine or valproate concentrations. Conclusions: In CONTAIN, clobazam was consistently efficacious in decreasing weekly rates of drop seizures from baseline to maintenance phase vs. placebo for patients receiving either concomitant lamotrigine or valproate. Efficacy was dosage-dependent, consistent with overall results. No dosage adjustment of lamotrigine or valproate appears to be required when coadministered with clobazam. 1Ng YT, et al. Neurology. 2011;77:1473–81. Supported by: Lundbeck Inc. Disclosure: Dr. Renfroe has received research support from Lundbeck Inc. Dr. Conry has received personal compensation for activities with Lundbeck Research USA, Inc., and ID&A. Dr. Conry has received personal compensation for activities with Lundbeck Research USA, Inc., Marinus, Eisai Inc., King, and Abbott Laboratories, Inc. Dr. Ng has received personal compensation for activities with UCB Pharma, Cyberonics, Inc., and Lundbeck Research USA, Inc. Dr. Ng has received research support from UCB Pharma. Dr. Drummond has received personal compensation for activities with Lundbeck, Inc. as an employee. Dr. Owen has received personal compensation for activities with Lundbeck Research USA, Inc.