Combination AED Treatment With Clobazam in Patients With Lennox-Gastaut Syndrome: Post Hoc Analyses of the CONTAIN Study

Objective: To evaluate the efficacy of clobazam in combination with concomitant AEDs commonly used in patients with Lennox–Gastaut syndrome (LGS). Background: Clobazam is a 1,5-benzodiazepine indicated in the US as adjunctive treatment of seizures associated with LGS in patients ≥2 years of age. Design/Methods: This is a post hoc analysis of a randomized, double-blind, placebo-controlled study (NCT00518713) in which patients maintained on 1–3 concomitant AEDs received placebo or clobazam low (0.25 mg/kg), medium (0.5 mg/kg), or high (1.0 mg/kg) dosage. Median percent reduction and seizure response (≥50% reduction) in mean weekly drop seizures from baseline to maintenance (12-week treatment period) were evaluated for each clobazam dosage vs placebo, stratified by concomitant AED. Results: At baseline, most patients were receiving concomitant valproate (50.8%), lamotrigine (32.8%), levetiracetam (31.5%), or topiramate (30.3%). Valproate or topiramate-treated patients experienced significantly greater median reductions in average weekly drop seizures with adjunctive clobazam medium-dosage (71.2% valproate; 71.2% topiramate) and high-dosage (81.8% and 87.3%) versus placebo/valproate (31.6%, P P P P Conclusions: Patients in this post hoc analysis treated with medium- and high-dosage clobazam combined with valproate, lamotrigine, levetiracetam, or topiramate experienced improved seizure control, with no notable differences between non-randomized treatments. Clobazam reduced seizure rates when added to AEDs with different mechanisms of action in patients with LGS. Study Supported by: Lundbeck Disclosure: Dr. Chung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Chung has served as a consultant and speaker for Eisai Co., Ltd., Lundbeck LLC, Supernus Pharmaceuticals, UCB, and Upsher-Smith Laboratories. Dr. Chung has received research support from Dr. Chung has received research support from Eisai Co., Ltd., UCB Pharma, Lundbeck LLC, Upsher-Smith Laboratories, and SK Life Science, Inc. Dr. Gidal has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Gidal has served as a consultant and speaker for Eisai, Sunovion, UCB, and Lundbeck, and as a consultant for Upsher-Smith. Dr. Lemming has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with H. Lundbeck A/S employee. Dr. Karnik-Henry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck LLC employee. Dr. Hackler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck LLC employee. Dr. Karnik-Henry has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck LLC employee. Dr. Tworek has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck LLC employee. Dr. Sayeed has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Lundbeck LLC employee.