Abstracts

Clobazam (CLB) has been approved for the treatment of anxiety and/or the adjunctive treatment of epilepsy in over 100 other countries. Anticonvulsant effects of CLB was first reported on by Gastaut in 1978. CLB is the only 1,5 benzodiazepine used in the treatment of epilepsy and was developed to decrease the side effects of 1,4-benzodiazepines while maintaining efficacy. This study evaluates the safety and efficacy of CLB as adjunctive therapy in subjects with Lennox-Gastaut Syndrome (LGS)., Subjects from 2-30 years of age with LGS were enrolled in a randomized, double-blind, dose-range finding study. The study consists of a 4-week baseline, a 3-week titration and a 4-week maintenance period. Subjects not continuing into the long term open-label study have up to a 3-week taper period. Subjects must be on stable doses of 1-3 AEDs which may include ketogenic diet and VNS. Subjects with [ge]2 drop seizures per week are randomized to low dose (target 0.25 mg/kg/day) or high dose (target 1.0 mg/kg/day) with maximum doses of 10 or 40 mg/day, respectively. The primary efficacy variable is a reduction in drop seizures. Safety of CLB is evaluated by lab assessments, electrocardiogram, vital signs, physical and neurological exams and adverse event (AE) assessments., Of the 76 subjects enrolled to date, 49 (64%) have been randomized and have received study drug. Of the randomized subjects, demographic data is available in 51%: 72% male, 28% female; 28% [lt]5 years of age, 48% 5[ndash]10 years of age and 24% [gt]10 year of age. AEs resulted in 5 premature discontinuations due to drowsiness, hypothermia, increase in seizures, increased behavioral problems and chorea. AEs were reported by 32% of the subjects with the majority mild in severity (66%); 24% were considered not related, 21% unlikely, 24% possibly and 28% probably related to study drug by the investigator; relationship for 1 event was not reported (ear infection). No AEs were considered definitely related. The most frequently reported AEs by [ge]2 subjects were constipation (2), ear infection (2), sedation (2), somnolence (2) and increased seizures (3). There were no reports of drooling. One subject reported irritability and 1 reported dysphoria, both mild in severity and considered possibly related. A total of 6 serious adverse events (SAEs) have been reported. Of the SAEs, 4 were treatment-emergent; 3 (constipation, viral infection and sleep apnea syndrome) were considered not related and 1 (respiratory distress) was considered unlikely related., Of the 49 subjects randomized to date, no SAEs have been attributed to clobazam. Clobazam is a promising agent for the treatment of LGS., (Supported by Ovation Pharmaceuticals.)