Abstracts

Rationale: Somnolence and sedation are common adverse events related to treatment with benzodiazepines. It has been hypothesized that treatment with clobazam, a 1,5-benzodiazepine, may be less frequently associated with these types of adverse events than treatment with 1,4- benzodiazepines. This post-hoc subanalysis of the Phase III CONTAIN trial,¹ evaluated the incidence and time to resolution of somnolence and sedation for patients with LGS. Methods: The CONTAIN trial,¹ a prospective, double-blind, placebo-controlled study, compared 3 oral dosages of clobazam with placebo as adjunctive therapy for LGS. Patients 2 to 60 years of age with LGS (documented by both clinical and electroencephalographic criteria) enrolled. Following a 4-week baseline phase, patients who had ≥2 drop seizures per week were randomized to placebo or 1 of 3 dosages of clobazam (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. The mITT analysis included all patients who had ≥1 daily seizure measurement during the maintenance phase. Incidence, time to onset, duration, and time to resolution of somnolence-related AEs (defined as somnolence and sedation) were analyzed for patients treated with placebo, or low-, medium-, or high-dosage clobazam. Results: The incidence of somnolence and/or sedation was greater for patients treated with clobazam (26%) than patients treated with placebo (15%). Further, the incidence increased with greater dosages of clobazam (low-dosage, 17%; medium-dosage, 27%; and high-dosage, 32%). For most patients, onset of these events was within the first 3 weeks of treatment (i.e., during titration). The majority of these events resolved (placebo, 73%; low-dosage, 82%; medium-dosage, 63%; and high-dosage, 83%). The median duration of these somnolence-related adverse events was within 2-3 weeks for all clobazam treatment groups. Conclusions: Somnolence and sedation were relatively common adverse events observed during clobazam treatment in CONTAIN, and were dosage-related. However, most of these events were transient and resolved within a few weeks. References: ¹Ng YT, et al. Neurology. 2011;77:1473-81.