BALTIMORE — Patients with Lennox-Gestaut Syndrome who were treated with clobazam experienced fewer atonic seizures and seizure-related injuries compared with those treated with placebo, phase-3 study findings from the CONTAIN trial indicate.
Weekly frequency of drop seizures decreased a median 85% among patients in the high-dose group (1 mg/kg/day; P<0.001) and a median 58.5% among those in the medium-dose group (0.5 mg/kg/day; ≤0.05) compared with placebo, Jouko Isojärvi, MD, PhD, and colleagues, reported at the American Neurological Association 2014 Annual Meeting.
The 15-week CONTAIN trial completers analysis involved 217 patients, who were randomly assigned to one of three clobazam (Onfi, Lundbeck) dosages — 0.25, 0.5 or 1.0 mg/kg/day — and underwent a three-week titration phase followed by a 12-week maintenance phase. Overall, 177 patients completed the 15-week analysis.
Patients in the high-dose group experienced a significant does-related increase in the proportion of those who experienced at least a 50% reduction in atonic seizures compared with placebo (16% vs. 12%, unadjusted P<0.001), as did those in the medium-dose group (38% vs. 12%; unadjusted ≤0.05).
Findings were similar for the proportion of patients who experienced at least a 75% reduction in drop seizures (high-dose, 78% vs. 37%, unadjusted P<0.001; medium-dose, 62% vs. 37%, unadjusted ≤0.05), the researchers reported.
In a separate analysis to assess seizure-related injuries in the same group of patients, those who received any dose of clobazam (n=179) experienced fewer seizure-related injuries as measured by MedDRA preferred terms compared with the placebo group (n=59) — 5% vs. 14% (≤0.05).
“This indicates that the reduction in drop-seizure frequency provides a clinically meaningful benefit, a reduced likelihood of experiencing seizure-related injuries,” Isojärvi and colleagues reported.
Clobazam was just as safe and effective among patients previously treated with benzodiazepines, with similar percentage decreases in the average weekly rate of drop seizures in a third subanalysis of the same patient group, the researchers noted.
The most common treatment-emergent adverse events included somnolence, lethargy, drooling, upper respiratory tract infection, and pyrexia.
- Isojärvi J et al. #S208. “Efficacy and Safety of Clobazam in LGS: Completers Analysis of the 15-Week, Phase III CONTAIN Trial.”
- Isojärvi J et al. #S209. “Clobazam Response in Patients with Previous Benzodiazepine Use: Subanalysis of the Phase III Trial in LGS.”
- Isojärvi J et al. #S210. “Patients Treated with Clobazam Experienced Fewer Seizure-Related Injuries Than Placebo Patients During the Phase III CONTAIN Trial in LGS.” All presented at: American Neurological Association 2014 Annual Meeting. October 12-14, 2014; Baltimore.
Disclosures: The study was financially supported by Lundbeck LLC. Isojärvi and Lee are full-time Lundbeck employees and Sperling is a Lundbeck study investigator.