Treatment with clobazam reduces the likelihood of seizure-related injuries in Lennox-Gastaut syndrome, in which drop seizures are common and problematic, data indicate.
The results of the post hoc analysis, published in Epilepsia, indicate a clinically meaningful benefit for patients taking the antiepileptic drug.
Noting that standard end points used in clinical trials to evaluate drug efficacy often fail to indicate whether or not a measure will have clinical meaning, researchers led by Michael R. Sperling, MD, of Thomas Jefferson University in Philadelphia, PA explored the rate of seizure-related injuries in patients with Lennox-Gastaut syndrome who were treated with clobazam.
For the post hoc analysis, the researchers reviewed all adverse event listings recorded during the OV-1012 phase 3, randomized, placebo-controlled study. Ultimately, 177 patients completed the study.
Overall, patients who received clobazam experienced significantly fewer seizure-related injuries than those taking placebo (P<0.05). The rates of seizure-related injuries were statistically significantly lower in the media dosage group (target of 0.5 mg/kg/day [maximum 20 mg/day]; 4.8%, P<0.001) and high dosage group (target of 1.0 mg/kg/day [maximum 40 mg/day]; 10.2%, P<0.03) compared to the placebo group (27.1%). Findings in the low-dosage group (target of 0.25 mg/kg/day [maximum 10 mg/day]) were not statistically significant.
Notably, 32 patients total experienced seizure-related adverse events, of which nearly 95% were of mild to moderate intensity. All severe adverse events occurred in patients in the placebo group, including a fall, contusion, and jaw fracture which required hospitalization.
“This analysis suggests that the reduction in drop-seizure frequency achieved with clobazam treatment provides a clinically meaningful benefit by reducing the likelihood of seizure-related injuries,” the authors wrote. “Linking the primary trial end point of seizure reduction with a real-world measure of morbidity offers some validation of that seizure outcome end point, and also suggests that it may be possible to design some trials with more meaningful and clinically relevant end points.”
Isojarvi J, Lee D, Peng G, Sperling MR. Clobazam-treated patients with Lennox-Gastaut syndrome experienced fewer seizure-related injuries than placebo patients during trial OV-1012. Epilepsia. 2016; doi:10.1111/epi.13388.