VANCOUVER, BC—An increase in clobazam (Onfi; Lundbeck) dosage of ≥20% during long-term treatment “further improved seizure control in more than 60% of patients with Lennox-Gastaut syndrome who had previously responded to clobazam during lead-in treatment,” results of a post-hoc analysis presented at the 68th Annual AAN Meeting have shown.
In addition, “patients initially treated with lower dosage clobazam and those who had a lower initial response were more likely to experience a positive outcome with clobazam dosage optimization,” reported Robert T. Wechsler, MD, PhD, of the Idaho Comprehensive Epilepsy Center, Boise, ID, and colleagues.
The researchers assessed the rate of successful dosage optimization using data from a Phase 3 multicenter, 36-month open-label extension trial “by examining the effects of clobazam dosage increase on seizure response during the first 12 months of open-label treatment,” he noted.
The extension study comprised patients who had completed 1 of 2 lead-in studies of clobazam for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. In one study, patients received 12 weeks of treatment with placebo or clobazam at doses categorized as low (10mg/day), medium (20mg/day) or high (40mg/day). In the second study, patients received 4 weeks of clobazam at either a low (10mg/day) or high (40mg/day) dose.
“Within 14 days of completing one of the lead-in studies, patients could enroll in the open-label extension and immediately transition to 40mg/day open-label clobazam,” Dr. Wechsler stated. “After 48 hours, dosage changes up to 80mg/day (2.0mg/kg) were permitted.”
Of the 265 patients who entered open-label extension, 78 had received 12 weeks of lead-in clobazam treatment and were ≥25%, ≥50%, and ≥75% responders at the end of lead-in treatment with 12 months of follow-up visits.
The investigators defined a “successful” dosage increase as a ≥20% dosage increase from open-label extension baseline and either improvement in seizure responder status or ≥50% reduction in total seizure frequency.
A total of 59 patients had a ≥20% increase in clobazam dosage; of these, 37 (62.7%) had a successful dosage increase.
“There was a high percentage of successful dosage increase in all baseline responder categories, with the highest rate of successful dosage increase occurring in the patients with the lowest initial seizure response rate,” Dr. Wechsler reported. A total of 11 patients (73.3%) were ≥25% responders; 12 (60.0%) were ≥50% responders, and 14 (58.3%) were ≥75% responders.
In addition, “response to an increase in an open-label clobazam dosage was greatest among patients treated with low or medium double-blind clobazam dosage in the lead-in trial,” he concluded.
Dr. Wechsler has done promotional work and served on an advisory board for Lundbeck LLC.