Results of the 311 study of parampanel showed improvements in response/ seizure frequency regardless of age or concomitant enzyme-inducing anti-seizure drug use.
Robert Flamini, MD
Results from the 311 Core study examining the safety, tolerability, pharmacokinetics, and pharmacodynamics of perampanel demonstrated a generally safe, well-tolerated, and efficacious profile in children with focal seizures (FS) with and without focal to bilateral tonic-clonic seizures (FBTCS), or generalized tonic-clonic seizures (GTCS).
The multi-center, open-label, single-arm study included 180 participants age 4 to less than 12 years with FS (with or without FBTCS) or GTCS. Patients underwent a 4-week pretreatment period, prior to beginning the 23-week treatment period, which included an 11-week titration phase and a 12-week maintenance period, followed by a 4-week follow-up.
Those included in the program had to have a diagnosis of epilepsy with partial-onset seizures (POS), weigh at least 35 pounds, and have had at least 1 brain imaging scan before their first visit to rule out a progressive cause of epilepsy. Those who were breastfeeding or pregnant, had been exposed to perampanel 4 weeks prior to trial, or had participated in another study involving the administration of an investigational drug were excluded from the study.
The investigators assessed patients on multiple endpoints, including safety and tolerability, median percent change in seizure frequency per 28 days from baseline during the treatment period, and 50% responder and seizure-freedom rates during the maintenance period. Additionally, patients were stratified by age (4 to <7 [n= 46] and 7 to <12 [n= 134]), and their concomitant enzyme-inducing anti-seizure drug (EIASD) use.
Of the 180 total participants, 149 had some form of FS, 54 had FBTCS, and 31 had GTCS. Following treatment with adjunctive perampanel, the median percent reduction in FS, FBTCS, and GTCS frequency was 40% (95% CI, 31%-53%; IQR 76), 59% (95% CI, 49%-70%; IQR 49), and 69% (95% CI, 18%-100%; IQR 82), respectively.
Of the patients with FS, 46% reported at least 50% responder rates for total seizures, compared to 55% of patients with FBTCS. The 50% responder rate within the EIASD cohort was 47%, 67%, and 64% in patients with FS, FBTCS, and GTCS, respectively.
There was little variation of seizure frequency from the EIASD cohort. Seizure frequency per 28 days from baseline was 43% in patients with FS age 4 to <7 (95% CI, 26%-56%; IQR 48) and 40% for the 7 to <12 cohort (95% CI, 31%-53%; IQR 81).
“For the EIASD cohort, there was a reduction in seizure frequency and an increase in responder rates (50% and 100%). This suggests no negative impact of concomitant EIASDs on perampanel efficacy in the 311 Core Study,” the study authors concluded.
When the trial concluded, 146 patients (81%) had completed it, with adverse events cited as the most common reason for discontinuation. Treatment-emergent adverse events (TEAEs) occurred in 89% of patients, including 67% of patients who experienced a TEAE related to perampanel. Somnolence was the most observed TEAE, which occurred in 26% of patients. Other common TEAEs included nasopharyngitis in 19% of patients, and dizziness, irritability, and pyrexia, which were all reported in 13% of patients.
In addition to the core study, there will be 2 extension phases as well. Extension A will consist up to a 29-week maintenance period followed by a 4-week follow-up period. Patients who completed extension A will be eligible for Extension B, which will consistent of a treatment phase. The trial is expected to conclude on March 26, 2020.
Fogarasi A, Flamini R, Mathieu Milh, et al. Open-label study to investigate the safety and efficacy of adjunctive perampanel in pediatric patients (4 to <12 years) with inadequately controlled focal seizure or generalized tonic-clonic seizures. Epilepsia. Published online January 7, 2020. doi:10.1111/epi.16413.