Perampanel safe for kids with epilepsy
Administering daily oral doses of adjunctive perampanel is safe and well tolerated in the treatment of young and older children with focal seizures (FS) or generalized tonic‐clonic seizures (GTCS), in addition to yielding about 40–70 percent reduction in seizure frequency, according to data from the open-label 311 Core Study.
“As safety data cannot be extrapolated from adults to children, separate open‐label clinical studies involving ≥100 patients are required to adequately assess drug safety in patients ≥4 years of age,” researchers said.
“The safety and efficacy outcomes from 311 Core Study are consistent with previous analyses of perampanel in adolescent and adult populations,” they added. [Neurology 2012;79:589-596; Epilepsia 2013;54:117-125; Neurology 2015;85:950-957]
The single-arm, open-label study included 180 children aged 4 to <12 years with inadequately controlled FS (n=149), FS with focal to bilateral tonic‐clonic seizures (FBTCS; n=54) or GTCS (n=31). The study comprised a core treatment phase (titration, maintenance) plus extensions phases.
During the treatment phase, perampanel oral suspension was administered once daily at bedtime. Over 11 weeks, dose was titrated in increments of 2 mg/day weekly from a starting dose of 2 or 4 mg/day up to 8 mg/day for patients not receiving concomitant enzyme‐inducing antiseizure drug (EIASD) and up to 12 mg/day for those taking concomitant EIASDs. Patients continued treatment at the dose level achieved for 12 weeks and were followed-up for 4 weeks post-treatment.
Patients who completed the treatment phase were eligible to participate in extension A (29-week maintenance and 4-week follow‐up). After completion of extension A, patients enrolled in Japan and countries where an Extended Access Program cannot be implemented could enter extension B.
A total of 146 patients (81 percent) completed the treatment phase. Mean daily perampanel dose was 7.0 mg/day, with the median duration of exposure being 22.9 weeks. The most common reason for discontinuation was adverse event (AE; n=14; 8 percent). [Epilepsia 2020;doi:10.1111/epi.16413]
The incidence of treatment‐emergent AEs (TEAEs; 89 percent overall) was similar in patients with FS (with/without FBTCS) and those with GTCS. Somnolence (26 percent) and nasopharyngitis (19 percent) were the most frequently reported TEAEs.
“Antiseizure drugs have the potential to exert detrimental effects on cogniti[on] and compromise patient well‐being. Perampanel did not produce any clinically significant changes in cognitive function at week 23 compared with baseline,” the researchers noted.
Median percent reductions in seizure frequency per 28 days from baseline were 40 percent in the FS group, 59 percent in the FBTCS group and 69 percent in the GTCS group. The corresponding rates for 50-percent response and seizure‐freedom were as follows: 47 percent and 12 percent in FS; 65 percent and 19 percent in FBTCS; and 64 percent and 55 percent in GTCS. These improvements were observed regardless of age or concomitant EIASD use.
“Perampanel is a noncompetitive, selective α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist indicated in patients with FS or GTCS,” the researchers said.
The drug is approved in more than 50 countries, including the US and Japan and others in Europe and in Asia, as adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in epileptic patients aged ≥12 years.