Pregabalin adjunctive therapy for focal onset seizures in children 1 month to

Abstract

To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1month-<4years) with focal onset seizures (FOS) using video-electroencephalography (V-EEG). This randomized, placebo-controlled, international study included V-EEG seizure monitoring (48-72hours) at baseline and over the last 3days of 14-day (5-day dose escalation; 9-day fixed dose) double-blind pregabalin treatment (7 or 14mg/kg/d in three divided doses). This was followed by a double-blind 1-week taper. The primary efficacy endpoint was log-transformed seizure rate (loge [24-hour seizure rate+1]) for all FOS recorded during the double-blind V-EEG monitoring, evaluated in subjects who took ≥1 dose of study medication, experienced ≥1 baseline seizure(s), and had a treatment phase V-EEG. Safety and tolerability were assessed by adverse events (AEs), clinical laboratory data, physical/neurological examinations, vital signs, and electrocardiograms. Overall, 175 patients were randomized (mean age = 28.2months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7or 14mg/kg/d (n=71 or n=34, respectively), or placebo (n=70). Pregabalin 14mg/kg/d (n=28) resulted in a statistically significant 35% reduction of loge (24-hour seizure rate+1) versus placebo (n=53; P=.022), an effect that was not observed with pregabalin 7mg/kg/d (n=59; P=.461). The most frequently reported treatment-emergent AEs for pregabalin 7 mg/kg/d, 14mg/kg/d, and placebo, respectively, were somnolence (11.3%, 17.6%, and 5.7%) and upper respiratory tract infection (7.0%, 11.8%, and 11.4%). All AEs were mild to moderate in severity. Pregabalin 14mg/kg/d (but not 7mg/kg/d) significantly reduced seizure rate in children with FOS, when assessed using V-EEG, compared with placebo. Both pregabalin dosages were generally safe and well tolerated in children 1month to <4years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.