Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: A double‐blind, placebo‐controlled, video‐electroencephalographic trial

Objective To evaluate the efficacy and safety of pregabalin as adjunctive treatment for children (aged 1 month‐<4 years) with focal onset seizures (FOS) using video‐electroencephalography (V‐EEG). Methods This randomized, placebo‐controlled, international study included V‐EEG seizure monitoring (48‐72 hours) at baseline and over the last 3 days of 14‐day (5‐day dose escalation; 9‐day fixed dose) double‐blind pregabalin treatment (7 or 14 mg/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. Results Overall, 175 patients were randomized (mean age = 28.2 months; 59% male, 69% white, 30% Asian) in a 2:1:2 ratio to pregabalin 7 or 14 mg/kg/d (n = 71 or n = 34, respectively), or placebo (n = 70). Pregabalin 14 mg/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 7 mg/kg/d (n = 59; P = .461). The most frequently reported treatment‐emergent AEs for pregabalin 7 mg/kg/d, 14 mg/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. Significance Pregabalin 14 mg/kg/d (but not 7 mg/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 1 month to <4 years of age with FOS. Safety and tolerability were consistent with the known profile of pregabalin in older children with epilepsy.