Efficacy and safety of pregabalin as adjunctive treatment for children (aged 4-16 years) with partial-onset seizures, hereafter termed focal onset seizures for this study, was evaluated. This double-blind, randomized, placebo-controlled, international study had 3 phases: 8-week baseline, 12-week double-blind treatment (2-week dose escalation; 10-week fixed dose), and 1-week taper. Selection criteria included experiencing focal onset seizures and receiving a stable regimen of 1 to 3 antiepileptic drugs. Study treatments were pregabalin 2.5 mg/kg/d, 10 mg/kg/d, or placebo; doses were increased to 3.5 or 14 mg/kg/d for subjects weighing <30 kg. The key endpoints were change in loge(28-day seizure rate), achieving a ≥50% seizure responder rate, safety, and tolerability during double-blind treatment. Subjects (n = 295; mean age 10.2 years, 55% male, 69% white) were randomized to pregabalin 2.5 mg/kg/d (n = 104), 10 mg/kg/d (n = 97), or placebo (n = 94). A statistically significant reduction in loge(28-day seizure rate) was demonstrated with pregabalin 10 mg/kg/d (a 19.9% improvement over placebo; P = .0185). Seizure frequency was numerically improved (statistically nonsignificant) with pregabalin 2.5 mg/kg/d ( P = .2577). Responder rate significantly favored pregabalin 10 mg/kg/d (40.6%, P = .0068) compared with placebo (22.6%) and was numerically improved with pregabalin 2.5 mg/kg/d (29.1%, P = .2600). Common adverse events (≥10% of any group) in 10 mg/kg/d, 2.5 mg/kg/d, and placebo groups, respectively, included somnolence (25.8%, 17.3%, 13.8%), increased weight (13.4%, 3.8%, 4.3%), and increased appetite (10.3%, 6.7%, 4.3%). Pregabalin 10 mg/kg/d demonstrated efficacy in seizure frequency reduction in children with focal onset seizures compared with placebo, and both pregabalin doses were generally safe and well tolerated. www.clinicialtrials.gov identifier NCT01389596; EudraCT #2010-020852-79.
Keywords: children; focal onset seizures; pediatric; pregabalin.