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Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: A double‐blind, placebo‐controlled, video‐electroencephalographic trial
Author(s) -
Mann Donald,
Antinew Jeremias,
Knapp Lloyd,
Almas Mary,
Liu Jing,
Scavone Joseph,
Yang Ruoyong,
Modequillo Margaret,
Makedonska Iryna,
Ortiz Marilyn,
Kyrychenko Alla,
Nordli Douglas,
Farkas Viktor,
Farkas Mark Kristof
Publication year - 2020
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16466
Subject(s) - pregabalin , placebo , tolerability , medicine , anesthesia , epilepsy , adverse effect , anticonvulsant , randomized controlled trial , electroencephalography , clinical endpoint , adjunctive treatment , psychiatry , alternative medicine , pathology
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 (log e [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 log e (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.