Abstracts

Rationale: Pregabalin is approved as adjunctive therapy for partial onset seizures (POS) in patients 4 years of age and older in the United States, and in adults in the European Union and multiple other countries. This randomized, placebo-controlled study evaluated the efficacy and safety of 2 dose levels of pregabalin as adjunctive therapy for POS in children (1 month to <4 years of age).  Methods: This double-blind (DB), multinational (52 centers in 22 countries) study had 3 phases: 1) Baseline video-electroencephalogram (V-EEG) recording of 48-72 hours, 2) 14 day DB treatment (5-day dose escalation; 9-day fixed-dose) including V-EEG recording of 48–72 hours over the final 3 days, and 3) 7-day taper. Subjects were experiencing POS and were treated with a stable regimen of 1–3 antiepileptic drugs. Subjects were randomized in a 2:1:2 ratio to receive pregabalin 7 mg/kg/day or 14 mg/kg/day, or placebo, respectively. Baseline and DB V-EEG recordings were read by a central reader for partial seizure counting and duration of V-EEG recording, from which the seizure rates were calculated. The primary efficacy endpoint was the log-transformed 24-hour seizure rate (log_e[24-hour seizure rate]) of all POS. The 50% responder rate, safety, and tolerability were evaluated. Results: Overall, 175 subjects were randomized (pregabalin 7 mg/kg/day n=71, 14 mg/kg/day n=34, placebo n=70). The mean age of enrolled subjects was 28.2 months, with the youngest subject being 3 months old. Of these subjects, 59% were male, 68.6% were white, and 29.7% were Asian. The primary efficacy analysis showed a statistically significant reduction in seizure frequency with pregabalin 14 mg/kg/day (log_e[24-hour seizure rate]) compared with placebo, corresponding to 35% improvement relative to placebo (P=0.0223). The reduction in seizure frequency was not statistically significant with pregabalin 7 mg/kg/day (P=0.4606). No significant differences were noted in responder rate with either pregabalin treatment group (14 mg/kg/day, 53.6%; 7 mg/kg/day, 30.5%) versus placebo (41.5%). Adverse events (AEs) were all mild or moderate in intensity. No new or unexpected AEs were reported relative to the AE profile in patients with POS 4 years of age and older. Treatment-emergent serious AEs (SAEs) were reported for 5 subjects, including 1 treated with pregabalin 14 mg/kg/day (pneumonia, requiring hospitalization) and 4 treated with placebo (acute rhinitis, increasing frequency of seizures, dehydration, choking). None of these were considered treatment-related and all resolved without sequelae. Six of the 175 randomized subjects discontinued the study and 3 of those were from the placebo group. No discontinuations due to AEs were reported for pregabalin-treated subjects. Conclusions: Pregabalin 14 mg/kg/day demonstrated efficacy in significantly reducing POS frequency compared with placebo in pediatric subjects (1 month to <4 years of age), and both pregabalin 7 and 14 mg/kg/day were generally safe and well tolerated.www.clinicaltrials.gov identifier NCT02072824 Funding: This study was funded by Pfizer.