Higher-dose pregabalin effective for children with focal onset seizures

Treatment with pregabalin at 14 mg/kg/d, but not the lower dose, leads to a lower rate of attacks in children with focal onset seizures (FOS), although both doses are generally safe and well tolerated, a study has shown.

A total of 175 children aged 1 month to <4 years were randomized to receive pregabalin at 14 mg/kg/d (n=34) or 7 mg/kg/d (n=71) or placebo (n=70) for 14 days (5-day dose escalation, 9-day fixed dose including V-EEG monitoring of 48–72 hours over final 3 days) and a 7-day taper phase. The mean age of the cohort was 28.2 months, 59 percent of them were boys, and 30 percent were Asian.

Overall, 33 percent of patients were taking one antiepileptic drug (AED), 50 percent were taking two AEDs, and 17 percent were taking three AEDs. The most common AEDs used were carbamazepine, clonazepam, levetiracetam, oxcarbazepine, phenobarbital, topiramate and valproic acid.

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.

Compared with placebo, the higher pregabalin dose produced a statistically significant 35-percent reduction of log_e (24‐hour seizure rate + 1; p=0.022), the primary study endpoint. This effect was not seen with pregabalin 7 mg/kg/d (p=0.461).

Safety and tolerability of the two pregabalin doses were similar and consistent with the known profile of the drug in older children with epilepsy. The most frequently reported treatment‐emergent adverse events (AEs) across the 7 mg/kg/d, 14 mg/kg/d and placebo treatment arms were somnolence (11.3 percent, 17.6 percent and 5.7 percent) and upper respiratory tract infection (7.0 percent, 11.8 percent and 11.4 percent). All AEs were mild to moderate in severity.