The pharmacokinetics of a single intravenous dose of difelikefalin in adolescents aged 12 to 17 years on hemodialysis.
Abstract
Background
The aim of this study was to evaluate the pharmacokinetic profile, safety, and tolerability of a single intravenous bolus injection of difelikefalin in adolescents on maintenance hemodialysis.
Methods
In this multicenter, open-label study, adolescents (12 to 17 years old) received a single difelikefalin dose of 0.5 μg/kg dry body weight at the end of the dialysis. Blood samples were collected over 3 days to assess difelikefalin plasma concentrations, and participants were followed up for adverse events (AEs) for 7-10 days. Key pharmacokinetic parameters were maximum plasma concentration (Cmax), area under the concentration-time curve (AUC) from 0 to 48 h (AUC0-48 h) and AUC extrapolated to infinity (AUCinf). A prespecified numerical comparison of these parameters was conducted against data from a previous study in adults on hemodialysis (NCT02229929).
Results
Eight participants completed the study and seven (3 males and 4 females; aged 12-17 [mean 15.1] years) had evaluable pharmacokinetic data. Mean (standard deviation) Cmax, AUC0-48 h, and AUCinf were 6.03 (1.81) ng/mL, 63.4 (17.4) h ng/mL, and 72.5 (23.7) h ng/mL, respectively. Systemic exposure was comparable between adolescents and adults. One participant developed two mild treatment-related AEs (headache and dizziness), but there were no serious AEs or AEs leading to study withdrawal.
Conclusion
After a single difelikefalin 0.5 μg/kg dose, the overall exposure in adolescents on hemodialysis was comparable to prior adult data, with no new safety signals identified, supporting further evaluation of the 0.5 μg/kg dose in adolescents with moderate-to-severe chronic kidney disease-associated pruritus.