The pharmacokinetics of a single intravenous dose of difelikefalin in adolescents aged 12 to 17 years on hemodialysis.

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.