809-P: The Effect of Various Degrees of Hepatic Impairment on the Pharmacokinetic Characteristics of Once-Weekly Insulin Icodec

Abstract

Insulin icodec is a novel basal insulin being developed for once-weekly administration. This study investigated if the pharmacokinetic characteristics of icodec are affected by hepatic impairment. In an open-label, parallel-group trial, 25 individuals (13 females/12 males; mean±SD age 54±9 yrs, BMI 28.3±5.2 kg/m2) were allocated to four groups based on hepatic function: normal hepatic function (n=6), mild (Child-Pugh Classification grade A; n=6), moderate (Child-Pugh grade B; n=6), and severe (Child-Pugh grade C; n=7) hepatic impairment. Icodec was administered as a single s.c. dose (1.5 U/kg) followed by blood sampling for pharmacokinetics until 840 h (35 days) post-dose. Total exposure of icodec (AUC0-∞,SD) was greater for mild (by 13%) and moderate (by 15%) hepatic impairment vs normal hepatic function, while no difference was observed for severe hepatic impairment vs normal hepatic function (Figure). Maximum concentration of icodec was not affected by hepatic impairment after a single dose (Cmax,SD) or at simulated steady state (Cmax,SS). In conclusion, the slightly greater total exposure of icodec for mild and moderate hepatic impairment vs normal hepatic function is considered of limited clinical relevance as icodec should be dosed according to individual need. No specific dose adjustment of icodec is required in individuals with hepatic impairment. Disclosure H.Haahr: Employee; Novo Nordisk, Stock/Shareholder; Novo Nordisk. B.Cieslarova: None. A.M.Donatsky: Employee; Novo Nordisk. J.R.Joseph: None. N.R.Kristensen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. V.Kupcová: None. J.R.Hingst: Employee; Novo Nordisk, Research Support; Pfizer Inc. Funding Novo Nordisk