Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the 
treatment of several inflammatory autoimmune diseases, including rheumatoid 
arthritis. Upadacitinib is a nonsensitive substrate for metabolism by cytochrome 
P450 3A enzymes. This open-label, single-dose, multicenter study assessed the 
pharmacokinetics of upadacitinib following oral administration of a single 15-mg 
dose of the upadacitinib extended-release formulation in subjects with mild (n = 
6) and moderate (n = 6) hepatic impairment relative to demographically matched 
healthy subjects (n = 6). Subjects were assigned to 1 of the 3 groups according 
to the Child-Pugh classification. Relative to subjects with normal hepatic 
function, the ratios (90% confidence intervals) of upadacitinib area under the 
plasma concentration-versus-time profile from time 0 to infinity (AUCinf ) for 
subjects with mild and moderate hepatic impairment were 1.28 (0.91-1.79) and 
1.24 (0.87-1.76), respectively. The central ratios of upadacitinib maximum 
observed concentration (Cmax ) were 1.04 (0.77-1.39) and 1.43 (1.05-1.95) in 
subjects with mild and moderate hepatic impairment, respectively, compared with 
subjects with normal hepatic function. No clinically significant changes in 
vital signs or hematology measurements were observed, and no new safety events 
were identified in this study. These results indicate that mild and moderate 
hepatic impairment has no clinically relevant effect on upadacitinib 
pharmacokinetics.