incb039110 and Liver-Diseases

Itacitinib is a potent, selective JAK-1 inhibitor currently in development for the treatment of chronic graft-vs-host-disease in combination with corticosteroids. Itacitinib is primarily eliminated via cytochrome P450 3A metabolism with minimal renal elimination. The purpose of this open-label study was to investigate the effect of hepatic impairment, as determined by Child-Pugh grade, on itacitinib pharmacokinetics. All participants received a single 300-mg dose of itacitinib orally in the fasted state. Blood samples were collected serially through 96 hours after dosing; 4 hours after dosing, an additional sample was collected for protein binding determination. Participants with moderate hepatic impairment (N = 8) had an approximate 2.5-fold increase in total exposure (area under the plasma concentration-time curve from time 0 to infinity [AUC

Topics: Acetonitriles; Adult; Aged; Area Under Curve; Body Mass Index; Female; Humans; Janus Kinase Inhibitors; Liver Diseases; Liver Function Tests; Male; Metabolic Clearance Rate; Middle Aged; Patient Acuity; Protein Binding; Pyrazoles; Pyrimidines; Pyrroles