Pharmacokinetics of Nintedanib in Subjects With Hepatic Impairment

Nintedanib is an intracellular inhibitor of tyrosine kinases used in the treatment of non–small cell lung cancer and idiopathic pulmonary fibrosis (IPF). This phase 1 open‐label study investigated the influence of mild and moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of nintedanib following oral administration of a single 100‐mg dose. Subjects with hepatic impairment classified as Child‐Pugh A (mild hepatic impairment) or Child‐Pugh B (moderate hepatic impairment) were eligible. The control group comprised healthy matched subjects. Primary end points were C(max) and AUC(0–∞) of nintedanib. Thirty‐three subjects received nintedanib (8 in each of the Child‐Pugh A and Child‐Pugh B groups and 17 controls). The shape of the plasma concentration–time curve for nintedanib was similar between Child‐Pugh A or B and healthy subjects. Nintedanib exposure was ∼2‐fold higher in Child‐Pugh A subjects and ∼8‐fold higher in Child‐Pugh B subjects than in healthy subjects. Adverse events were reported in 3 Child‐Pugh B subjects (37.5%), no Child‐Pugh A subjects, and 3 healthy subjects (17.6%). In conclusion, exposure to nintedanib was higher in Child‐Pugh A and B subjects than in matched healthy subjects. A single dose of nintedanib 100 mg had an acceptable safety and tolerability profile in subjects with hepatic impairment. Results of this dedicated phase 1 study are in line with exploratory investigations into the PK of nintedanib in patients with advanced solid tumors or IPF and hepatic impairment.