The pharmacokinetics and safety of single-dose zanubrutinib (80 mg) were assessed in subjects with mild, moderate, and severe hepatic impairment (n = 6 each, Child-Pugh class A, B, and C) relative to healthy controls (n = 11). Zanubrutinib median Tmax was 1.25-2.25 h in all groups. Compared to control group, mean zanubrutinib exposure (AUC0-inf) in the mild and moderate hepatic impairment groups was increased by 1.1- and 1.2-fold, which is within the range of PK variability for zanubrutinib. The total and unbound AUC of zanubrutinib were 1.60- and 2.9-fold higher in subjects with severe hepatic impairment compared to healthy controls. Terminal half-life was comparable between subjects with hepatic impairment and matched healthy controls. Zanubrutinib was generally well-tolerated when administered as a single, 80-mg dose to subjects in this study. Results of this study will be used, in conjunction with clinical safety and efficacy data, to develop dose recommendations for patients with hepatic impairment.
Keywords: Zanubrutinib; hepatic impairment; pharmacokinetics; safety.