A phase 1, open-label, single-dose study of the pharmacokinetics of zanubrutinib in subjects with varying degrees of hepatic impairment

Abstract

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 T_max was 1.25–2.25 h in all groups. Compared to control group, mean zanubrutinib exposure (AUC_0–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

Acknowledgements

The authors wish to thank all the subjects, study coordinators, and support staff who contributed to this study.

Disclosure statement

YO, ZT, WN, MT, TKL, SS hold stock in BeiGene. Thomas Marbury is an employee and equity owner of Orlando Clinical Research Center.

Additional information

Funding

Editorial assistance was provided by Erin Spohr of Ashfield Healthcare Communications, and funded by BeiGene, Inc.