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

Ying C. Ou, Richard A. Preston, Thomas C. Marbury, Zhiyu Tang, William Novotny, Manal Tawashi, Ta Kai Li, Srikumar Sahasranaman

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)1355-1363
Number of pages9
JournalLeukemia and Lymphoma
Volume61
Issue number6
DOIs
StatePublished - May 11 2020

Keywords

  • Zanubrutinib
  • hepatic impairment
  • pharmacokinetics
  • safety

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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