Premium
Pharmacokinetics of the BCL‐2 Inhibitor Venetoclax in Healthy Chinese Subjects
Author(s) -
Cheung Tommy T.,
Salem Ahmed Hamed,
Me Rajeev M.,
Munasinghe Wijith P.,
Bueno Orlando F.,
Agarwal Suresh K.
Publication year - 2018
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.395
Subject(s) - venetoclax , pharmacokinetics , medicine , regimen , pharmacology , oncology , gastroenterology , chronic lymphocytic leukemia , leukemia
Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult‐to‐treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first‐generation Han Chinese subjects received a single 100‐mg dose of venetoclax following a low‐fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD C max , AUC inf , and terminal half‐life were 1.0 ± 0.32 μg/mL, 12.6 ± 5.4 μg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax C max and AUC inf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non‐Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure–response relationship of venetoclax in non‐Asian CLL subjects, a 400‐mg once‐daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open‐label study in Chinese subjects with R/R CLL.