Volume 7, Issue 4 p. 435-440
Original Manuscript

Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects

Tommy T. Cheung

Tommy T. Cheung

Phase 1 Clinical Trials Centre, The University of Hong Kong, Hong Kong SAR

Search for more papers by this author
Ahmed Hamed Salem

Corresponding Author

Ahmed Hamed Salem

AbbVie Inc., North Chicago, IL, USA

Corresponding Author:

Ahmed Hamed Salem, PhD, Clinical Pharmacology and Pharmacometrics, AbbVie Inc., Dept. R4PK, Bldg. AP31-3, 1 North Waukegan Road, North Chicago, IL 60064

(e-mail: [email protected])

Search for more papers by this author
Rajeev M. Menon

Rajeev M. Menon

AbbVie Inc., North Chicago, IL, USA

Search for more papers by this author
Wijith P. Munasinghe

Wijith P. Munasinghe

AbbVie Inc., North Chicago, IL, USA

Search for more papers by this author
Orlando F. Bueno

Orlando F. Bueno

AbbVie Inc., North Chicago, IL, USA

Search for more papers by this author
Suresh K. Agarwal

Suresh K. Agarwal

AbbVie Inc., North Chicago, IL, USA

Search for more papers by this author
First published: 23 October 2017
Citations: 14

Abstract

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 Cmax, AUCinf, 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 Cmax and AUCinf 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.