The Bioequivalence of Abexinostat (CRA‐024781) Tosylate Tablets (20 mg) in Chinese Healthy Subjects Under Fasting Conditions

• Published in: Clinical pharmacology in drug development Vol. 13; no. 9; pp. 1061 - 1070
• Main Authors: Li, Xiang, Guo, Wenqiang, Chen, Jian, Tan, Gewen
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.09.2024
• Subjects: abexinostat (CRA‐024781); bioequivalence; healthy subjects; histone deacetylase inhibitor (HDACi); pharmacokinetics
• ISSN: 2160-763X; 2160-7648; 2160-7648
• DOI: 10.1002/cpdd.1448

This study aimed to investigate the pharmacokinetic parameters of single oral administration of postchange and prechange abexinostat (CRA‐024781) tosylate tablets in Chinese healthy subjects under fasting conditions, and assess the bioequivalence (BE) of the 2 formulations (Test [T1] and Reference [T2]). This study was a randomized, open‐label, 2‐formulation, fasting administration, single‐dose, 2‐sequence, 2‐cycle, crossover BE study. Thirty‐six subjects were enrolled in the study and 33 subjects completed 2 cycles. The plasma concentrations were determined by liquid chromatography‐tandem mass spectrometry. The 90% confidence intervals (CIs) for the Cmax, AUC0‐t, and AUC0‐∞ of CRA‐024781 and its 2 major metabolites (PCI‐27789 and PCI‐27887, both metabolites are pharmacologically inactive on HDAC1) fell within the acceptable range of 80%‐125%. The results suggest that the CRA‐024781 test preparation (Test [T1]) is bioequivalent to the reference preparation (Reference [T2]) in healthy Chinese subjects under fasting conditions.