Pharmacokinetics and safety of dasatinib and its generic: a phase I bioequivalence study in healthy Chinese subjects.

BACKGROUND: Dasatinib (Sprycel®) is a tyrosine kinase inhibitor for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia.

RESEARCH DESIGN & METHODS: We designed a phase I clinical study to demonstrate that the dasatinib tablet (YiNiShu®) (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and Dasatinib (Bristol Myers Squibb) were bioequivalent under fasting and fed conditions. The whole study was structured into the fasting trial and the postprandial trial. Each period, subjects were given 50 mg dasatinib or its generic. Plasma concentration was analyzed by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. The RSABE (reference scale average bioequivalence) and ABE (average bioequivalence) methods were employed to assess bioequivalence by pharmacokinetics (PK) parameters for a highly variable drug.

RESULTS: 32 and 24 eligible volunteers were enrolled in the fasting and postprandial trials, respectively. In the fasting trial, the RSABE method was performed, and point estimates of Cmax , AUC0-t , and AUC0-∞ met the bioequivalence criteria. In the postprandial trial, the ABE method was performed, and the 90% CI of the geometric mean ratio (GMR) for PK parameters met the requirements of bioequivalence standards.

CONCLUSION: The results proved that the PK parameters of the two drugs were similar and bioequivalent, indicating that both drugs had a good safety profile.

CLINICAL TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (Number: NCT05640804) and Drug Clinical Trial Registration and Information Disclosure Platform (Number: CTR20181708).