Bioequivalence of generic and branded ibrutinib capsules in healthy Chinese volunteers under fasting and fed conditions: a randomized, four-period, fully replicated, crossover study.

The aim of this study was to evaluate the bioequivalence of the test and reference products of ibrutinib capsule (140 mg). This was a fully replicated crossover study that included 100 healthy Chinese volunteers (50 in the fasting BE study and 50 in the fed BE study). Subjects were assigned to receive a single dose of test or reference product in each treatment period. The bioequivalence of main PK parameters (Cmax, AUC0-t, and AUC0-∞) was evaluated using either the average bioequivalence (ABE) approach or the reference-scaled average bioequivalence (RSABE) approach, depending on the within-subject standard deviation of the reference product (SWR) estimated in the study. RSABE approach was applied to Cmax as the corresponding SWR value exceeded the cutoff value of 0.294, while ABE approach was applied to AUC0-t and AUC0-∞ as the corresponding SWR values were less than 0.294. All three PK parameters (Cmax, AUC0-t, and AUC0-∞) met the bioequivalence acceptance criteria in both fasting and fed studies. The test and reference products of ibrutinib capsule are bioequivalent under both fasting and fed conditions. This study also confirmed high intra-subject variability for the Cmax of ibrutinib. http://www.chinadrugtrials.org.cn/index.html identifier is CTR20202168.