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

Abstract

Background: The aim of this study was to evaluate the bioequivalence of the test and reference products of ibrutinib capsule (140 mg).

Research design and methods: 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 (C_max, AUC_0-t, and AUC_0-∞) 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 (S_WR) estimated in the study.

Results: RSABE approach was applied to C_max as the corresponding S_WR value exceeded the cutoff value of 0.294, while ABE approach was applied to AUC_0-t and AUC_0-∞ as the corresponding S_WR values were less than 0.294. All three PK parameters (C_max, AUC_0-t, and AUC_0-∞) met the bioequivalence acceptance criteria in both fasting and fed studies.

Conclusions: 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 C_max of ibrutinib.

Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html identifier is CTR20202168.