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

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, AUC, and AUC) 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) estimated in the study.

RESULTS

RSABE approach was applied to C as the corresponding S value exceeded the cutoff value of 0.294, while ABE approach was applied to AUC and AUC as the corresponding S values were less than 0.294. All three PK parameters (C, AUC, and AUC) 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 of ibrutinib.

CLINICAL TRIAL REGISTRATION

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