Relative Bioavailability, Food Effect, and Bioequivalence Studies to Assess a New Zanubrutinib 160-mg Tablet: Results From 2 Phase 1 Studies in Healthy Volunteers.

Abstract

Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor approved for treating B-cell malignancies. Two phase 1 studies evaluated a new 160-mg zanubrutinib tablet versus 80-mg capsules. In study BGB-3111-115 (n = 43), a randomized 3-period crossover trial, relative bioavailability and food effects were assessed. Under fasted conditions, systemic exposure (area under the concentration-time curve [AUC]) was comparable between tablets and capsules at both 160- and 320-mg doses. A high-fat meal increased tablet maximum plasma concentration (C_max) by 47%-79% but had minimal effect on AUC (<18%), supporting administration with or without food. Study BGB-3111-114 (n = 58) was a randomized, replicate crossover study that evaluated bioequivalence (BE) under fasted conditions. Geometric mean ratios of AUC_0-t and AUC_0-∞ (tablets vs capsules) were 1.00 (90% confidence interval [CI] 0.95-1.05) and 0.99 (90% CI 0.94-1.04), meeting BE criteria. Tablet C_max was modestly higher (geometric mean ratio 1.22, 90% CI 1.14-1.30), with no expected clinical impact based on established zanubrutinib exposure-response relationships. Both formulations were well tolerated, with no serious adverse events. In vitro testing showed tablets readily dispersed into a stable suspension suitable for nasogastric tube administration. Together, these results supported zanubrutinib tablets as a flexible alternative to capsules, with the potential to reduce pill burden (4 capsules vs 2 tablets) and improve long-term adherence.