Bioequivalence evaluation of generic febuxostat versus Feburic® in healthy Chinese subjects: a randomized crossover study.

Abstract

Purpose: Febuxostat, a xanthine oxidase inhibitor, is a first-line treatment for gout with hyperuricemia. This study evaluated the pharmacokinetic (PK) bioequivalence, safety profile, and food effects of a generic febuxostat formulation compared to the reference product (Feburic^®) in healthy Chinese volunteers PATIENTS AND METHODS: In this randomized, open-label, two-sequence, two-period crossover trial, 80 participants (74 males, 6 females) received single 40 mg doses of both test and reference formulations under fasting and fed conditions, separated by a 7-day washout. Plasma concentrations were quantified using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Primary endpoints included peak plasma concentration (C_max), area under the plasma concentration-time curve from time zero to the last time quantifiable time point (AUC_0-t), and area under the plasma concentration-time curve from time zero to infinity (AUC_0-∞), with bioequivalence determined using 90% confidence intervals (CIs) for geometric mean ratios (GMRs).

Results: All 90% CIs for GMRs fell within the 80-125% bioequivalence range (fasting: AUC_0-t 99.08-104.28%, AUC_0-∞ 98.73-103.84%, C_max 92.87-112.14%; fed: AUC_0-t 101.16-106.21%, AUC_0-∞ 101.13-105.94%, C_max 91.72-105.07%). High-fat meals delayed T_max by 0.67 h and Tlag by 0.37 h (p < 0.05) while reducing systemic exposure (C_max by ~ 35%, AUC_0-∞ by ~ 12%; all p < 0.05). Adverse event incidence was 12.8% (fasting) and 25.0% (fed), with no serious adverse events reported.

Conclusion: The generic febuxostat formulation demonstrated PK equivalence to Feburic^® under both fasting and fed conditions, with comparable safety profiles. The observed food effects, while statistically significant, support flexible administration without meal restrictions, meeting pharmacokinetic criteria for consideration as a therapeutic alternative in gout management.

Clinical trial registration: This study was prospectively registered (Registration No. CTR20233483; First Public Release Date: 1 November 2023) in the Chinese Clinical Trial Registration Platform ( http://www.chinadrugtrials.org.cn ), a registry recognized by the Chinese National Medical Products Administration (NMPA). The trial was conducted from 28 November 2023 to 26 December 2023.