Pharmacokinetics, Relative Bioavailability, and Safety of the SHR0302 Oral Solution and Tablets: A Single-Center, Randomized, Open-Label, Crossover (Two-Formulation, Two-Period) Phase I Trial in Healthy Chinese Volunteers.

Abstract

Purpose: This study investigates the pharmacokinetic characteristics and relative bioavailability of SHR0302 oral solution and tablets in healthy Chinese male volunteers.

Patients and methods: This single-center, randomized, open-label, crossover (two-formulation, two-period) phase I study enrolled 16 healthy male volunteers. Participants were randomized 1:1 to receive single dose 8mg of either the SHR0302 oral solution or the SHR0302 tablet. Blood samples were collected according to the protocol requirements, and SHR0302 plasma concentrations were analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated using a non-compartmental analysis in Phoenix WinNonlin (version 8.3). Data processing and analysis of pharmacokinetic characteristics and relative bioavailability were conducted using SAS software (version 9.4). Safety was assessed through treatment-emergent adverse events (TEAEs), vital signs, physical examinations, 12-lead electrocardiograms, and laboratory tests.

Results: All 16 enrolled subjects completed the study. The geometric mean ratio (90% confidence interval) for C_max of SHR0302 oral solution versus tablets was 1.04 (0.998, 1.09), and the geometric mean ratios (90% confidence intervals) for AUC₀-_t and AUC₀-_inf were both 1.04 (1.02, 1.06). These results fell entirely within the bioequivalence range of 80% to 125%. Among the 16 subjects, 5 (31.3%) experienced a total of 6 TEAEs, all of which were mild in severity. No serious adverse events were reported.

Conclusion: In healthy Chinese male volunteers, the bioavailability of the SHR0302 oral solution was comparable to that of the SHR0302 tablet. The drug was safe and well tolerated following a single dose.