Effects of Food on the Pharmacokinetics and Safety of HA121-28 Tablet, a Novel Multi-Targeting Tyrosine Kinase Inhibitor, in Healthy Chinese Subjects: A Phase I Clinical Trial

Purpose: HA121-28, a novel multi-targeting tyrosine kinase inhibitor, has dual efficacy against tumor growth and neovascularization. The objectives of this study were to assess the effect of high-fat and high-calorie food on the pharmacokinetic (PK) profile and safety of HA121-28 tablet in healthy subjects. Patients and Methods: A single-dose, randomized, open-label, two-period, crossover-designed phase I clinical trial was conducted. Subjects received 200 mg HA121-28 in the fasted state or with high-fat and high-calorie breakfast. The effects of high-fat and high- calorie food on the PK profile and safety of HA121-28 were evaluated by using noncompartmental analysis and whole-process safety assessment. Results: Twenty subjects were successfully completed the trial. The geometric mean ratios (GMRs) for the peak concentration in plasma (C-max), area under the curve from zero to the time point (AUC(last) ), and area under the curve from zero to infinite (AUCinf) postprandially versus fasted were 108.45% (98.51% - 119.40%), 105.23% (100.25% - 110.47%), and 104.14% (97.41% - 111.34%), respectively. The majority of reported adverse events were graded as either level 1 or 2 in severity and recovered spontaneously without any interventions. Conclusion: The exposure of HA121-28 was not significantly affected by the high-fat and high-calorie food. The clinical application of HA121-28 tablet can be recommended for use in both fasted and postprandial states.