Abstract
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 (AUC(inf)) 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.