A phase I study of HEC73543, an oral FLT3 inhibitor: the effect of food on pharmacokinetics after oral dosing in healthy Chinese volunteers

ObjectiveThis study evaluated the effect of food on the pharmacokinetics (PK) and safety of HEC73543.MethodsThis randomized, open-label, single-dose, phase I parallel trial included 40 healthy subjects randomized (1:1) to either high-fat or fasted groups. Participants received a single oral dose of 40 mg HEC73543. Blood samples were collected and detected using a validated liquid chromatography tandem mass spectrometry method. PK parameters were calculated using non-compartmental methods. Safety was monitored throughout the study.ResultsFor the HEC73543, the fed-to-fasted ratios were: area under the curve from time 0 to time t (AUC0–t), 219.42% (90% confidence interval [CI]: 173.76, 277.08%); AUC from zero to infinity (AUC0–∞), 255.22% (90% CI: 198.10, 328.80%); and maximum concentration (Cmax), 221.31% (90%CI: 190.57, 257.00%). Similarly, for the metabolite M3, the fed-to-fasted ratios were: AUC0–t, 190.86% (90%CI: 153.26%, 237.68%); AUC0–∞, 190.29% (90% CI: 151.77%, 238.59%); and Cmax, 177.48% (90% CI: 137.80%, 228.58%). Median Tmax of HEC73543 were comparable between the two groups. The most frequently Treatment-Related Adverse Events (TRAEs) were elevated blood triglycerides, oral ulceration, hyperuricemia, diarrhea, thoracalgia. Most TRAEs were Grade 1 or 2.ConclusionHigh-fat food intake enhanced bioavailability and increases the systemic exposure levels of HEC73543 and its metabolite M3.Clinical Trial RegistrationNCT05454098 (http://www.clinicaltrials.gov/).