Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects

Abstract

Background and objective: VC004 is a novel next-generation tropomyosin receptor kinase (TRK) inhibitor that is approved for the treatment of advanced or metastatic NTRK fusion-positive solid tumors and abrogated the drug resistance of the first-generation TRK inhibitors. The objective of the present study was to evaluate the effect of food on the pharmacokinetics and safety of VC004.

Methods: The study was a randomized, open-label, two-period crossover, single-dose, phase I clinical trial. A total of 16 healthy subjects participated the trial. Subjects fasted for 10 h before drug administration in both fasting and fed states. Subjects received VC004 50 mg orally in the fasting state and after a high caloric food in the fed state. Blood samples at the designated time points were collected to determine the plasma concentration of VC004. Safety evaluation in both the fasted and fed periods were assessed via vital sign monitoring and clinical laboratory tests.

Results: The maximum plasma concentration (C_max) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to C_max (T_max) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of C_max, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC_0-t), and AUC from zero to infinity (AUC_0-∞) for VC004 between the two states were 67.18 (58.16-77.60), 103.59 (95.04-112.92) and 103.55 (95.63-112.11), respectively. No serious adverse events (AEs) occurred; only three grade 1 or grade 2 adverse events occurred in the fasted group, who recovered by the end of the study.

Conclusions: The intake of high calorie food decreased the absorption rate and increased the T_max of VC004, while the AUC values were similar in both groups. No serious adverse event was reported. In conclusion, food does not alter the pharmacokinetics and safety profile of VC004 in a clinically meaningful manner.

Trial registration: ClinicalTrials.gov ID: NCT055528120.

Trial registration: ClinicalTrials.gov NCT0552812.