Linlin Hu, Qiuyue Sun, Lu Tang, Mingmin Cai, Wei Qian, Ting Dou, Huiping Wang, Yong Wu, Yongqiang Liu
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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.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The maximum plasma concentration (<i>C</i><sub>max</sub>) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to <i>C</i><sub>max</sub> (<i>T</i><sub>max</sub>) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of <i>C</i><sub>max</sub>, the area under the curve of plasma concentration-time from zero to the last measurable concentration (<i>AUC</i><sub>0–<i>t</i></sub>), and <i>AUC</i> from zero to infinity (<i>AUC</i><sub>0–<i>∞</i></sub>) 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.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The intake of high calorie food decreased the absorption rate and increased the<i> T</i><sub>max</sub> 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.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>ClinicalTrials.gov ID: NCT055528120.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":"234 2 1","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects\",\"authors\":\"Linlin Hu, Qiuyue Sun, Lu Tang, Mingmin Cai, Wei Qian, Ting Dou, Huiping Wang, Yong Wu, Yongqiang Liu\",\"doi\":\"10.1007/s40261-023-01334-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background and Objective</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>The maximum plasma concentration (<i>C</i><sub>max</sub>) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to <i>C</i><sub>max</sub> (<i>T</i><sub>max</sub>) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of <i>C</i><sub>max</sub>, the area under the curve of plasma concentration-time from zero to the last measurable concentration (<i>AUC</i><sub>0–<i>t</i></sub>), and <i>AUC</i> from zero to infinity (<i>AUC</i><sub>0–<i>∞</i></sub>) 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. 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Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects
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 (Cmax) of VC004 in fed group decreased by 32.8%, corresponding with the slower absorption rate (time to Cmax (Tmax) delayed by almost 3 h) compared with the fasting group. Ratios of geometric means (GMRs) and 90% confidence intervals (90% CIs) of Cmax, the area under the curve of plasma concentration-time from zero to the last measurable concentration (AUC0–t), and AUC from zero to infinity (AUC0–∞) 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 Tmax 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.
期刊介绍：
Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes:
-Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs.
-Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice.
-Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed.
-Studies focusing on the application of drug delivery technology in healthcare.
-Short communications and case study reports that meet the above criteria will also be considered.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.
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