PMID- 38112942
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240108
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 44
IP  - 1
DP  - 2024 Jan
TI  - Food Effect on the Pharmacokinetics of VC004, a Tropomyosin Receptor Kinase 
      Inhibitor: A Randomized Crossover Trial in Healthy Chinese Subjects.
PG  - 79-85
LID - 10.1007/s40261-023-01334-y [doi]
AB  - 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-infinity)) 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.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Hu, Linlin
AU  - Hu L
AUID- ORCID: 0000-0002-7545-5195
AD  - Department of Pharmacy, Nanjing Zhongda Hospital, School of Medicine, Southeast 
      University, Nanjing, 210009, China. eliza50@sina.com.
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China. eliza50@sina.com.
FAU - Sun, Qiuyue
AU  - Sun Q
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Tang, Lu
AU  - Tang L
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Cai, Mingmin
AU  - Cai M
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Qian, Wei
AU  - Qian W
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Dou, Ting
AU  - Dou T
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Wang, Huiping
AU  - Wang H
AD  - Department of Phase I Clinical Trial Unit, Nanjing Zhongda Hospital, School of 
      Medicine, Southeast University, Nanjing, 210009, China.
FAU - Wu, Yong
AU  - Wu Y
AD  - Jiangsu Vcare PharmaTech Co., Ltd., Nanjing, China.
FAU - Liu, Yongqiang
AU  - Liu Y
AD  - Jiangsu Vcare PharmaTech Co., Ltd., Nanjing, China.
LA  - eng
SI  - ClinicalTrials.gov/NCT0552812
GR  - No. 81503340/the National Natural Science Foundation of China/
GR  - No. SY202306-4/Shijiazhuang Pharmaceutical Foundation of Jiangsu Pharmaceutical 
      Association/
GR  - No. Q202203/the CHIA TAI TIAQING Pharmaceutical Foundation of Jiangsu 
      Pharmaceutical Association/
GR  - BK20150645/Basic Research Program of Jiangsu Province/
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231219
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Tropomyosin)
RN  - 0 (Tablets)
SB  - IM
MH  - Humans
MH  - *Tropomyosin
MH  - Cross-Over Studies
MH  - Healthy Volunteers
MH  - *Fasting
MH  - Therapeutic Equivalency
MH  - Area Under Curve
MH  - China
MH  - Food-Drug Interactions
MH  - Administration, Oral
MH  - Tablets
EDAT- 2023/12/19 19:55
MHDA- 2024/01/08 06:42
CRDT- 2023/12/19 11:23
PHST- 2023/11/30 00:00 [accepted]
PHST- 2024/01/08 06:42 [medline]
PHST- 2023/12/19 19:55 [pubmed]
PHST- 2023/12/19 11:23 [entrez]
AID - 10.1007/s40261-023-01334-y [pii]
AID - 10.1007/s40261-023-01334-y [doi]
PST - ppublish
SO  - Clin Drug Investig. 2024 Jan;44(1):79-85. doi: 10.1007/s40261-023-01334-y. Epub 
      2023 Dec 19.