PMID- 36925997
OWN - NLM
STAT- MEDLINE
DCOM- 20230320
LR  - 20230320
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 17
DP  - 2023
TI  - Effect of Food on the Pharmacokinetics and Safety of a Novel c-Met Inhibitor 
      SCC244: A Randomized Phase I Study in Healthy Subjects.
PG  - 761-769
LID - 10.2147/DDDT.S388846 [doi]
AB  - OBJECTIVE: This study aimed to investigate the effect of food on the 
      pharmacokinetics and safety profiles of SCC244, a novel oral c-Met inhibitor in 
      healthy Chinese male subjects. METHODS: It was a randomized, open-label, and 
      3-period crossover design, single-dose phase I clinical trial. A total of 18 
      healthy male subjects were enrolled. These subjects received a single oral 300 mg 
      dose of SCC244 with a 14-day washout between each period. Blood samples were 
      collected at the designated time points and determined using a validated liquid 
      chromatography tandem mass spectrometry method. Pharmacokinetic parameters were 
      calculated by noncompartmental methods. Tolerability was assessed by physical 
      examination, vital sign measurements, 12-lead ECG, clinical laboratory tests, and 
      adverse events (AEs) monitoring throughout the study. RESULTS: Eighteen eligible 
      subjects were enrolled in the study. The ratios (90% CI) of C(max) values for 
      SCC244 in high-fat and low-fat meal states to that observed in fasted state were 
      194.8% (174.3-217.7%) and 194.6% (174.1-217.5%), respectively. The ratios of 
      AUC(0-t) and AUC(0-inf) in the high-fat meal state versus the fasted state were 
      237.4% (208.7-270.0%) and 235.9% (207.5-268.3%), respectively. The ratios of 
      AUC(0-t) and AUC(0-inf) in the low-fat meal state versus the fasted state were 
      219.2% (192.7-249.3%) and 218.3% (192.0-248.3%), respectively. Median T(max) 
      values and mean t(1/2) were similar in all groups. The most common AEs were 
      headache, blood fibrinogen decreased, head discomfort, dizziness, and protein 
      urine presence. All AEs were Common Terminology Criteria for Adverse Events 
      (CTCAE) grade 1 (except 1 case of grade 2) and have resolved by the end of the 
      study. CONCLUSION: The bioavailability of the tablet formulation of SCC244 was 
      significantly increased when administered with high- and low-fat meals. However, 
      the meals did not affect the median T(max) and t(1/2). Safety under different fed 
      conditions was comparable to fasted conditions in this study.
CI  - (c) 2023 Wu et al.
FAU - Wu, Juan
AU  - Wu J
AUID- ORCID: 0000-0002-0792-5300
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
AD  - Department of Pharmacy, Shanghai Children's Medical Center, School of Medicine, 
      Shanghai JiaoTong University, Shanghai, People's Republic of China.
FAU - Xu, Hongrong
AU  - Xu H
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Ma, Lei
AU  - Ma L
AD  - Haihe Biopharma Co., Ltd, Shanghai, People's Republic of China.
FAU - Chen, Juan
AU  - Chen J
AD  - Haihe Biopharma Co., Ltd, Shanghai, People's Republic of China.
FAU - Yuan, Fei
AU  - Yuan F
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Sheng, Lei
AU  - Sheng L
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Liu, Chao
AU  - Liu C
AUID- ORCID: 0000-0001-5410-5519
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Chen, Weili
AU  - Chen W
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
FAU - Li, Xuening
AU  - Li X
AUID- ORCID: 0000-0003-3899-5245
AD  - Department of Clinical Pharmacology & Cancer Center, ZhongShan Hospital, Fudan 
      University, Shanghai, People's Republic of China.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230310
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Tablets)
SB  - IM
MH  - Humans
MH  - Male
MH  - Healthy Volunteers
MH  - Area Under Curve
MH  - Biological Availability
MH  - Therapeutic Equivalency
MH  - *Fasting
MH  - *Protein Kinase Inhibitors/pharmacokinetics
MH  - Cross-Over Studies
MH  - Food-Drug Interactions
MH  - Administration, Oral
MH  - Tablets
PMC - PMC10013581
OTO - NOTNLM
OT  - SCC244
OT  - c-Met inhibitor
OT  - food effect
OT  - pharmacokinetics
OT  - safety
COIS- Lei Ma and Juan Chen are employees of Haihe Biopharma Co., Ltd. The authors have 
      indicated that they have no other conflicts of interest with regard to the 
      content of this article.
EDAT- 2023/03/18 06:00
MHDA- 2023/03/21 06:00
PMCR- 2023/03/10
CRDT- 2023/03/17 02:40
PHST- 2022/09/05 00:00 [received]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/03/17 02:40 [entrez]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/21 06:00 [medline]
PHST- 2023/03/10 00:00 [pmc-release]
AID - 388846 [pii]
AID - 10.2147/DDDT.S388846 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2023 Mar 10;17:761-769. doi: 10.2147/DDDT.S388846. 
      eCollection 2023.