PMID- 36408263
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221122
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Safety, tolerability and pharmacokinetics of WXFL10203614 in healthy Chinese 
      subjects: A randomized, double-blind, placebo-controlled phase Ⅰ study.
PG  - 1057949
LID - 10.3389/fphar.2022.1057949 [doi]
LID - 1057949
AB  - Objective: This study was conducted to investigate the safety, tolerability and 
      pharmacokinetics (PK) of WXFL10203614 after single and multiple oral doses in 
      healthy Chinese subjects. Methods: A single-center, randomized, double-blind, 
      placebo-controlled phase Ⅰ study was performed on healthy Chinese subjects. In 
      the single-dose study, Subjects were randomized into 7 dose levels of 
      WXFL10203614 (1 mg group, n = 2; 2, 5, 10, 17, 25 and 33 mg groups with placebo, 
      8 subjects per group, 2 of them given placebo). In the multiple-dose study, 
      subjects received 5 or 10 mg WXFL10203614 once daily (QD), 5 mg twice daily (BID) 
      or placebo for 7 consecutive days. Safety, tolerability and PK of WXFL10203614 
      were all assessed. Results: A total of 592 subjects were screened, 50 subjects 
      were enrolled in the single-dose study and 30 in the multiple-dose study. All 
      adverse events (AEs) were mild or moderate and resolved spontaneously. No Serious 
      Adverse Events (SAEs) or deaths were reported during the study. WXFL10203614 was 
      absorbed rapidly after dosing with T(max) of 0.48-0.98 h, C(max), AUC(0-t) and 
      AUC(0-infinity) were all increased in a dose-related manner over the range of 1-33 mg. 
      Renal excretion was the major route of elimination of WXFL10203614. Steady-state 
      PK parameters (C(max,ss), AUC(0-t,ss) and AUC(0-infinity,ss)) were elevated after 
      once-daily administration of 5-10 mg WXFL10203614 and non- and weak drug 
      accumulations were observed, whereas moderate drug accumulation occurred in the 
      5 mg BID group. Conclusion: WXFL10203614 exhibited good safety, tolerability and 
      favorable PK profiles in healthy Chinese subjects, supporting further clinical 
      development in patients with rheumatoid arthritis. Clinical Trials Registration 
      Number: http://www.chinadrugtrials.org.cn/index.html, #CTR20190069 and 
      CTR20200143.
CI  - Copyright (c) 2022 Huang, Ding, Que, Chu, Shi, Qian, Qin, Chen, Gu, Wang, Zhang, Xu 
      and He.
FAU - Huang, Kai
AU  - Huang K
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Ding, Ying
AU  - Ding Y
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Que, Linling
AU  - Que L
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Chu, Nannan
AU  - Chu N
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Shi, Yunfei
AU  - Shi Y
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Qian, Zhenzhong
AU  - Qian Z
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Qin, Wei
AU  - Qin W
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Chen, Yuanxin
AU  - Chen Y
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Gu, Xianghong
AU  - Gu X
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Wang, Jiakun
AU  - Wang J
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
FAU - Zhang, Zhiwei
AU  - Zhang Z
AD  - Wuxi Fuxin Pharmaceutical Research and Development Co, Ltd, Wuxi, China.
FAU - Xu, Jianguo
AU  - Xu J
AD  - Wuxi Fuxin Pharmaceutical Research and Development Co, Ltd, Wuxi, China.
FAU - He, Qing
AU  - He Q
AD  - Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing 
      Medical University, Wuxi, China.
LA  - eng
PT  - Journal Article
DEP - 20221104
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9671933
OTO - NOTNLM
OT  - JAK1 inhibitor
OT  - WXFL10203614
OT  - first-in-human
OT  - pharmacokinetics
OT  - rheumatoid arthritis
COIS- Authors ZZ and JX were employed by Wuxi Fuxin Pharmaceutical Research and 
      Development Co, Ltd. The remaining authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2022/11/22 06:00
MHDA- 2022/11/22 06:01
PMCR- 2022/11/04
CRDT- 2022/11/21 04:50
PHST- 2022/09/30 00:00 [received]
PHST- 2022/10/18 00:00 [accepted]
PHST- 2022/11/21 04:50 [entrez]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2022/11/22 06:01 [medline]
PHST- 2022/11/04 00:00 [pmc-release]
AID - 1057949 [pii]
AID - 10.3389/fphar.2022.1057949 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Nov 4;13:1057949. doi: 10.3389/fphar.2022.1057949. 
      eCollection 2022.