PMID- 37551782
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 16
IP  - 10
DP  - 2023 Oct
TI  - A randomized, controlled single, and multiple ascending dose trial of the safety, 
      pharmacokinetics and pharmacodynamics of SN1011 in healthy subjects.
PG  - 1982-1996
LID - 10.1111/cts.13606 [doi]
AB  - The purpose of this study was to investigate the safety, tolerability, 
      pharmacokinetics, and pharmacodynamics of SN1011, a novel Bruton tyrosine kinase 
      (BTK) inhibitor, and food effects in healthy subjects. In this phase I trial, 
      subjects received single ascending doses (SADs) of SN1011 (100 to 800 mg), 
      multiple ascending doses (MADs) of SN1011 (200 to 600 mg), or placebo q.d. 
      Additionally, 12 subjects randomly received a single dose of SN1011 600 mg under 
      fasting states and then fed states, vice versa. Safety was assessed per Common 
      Terminology Criteria for Adverse Events version 5.0. Pharmacokinetic parameters 
      were calculated by noncompartmental analysis and BTK receptor occupancy in 
      peripheral blood monocytes was determined. Seventy-one healthy subjects were 
      dosed in five SAD cohorts, three MAD cohorts, and one food effect cohort, with 57 
      receiving SN1011 and 14 receiving placebo. No serious adverse events (AEs) were 
      reported. There was no correlation between AE occurrences and SN1011 exposure. 
      The three most frequent AEs with SN1011 were increased blood triglycerides, 
      decreased neutrophil count, and decreased leucocyte count. SN1011 exhibited a 
      dose-proportional increase in maximum plasma concentration and area under the 
      time concentration curve following single and multiple dose administrations, with 
      an accumulation ratio of 1.5 to 2.2 after multiple dose administrations. No 
      difference in SN1011 exposure was observed between fed states. BTK receptor 
      occupancy remained above 83% over 24 h after single administration and remained 
      above 80% for the MAD groups for 10 days of continuous q.d. administration. 
      SN1011 was well-tolerated and safe after single or multiple exposures to healthy 
      subjects, supporting further clinical development of SN1011 for treatment of 
      autoimmune diseases.
CI  - (c) 2023 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Zhu, Leilei
AU  - Zhu L
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Shi, Rong
AU  - Shi R
AD  - Surgery Intensive Care Unit, Shuguang Hospital affiliated to Shanghai University 
      of Traditional Chinese Medicine, Shanghai, China.
FAU - Zhao, Tongfang
AU  - Zhao T
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Ye, Yujie
AU  - Ye Y
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Tang, Jie
AU  - Tang J
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Hu, Yihui
AU  - Hu Y
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Peng, Peng
AU  - Peng P
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Wang, Dong
AU  - Wang D
AD  - SinoMab Bioscience Limited, Hong Kong, China.
AD  - MediNexus Pharma (Suzhou) Limited, Suzhou, China.
FAU - Chong, Clement
AU  - Chong C
AD  - SinoMab Bioscience Limited, Hong Kong, China.
AD  - MediNexus Pharma (Suzhou) Limited, Suzhou, China.
FAU - Xu, Guolin
AU  - Xu G
AD  - SinoMab Bioscience Limited, Hong Kong, China.
AD  - MediNexus Pharma (Suzhou) Limited, Suzhou, China.
FAU - Leung, Shui-On
AU  - Leung SO
AD  - SinoMab Bioscience Limited, Hong Kong, China.
AD  - MediNexus Pharma (Suzhou) Limited, Suzhou, China.
FAU - Yuan, Wei'an
AU  - Yuan W
AUID- ORCID: 0000-0002-6072-118X
AD  - Clinical Research Center, Shuguang Hospital affiliated to Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230816
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
SB  - IM
MH  - Humans
MH  - Healthy Volunteers
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Area Under Curve
MH  - *Fasting
PMC - PMC10582678
COIS- This trial was sponsored by SinoMab BioScience Limited. SinoMab was involved in 
      the study design, collection, analysis, and interpretation of data. Dong Wang, 
      Clement Chong, Guolin Xu, and Shui-on Leung were full-time employees of SinoMab 
      BioScience Limited. All other authors declared no competing interests for this 
      work.
EDAT- 2023/08/08 12:42
MHDA- 2023/10/23 12:43
PMCR- 2023/08/16
CRDT- 2023/08/08 06:53
PHST- 2023/06/27 00:00 [revised]
PHST- 2023/03/15 00:00 [received]
PHST- 2023/07/18 00:00 [accepted]
PHST- 2023/10/23 12:43 [medline]
PHST- 2023/08/08 12:42 [pubmed]
PHST- 2023/08/08 06:53 [entrez]
PHST- 2023/08/16 00:00 [pmc-release]
AID - CTS13606 [pii]
AID - 10.1111/cts.13606 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2023 Oct;16(10):1982-1996. doi: 10.1111/cts.13606. Epub 2023 Aug 
      16.