PMID- 33331206
OWN - NLM
STAT- MEDLINE
DCOM- 20210303
LR  - 20210326
IS  - 1366-5928 (Electronic)
IS  - 0049-8254 (Linking)
VI  - 51
IP  - 3
DP  - 2021 Mar
TI  - Tolerability, safety, pharmacokinetics and pharmacodynamics of SHR0534, a potent 
      G protein-coupled receptor 40 (GPR40) agonist, at single- and multiple-ascending 
      oral doses in healthy Chinese subjects.
PG  - 297-306
LID - 10.1080/00498254.2020.1864510 [doi]
AB  - SHR0534 is being developed for type-2 diabetes mellitus. Herein the tolerability, 
      safety, pharmacokinetics and pharmacodynamics of SHR0534 in healthy Chinese 
      subjects were assessed in a phase-I, randomized, double-blind, 
      placebo-controlled, single- and multiple-ascending dose study. Forty subjects 
      were randomized 4:1 to receive SHR0534 at the dose of 10, 25, 50 or 100 mg, or 
      placebo, and another eleven subjects were allocated to either the 5 mg group or 
      the placebo group at an 8:3 ratio. All subjects received a single dose on day 1, 
      followed by a 9-day washout and once-daily administrations for 14 consecutive 
      days. Serial samples were collected, and vital signs, electrocardiograms, 
      laboratory tests, urinalysis and adverse events (AEs) were recorded. All doses of 
      SHR0534 were safe and well tolerated with infrequent, generally mild-to-moderate 
      AEs and no serious AEs in the study. SHR0534 was absorbed with a T (max) of 
      approximately 4 hours, and systemic exposure increased with dose. Accumulation 
      was minimal (2- to 3-fold) and steady state was reached after seven days of 
      dosing. For pharmacodynamics, no significant hypoglycaemic effects were seen in 
      healthy adults. Good pharmacokinetics and safety were demonstrated but no obvious 
      effect was found.
FAU - Zhao, Yuqing
AU  - Zhao Y
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Xie, Lijun
AU  - Xie L
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Ou, Ning
AU  - Ou N
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Wu, Jie
AU  - Wu J
AD  - Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, China.
FAU - Zhang, Hongwen
AU  - Zhang H
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Zhou, Sufeng
AU  - Zhou S
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Liu, Yun
AU  - Liu Y
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Chen, Juan
AU  - Chen J
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Wang, Lu
AU  - Wang L
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Wang, Libin
AU  - Wang L
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
FAU - Wang, Jingjing
AU  - Wang J
AD  - Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, China.
FAU - Shao, Feng
AU  - Shao F
AD  - Phase I Clinical Trial Unit, Jiangsu Province Hospital and the First Affiliated 
      Hospital with Nanjing Medical University, Nanjing, China.
AD  - Pharmacy College, Nanjing Medical University, Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20201228
PL  - England
TA  - Xenobiotica
JT  - Xenobiotica; the fate of foreign compounds in biological systems
JID - 1306665
RN  - 0 (FFAR1 protein, human)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Organic Chemicals)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SHR0534)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - China
MH  - Diabetes Mellitus, Type 2
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage/*pharmacokinetics/pharmacology
MH  - Metabolic Clearance Rate
MH  - Organic Chemicals/administration & dosage/*pharmacokinetics/pharmacology
MH  - Receptors, G-Protein-Coupled/*agonists
OTO - NOTNLM
OT  - GPR40 agonists
OT  - SHR0534
OT  - diabetes mellitus
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - safety and tolerability
EDAT- 2020/12/18 06:00
MHDA- 2021/03/04 06:00
CRDT- 2020/12/17 08:39
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/03/04 06:00 [medline]
PHST- 2020/12/17 08:39 [entrez]
AID - 10.1080/00498254.2020.1864510 [doi]
PST - ppublish
SO  - Xenobiotica. 2021 Mar;51(3):297-306. doi: 10.1080/00498254.2020.1864510. Epub 
      2020 Dec 28.