PMID- 34366847
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210810
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - First-in-Human, Double-Blind, Randomized, Placebo-Controlled Trial of TQ-F3083, a 
      New Dipeptidyl Peptidase-4 Inhibitor, in Healthy Chinese Adults.
PG  - 689523
LID - 10.3389/fphar.2021.689523 [doi]
LID - 689523
AB  - Background: As a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, TQ-F3083 
      represents a promising new drug for type 2 diabetes mellitus (T2DM). This phase 
      I, first-in-human study evaluated the tolerability, pharmacokinetics, and 
      pharmacodynamics of TQ-F3083 in healthy Chinese adults. Methods: Sixty healthy 
      participants total were enrolled in the single-ascending dose, multiple-dose, and 
      food-effect studies. Safety endpoints included adverse events (AEs), vital signs, 
      12-lead electrocardiogram, abdominal ultrasound, chest X-ray, physical 
      examination, and clinical laboratory tests. Blood, urine, and feces samples were 
      collected for pharmacokinetic analyses. Pharmacodynamic parameters were evaluated 
      based on DPP-4 activity and the active glucagon-like peptide-1 concentration. 
      Results: In total, 22 treatment-related AEs, mostly grade 1 or 2, were reported 
      in 14 individuals. No deaths, serious AEs, or grade >/=4 AEs occurred, and no 
      dose-dependent AEs were demonstrated. For pharmacokinetic characteristics, dose 
      linearity was analyzed using power model. The slopes (90% CIs) were 1.08 
      (1.02-1.13) and 1.05 (0.99-1.11) for AUC(0-t) and AUC(0-infinity), suggesting liner 
      pharmacokinetic characteristic after oral dose TQ-F3083 from 2 to 160 mg. The 
      accumulation factor was 1.39 after multiple dose for 7 days. Decreased plasma 
      exposure (84.87% decrease in C(max), 49.23% in AUC(0-t), and 47.77% in AUC(0-infinity)) 
      was observed with administration after a high-fat and high-calorie standardized 
      breakfast. The 0-72 h TQ-F3083 excretion recovery percentages were 7.84% in urine 
      and 5.76% in feces. Over 80% DPP-4 inhibition for 24 h was observed in the 
      20-160 mg cohorts, and the model-estimated 50% effective concentration was 
      1.10 ng/ml. The concentration of active glucagon-like peptide-1 increased after 
      TQ-F3083 administration, but no obvious dose dependency was observed. Conclusion: 
      TQ-F3083 was well tolerated in healthy Chinese adults, and the pharmacokinetic 
      and pharmacodynamic characteristics support further evaluation of TQ-F3083 in a 
      trial in T2DM patients.
CI  - Copyright (c) 2021 Liu, Zhu, Zhang, Wei, Yang, Xu, Huo, Li and Ding.
FAU - Liu, Jingrui
AU  - Liu J
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhu, Xiaoxue
AU  - Zhu X
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Wei, Haijing
AU  - Wei H
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Yang, Deming
AU  - Yang D
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Xu, Zhongnan
AU  - Xu Z
AD  - Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
FAU - Huo, Dandan
AU  - Huo D
AD  - Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Nanjing, China.
FAU - Li, Xiaojiao
AU  - Li X
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
FAU - Ding, Yanhua
AU  - Ding Y
AD  - Phase I Clinical Trial Unit, The First Hospital of Jilin University, Changchun, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210722
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8339258
OTO - NOTNLM
OT  - TQ-F3083
OT  - pharmacodynamics
OT  - pharmacokinetics
OT  - phase I
OT  - type 2 diabetes
COIS- Authors ZX and DH are employees of Chia Tai Tianqing Pharmaceutical Group 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- 2021/08/10 06:00
MHDA- 2021/08/10 06:01
PMCR- 2021/07/22
CRDT- 2021/08/09 06:29
PHST- 2021/04/01 00:00 [received]
PHST- 2021/06/24 00:00 [accepted]
PHST- 2021/08/09 06:29 [entrez]
PHST- 2021/08/10 06:00 [pubmed]
PHST- 2021/08/10 06:01 [medline]
PHST- 2021/07/22 00:00 [pmc-release]
AID - 689523 [pii]
AID - 10.3389/fphar.2021.689523 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Jul 22;12:689523. doi: 10.3389/fphar.2021.689523. 
      eCollection 2021.