PMID- 36325947
OWN - NLM
STAT- MEDLINE
DCOM- 20230215
LR  - 20231213
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 16
IP  - 1
DP  - 2023 Jan
TI  - First-in-human study of deucravacitinib: A selective, potent, allosteric 
      small-molecule inhibitor of tyrosine kinase 2.
PG  - 151-164
LID - 10.1111/cts.13435 [doi]
AB  - This randomized, double-blind, single- and multiple-ascending dose study assessed 
      the pharmacokinetics (PKs), pharmacodynamics, and safety of deucravacitinib 
      (Sotyktu), a selective and potent small-molecule inhibitor of tyrosine kinase 2, 
      in 100 (75 active, 25 placebo) healthy volunteers (NCT02534636). Deucravacitinib 
      was rapidly absorbed, with a half-life of 8-15 h, and 1.4-1.9-fold accumulation 
      after multiple dosing. Deucravacitinib inhibited interleukin 
      (IL)-12/IL-18-induced interferon (IFN)gamma production ex vivo in a dose- and 
      concentration-dependent manner. Following in vivo challenge with IFNalpha-2a, 
      deucravacitinib demonstrated dose-dependent inhibition of lymphocyte count 
      decreases and expression of 53 IFN-regulated genes. There were no serious adverse 
      events (AEs); the overall frequency of AEs was similar in the deucravacitinib 
      (64%) and placebo (68%) groups. In this first-in-human study, deucravacitinib 
      inhibited IL-12/IL-23 and type I IFN pathways in healthy volunteers, with 
      favorable PK and safety profiles. Deucravacitinib is a promising therapeutic 
      option for immune-mediated diseases, including Crohn's disease, psoriasis, 
      psoriatic arthritis, and systemic lupus erythematosus.
CI  - (c) 2022 Bristol Myers Squibb. Clinical and Translational Science published by 
      Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Catlett, Ian M
AU  - Catlett IM
AUID- ORCID: 0000-0001-6220-2626
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Aras, Urvi
AU  - Aras U
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Hansen, Lars
AU  - Hansen L
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Liu, Yali
AU  - Liu Y
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Bei, Di
AU  - Bei D
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Girgis, Ihab G
AU  - Girgis IG
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Murthy, Bindu
AU  - Murthy B
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02534636
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221122
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - N0A21N6RAU (deucravacitinib)
RN  - EC 2.7.10.2 (TYK2 Kinase)
RN  - 0 (Tyrosine Kinase Inhibitors)
SB  - IM
MH  - Humans
MH  - Area Under Curve
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - *TYK2 Kinase/antagonists & inhibitors
MH  - *Tyrosine Kinase Inhibitors/pharmacology/therapeutic use
MH  - Autoimmune Diseases/drug therapy
PMC - PMC9841305
COIS- I.M.C., U.A., I.G.G., and B.M. are employees of Bristol Myers Squibb and receive 
      salaries and stock commensurate with employment. L.H., Y.L., and D.B. were 
      employees of Bristol Myers Squibb at the time this research was conducted.
EDAT- 2022/11/04 06:00
MHDA- 2023/01/18 06:00
PMCR- 2022/11/22
CRDT- 2022/11/03 05:13
PHST- 2022/09/13 00:00 [revised]
PHST- 2022/04/08 00:00 [received]
PHST- 2022/09/19 00:00 [accepted]
PHST- 2022/11/04 06:00 [pubmed]
PHST- 2023/01/18 06:00 [medline]
PHST- 2022/11/03 05:13 [entrez]
PHST- 2022/11/22 00:00 [pmc-release]
AID - CTS13435 [pii]
AID - 10.1111/cts.13435 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2023 Jan;16(1):151-164. doi: 10.1111/cts.13435. Epub 2022 Nov 
      22.