PMID- 35182043
OWN - NLM
STAT- MEDLINE
DCOM- 20220404
LR  - 20220729
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Print)
IS  - 2160-763X (Linking)
VI  - 11
IP  - 4
DP  - 2022 Apr
TI  - Lack of Electrocardiographic Effects of Deucravacitinib in Healthy Subjects.
PG  - 442-453
LID - 10.1002/cpdd.1056 [doi]
AB  - Deucravacitinib is a novel, oral, selective inhibitor of the intracellular 
      signaling kinase tyrosine kinase 2. This phase 1, randomized, partially 
      double-blind, 4-period crossover study in healthy adults was conducted to 
      determine whether deucravacitinib 12 mg (therapeutic dose) or 36 mg 
      (supratherapeutic dose) had a clinically relevant effect on the corrected QT 
      interval and other electrocardiographic (ECG) parameters. Subjects received 1 of 
      4 sequences of placebo, deucravacitinib 12 mg, deucravacitinib 36 mg, and 
      moxifloxacin 400 mg (positive control) in a randomized crossover fashion. The 
      placebo-corrected change from baseline for the QT interval corrected for heart 
      rate using the Fridericia method (QTcF), ECG parameters, and safety measures were 
      evaluated. A clinically meaningful QTcF prolongation of >10 milliseconds was not 
      found for deucravacitinib at tested doses. Assay sensitivity was demonstrated by 
      the observation of known QT effects of moxifloxacin in the study. Deucravacitinib 
      had no clinically relevant effect on other parameters and was generally well 
      tolerated. The majority of adverse events (AEs) were mild, and all AEs resolved 
      by study's end. Three treatment-related serious AEs of pharyngitis, cellulitis, 
      and lymphadenopathy occurred in 1 subject following administration of 
      deucravacitinib 12 mg, but resolved by end of study. This study demonstrated that 
      a single oral dose of deucravacitinib 12 or 36 mg did not produce a clinically 
      relevant effect on the corrected QT interval or other measured ECG parameters in 
      healthy adults.
CI  - (c) 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley 
      Periodicals LLC on behalf of American College of Clinical Pharmacology.
FAU - Chimalakonda, Anjaneya
AU  - Chimalakonda A
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Singhal, Shalabh
AU  - Singhal S
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Darbenzio, Raymond
AU  - Darbenzio R
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Dockens, Randy
AU  - Dockens R
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Marchisin, David
AU  - Marchisin D
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Banerjee, Subhashis
AU  - Banerjee S
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Girgis, Ihab G
AU  - Girgis IG
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Throup, John
AU  - Throup J
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - He, Bing
AU  - He B
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Aras, Urvi
AU  - Aras U
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
FAU - Murthy, Bindu
AU  - Murthy B
AD  - Bristol Myers Squibb, Princeton, New Jersey, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220219
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Heterocyclic Compounds)
RN  - N0A21N6RAU (deucravacitinib)
RN  - U188XYD42P (Moxifloxacin)
SB  - IM
MH  - Adult
MH  - Cross-Over Studies
MH  - *Electrocardiography
MH  - Healthy Volunteers
MH  - Heterocyclic Compounds/adverse effects
MH  - Humans
MH  - Moxifloxacin/adverse effects
PMC - PMC9306920
OTO - NOTNLM
OT  - cardiovascular
OT  - clinical pharmacology
OT  - dermatology
OT  - drug metabolism
OT  - electrocardiography
OT  - pharmacokinetics
COIS- The authors are employees of and shareholders in Bristol Myers Squibb.
EDAT- 2022/02/20 06:00
MHDA- 2022/04/05 06:00
PMCR- 2022/07/22
CRDT- 2022/02/19 05:33
PHST- 2021/05/03 00:00 [received]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2022/02/20 06:00 [pubmed]
PHST- 2022/04/05 06:00 [medline]
PHST- 2022/02/19 05:33 [entrez]
PHST- 2022/07/22 00:00 [pmc-release]
AID - CPDD1056 [pii]
AID - 10.1002/cpdd.1056 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2022 Apr;11(4):442-453. doi: 10.1002/cpdd.1056. Epub 
      2022 Feb 19.