PMID- 36404525
OWN - NLM
STAT- MEDLINE
DCOM- 20230302
LR  - 20230321
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 12
IP  - 3
DP  - 2023 Mar
TI  - Effect of Futibatinib on Cardiac Repolarization: Results of a Randomized, 
      Controlled, Double-Blind, QT/QTc, Phase 1 Study in Healthy Subjects.
PG  - 304-313
LID - 10.1002/cpdd.1195 [doi]
AB  - Futibatinib, a fibroblast growth factor receptor (FGFR) 1-4 inhibitor, is being 
      investigated for FGFR-aberrant tumors. A 4-period, crossover, phase 1 thorough 
      QT/QTc study compared effects on Fridericia heart rate-corrected QT (QTcF) 
      interval of single doses of futibatinib 20 and 80 mg (therapeutic and 
      supratherapeutic doses, respectively), placebo, and moxifloxacin (positive 
      control) in healthy subjects. The study objective was to assess the time-matched 
      difference in change from baseline in QTcF (ddQTcF) between futibatinib and 
      placebo. In addition, changes from baseline in QTcF and other electrocardiogram 
      (ECG) parameters, pharmacokinetics, ECG morphology, and safety were assessed. 
      Forty-eight subjects were randomized. ddQTcF upper limits of 2-sided 90%CIs 
      remained <10 milliseconds (clinical threshold) for both futibatinib doses at all 
      time points (range, 2.0-4.5 milliseconds). Assay sensitivity was demonstrated by 
      lower limits of 2-sided 97.5%CIs of the dQTcF difference between moxifloxacin and 
      placebo of >5 milliseconds. Futibatinib exposure increased in a dose-dependent 
      manner, and no significant relationship was detected between plasma futibatinib 
      concentration and ddQTcF. There were no significant effects on heart rate, other 
      ECG parameters, or ECG morphology. No serious adverse events occurred. 
      Futibatinib did not prolong QTcF or affect other cardiac measures at therapeutic 
      or supratherapeutic doses.
CI  - (c) 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley 
      Periodicals LLC on behalf of American College of Clinical Pharmacology.
FAU - Yamamiya, Ikuo
AU  - Yamamiya I
AD  - Taiho Oncology, Inc., Princeton, New Jersey, USA.
FAU - Lester, Robert
AU  - Lester R
AD  - Celerion, Tempe, Arizona, USA.
FAU - Sonnichsen, Daryl
AU  - Sonnichsen D
AD  - Sonnichsen Pharmaceutical Associates, LLC, Collegeville, Pennsylvania, USA.
FAU - Mina, Mark
AU  - Mina M
AD  - Taiho Oncology, Inc., Princeton, New Jersey, USA.
FAU - He, Yaohua
AU  - He Y
AD  - Taiho Oncology, Inc., Princeton, New Jersey, USA.
FAU - Benhadji, Karim A
AU  - Benhadji KA
AD  - Taiho Oncology, Inc., Princeton, New Jersey, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221120
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - U188XYD42P (Moxifloxacin)
RN  - 4B93MGE4AL (futibatinib)
RN  - 0 (Fluoroquinolones)
SB  - IM
MH  - Humans
MH  - Moxifloxacin/adverse effects
MH  - *Fluoroquinolones/adverse effects
MH  - Healthy Volunteers
MH  - *Heart
OTO - NOTNLM
OT  - QTc
OT  - fibroblast growth factor receptor
OT  - futibatinib
OT  - pharmacokinetics
OT  - safety
EDAT- 2022/11/22 06:00
MHDA- 2023/03/03 06:00
CRDT- 2022/11/21 01:19
PHST- 2022/07/27 00:00 [received]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2022/11/21 01:19 [entrez]
AID - 10.1002/cpdd.1195 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2023 Mar;12(3):304-313. doi: 10.1002/cpdd.1195. Epub 
      2022 Nov 20.