Effect of Futibatinib on Cardiac Repolarization: Results of a Randomized, Controlled, Double‐Blind, QT/QTc, Phase 1 Study in Healthy Subjects. Issue 3 (20th November 2022)

• Record Type: Journal Article
• Authors: Yamamiya, Ikuo; Lester, Robert; Sonnichsen, Daryl; Mina, Mark; He, Yaohua; Benhadji, Karim A.
• Is Part Of: Clinical pharmacology in drug development. Volume 12:Issue 3(2023)
• Page Start: 304
• Page End: 313
• Publication Date: 2022-11-20
• Subjects: fibroblast growth factor receptor -- futibatinib -- pharmacokinetics -- QTc -- safety; Drugs -- Testing -- Periodicals; Drug development -- Periodicals; Clinical pharmacology -- Periodicals; 615.580724
• DOI: 10.1002/cpdd.1195
• Languages: English
• ISSNs: 2160-7648

Abstract

Abstract: 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.