title: Evaluation of the effect of ruxolitinib on cardiac repolarization: A thorough QT study.
abstract: This was a randomized, four-way crossover study that evaluated the effects of placebo, single doses of ruxolitinib 25 and 200 mg, and a single dose of moxifloxacin 400 mg on heart rate-corrected QT interval in healthy subjects. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on each dosing day; baseline ECGs were taken pre-dose. The primary endpoint was placebo-subtracted change from baseline heart rate-corrected QT (Fridericia formula [ΔΔQTcF]). The ΔΔQTcF for either dose of ruxolitinib ranged from -3.09 to 3.28 milliseconds (1-sided 95% confidence interval of 0.06-6.62 milliseconds). The ΔΔQTcF for moxifloxacin (lower confidence interval) was significantly >5 milliseconds at 1, 2, and 3 hours post-dose. Individual QTcF >450 milliseconds and QTcF from baseline >30 milliseconds following ruxolitinib were similar to placebo. Based on the International Conference on Harmonization E14 guidance, the study results were considered negative for QTc prolongation. In conclusion, ruxolitinib did not have a clinically significant effect on QT interval.
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Naresh
authors.initials: N
authors.lastname: Punwani
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Swamy
authors.initials: S
authors.lastname: Yeleswaram
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Bowman
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Maxim
authors.initials: M
authors.lastname: Soloviev
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: William
authors.initials: W
authors.lastname: Williams
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects; D064368:Healthy Volunteers; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D000075242:Janus Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D009570:Nitriles; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011743:Pyrimidines; D018570:Risk Assessment; D013997:Time Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000075242:Janus Kinase Inhibitors; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D000077266:Moxifloxacin
keywords: JAK inhibitor; QT prolongation; clinical pharmacology; ruxolitinib