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Evaluation of the effect of ruxolitinib on cardiac repolarization: A thorough QT study
Author(s) -
Punwani Naresh,
Yeleswaram Swamy,
Chen Xuejun,
Bowman Jill,
Soloviev Maxim,
Williams William
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.90
Subject(s) - medicine , moxifloxacin , qt interval , ruxolitinib , placebo , cardiology , confidence interval , dosing , heart rate , clinical endpoint , anesthesia , clinical trial , antibiotics , blood pressure , bone marrow , alternative medicine , pathology , microbiology and biotechnology , myelofibrosis , biology
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.