Key result
Single-dose ruxolitinib shows no clinically significant effect on the QT interval.
Why the study?
The effect of ruxolitinib on cardiac repolarization and QT interval prolongation needed evaluation in healthy subjects.
Does single-dose ruxolitinib prolong the heart rate-corrected QT interval in healthy subjects?
RCT
Four-way crossover
Does single-dose ruxolitinib prolong the heart rate-corrected QT interval in healthy subjects?
Effect estimate: ΔΔQTcF -3.09 to 3.28 milliseconds (95% CI 0.06-6.62)
Single doses of ruxolitinib up to 200 mg do not cause clinically significant QTc prolongation in healthy subjects.
Ruxolitinib shows no QTc prolongation; confirms cardiac safety and supports use without routine ECG monitoring in indicated populations.
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.
No takes yet. Share an insight, caveat, or question.
Punwani et al. (2013) conducted an RCT in Healthy. Ruxolitinib vs. Placebo was evaluated on Placebo-subtracted change from baseline heart rate-corrected QT (Fridericia formula [ΔΔQTcF]) (ΔΔQTcF -3.09 to 3.28 milliseconds, 95% CI 0.06-6.62). Single doses of ruxolitinib 25 and 200 mg did not have a clinically significant effect on the QT interval, with ΔΔQTcF ranging from -3.09 to 3.28 milliseconds (95% CI 0.06-6.62).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: