Key result
Single intravenous doses of palonosetron up to 2.25 mg did not prolong the QTc interval, with the upper bound of the 95% confidence interval for ΔΔ QTcI remaining <10 ms at all time points.
Why the study?
Does intravenous palonosetron prolong the QTc interval in healthy volunteers?
RCT (n=221)
Double-blind
Randomized
No
Does intravenous palonosetron prolong the QTc interval in healthy volunteers?
Single intravenous doses of palonosetron up to 2.25 mg do not prolong the QTc interval in healthy volunteers, confirming its cardiac safety profile regarding repolarization.
Palonosetron up to 2.25 mg IV requires no QTc monitoring; confirms cardiac safety in this dedicated RCT.
PURPOSE: The use of serotonin type 3 (5-HT3) receptor antagonists (RAs) in the prevention of nausea and vomiting caused by emetogenic chemotherapy is part of a comprehensive management strategy for patients undergoing chemotherapy. Electrocardiographic effects have been reported in patients after intravenous administration of 5-HT3 RAs. The present study investigated the electrocardiogram (ECG) profile of the 5-HT3 RA palonosetron following International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) E14 Guidelines. METHODS: A total of 221 healthy subjects (101 females, 120 males) were randomized in this phase I, double-blind, double-dummy, parallel group study and assigned to one of five treatments: placebo, palonosetron (0.25, 0.75, or 2.25 mg), or moxifloxacin (400 mg). ECGs were recorded for 24 h pre-dosing until 48 h post-dose. The primary endpoint was the placebo time-matched and baseline-subtracted individual QTc interval prolongation (ΔΔQTcI). RESULTS: The QTc interval was not prolonged after administration of palonosetron (ΔΔQTcI upper confidence interval was <10 ms for all time points in all palonosetron treatment groups). Assay sensitivity was confirmed with the expected change in the QTc interval after administration of the positive control moxifloxacin. CONCLUSIONS: Palonosetron, even at supratherapeutic doses, has no effect on cardiac repolarization as measured by the QTc interval in a validated controlled clinical trial.
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Morganroth et al. (2015) conducted an RCT in Healthy volunteers (n=221). Palonosetron IV vs. Placebo (and Moxifloxacin 400 mg positive control) was evaluated on Placebo time-matched and baseline-subtracted individual QTc interval prolongation (ΔΔ QTcI). Single intravenous doses of palonosetron up to 2.25 mg did not prolong the QTc interval, with the upper bound of the 95% confidence interval for ΔΔ QTcI remaining <10 ms at all time points.
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