Randomized study of the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval in healthy subjects.

AIM: We investigated the effect of gadopiclenol, a new gadolinium-based contrast agent, on the QTc interval at clinical and supra-clinical dose, considering the relative hyperosmolarity of this product. METHODS: This was a single centre, randomized, double-blind, placebo- and positive-controlled, four-way crossover study. Forty-eight healthy male and female subjects were included to receive single intravenous (i.v.) administrations of gadopiclenol at the clinical dose of 0.1 mmolkg(-1) , standard for current gadolinium-based contrast agents, the supra-clinical dose of 0.3 mmolkg(-1) , placebo and a single oral dose of 400 mg moxifloxacin. RESULTS: The largest time-matched placebo-corrected, mean change from-baseline in QTcF (DeltaDeltaQTcF) was observed 3 h after administration of 0.1 mmolkg(-1) gadopiclenol (2.39 ms, 90% confidence interval (CI): 0.35, 4.43 ms) and 5 min after administration of 0.3 mmolkg(-1) (4.81 ms, 90%CI: 2.84; 6.78 ms). The upper limit of the 90% CI was under the threshold of 10 ms, demonstrating no significant effect of gadopiclenol on QTc interval. From 1.5 to 4 h post-dose moxifloxacin, the lower limit of the 90% CI of DeltaDeltaQTcF exceeded 5 ms demonstrating assay sensitivity. Although there was a positive slope, the concentration-response analysis estimated that the values of DeltaDeltaQTcF at the maximal concentration of gadopiclenol at 0.1 and 0.3 mmolkg-1 were 0.41 and 2.23 ms, respectively, with the upper limit of the 90% CI not exceeding 10 ms. No serious or severe adverse events or treatment discontinuations due to adverse events were reported. CONCLUSION: This thorough QT/QTc study demonstrated that gadopiclenol did not prolong the QT interval at clinical and supra-clinical doses and was well tolerated in healthy volunteers. The positive slope of the QTc prolongation vs. concentration relationship suggests that hyperosmolarity could be associated with QTc prolongation. However, the amplitude of this effects is unlikely to be associated with proarrhythmia.