Gadopiclenol does not prolong QTc interval in healthy individuals
A new gadolinium-based contrast agent, gadopiclenol, at clinical and supraclinical doses does not result in prolonged QT interval and has an acceptable safety profile among healthy volunteers, a recent study has found.
“The positive slope of the QTc prolongation vs concentration relationship suggests that hyperosmolarity could be associated with QTc prolongation,” the investigators said. “However, the amplitude of this effects is unlikely to be associated with proarrhythmia.”
This single-centre, randomized, double-blind, placebo- and positive-controlled, four-way crossover study included 48 healthy male and female individuals who received single intravenous (IV) administration of gadopiclenol at a clinical dose of 0.1 mmol kg-1 (standard for current gadolinium-based contrast agents), a supraclinical dose of 0.3 mmol kg-1, placebo, and a single oral dose of moxifloxacin 400 mg.
The biggest time‐matched, placebo‐corrected, mean change from‐baseline in QTcF (ΔΔQTcF) was seen 3 hours after administration of 0.1 mmol kg−1 gadopiclenol (2.39 ms, 90 percent confidence interval [CI], 0.35–4.43) and 5 minutes after administration of 0.3 mmol kg−1 (4.81 ms, 90 percent CI, 2.84–6.78).
The upper limit of the 90 percent CI was under the threshold of 10 ms, which showed no substantial effect of gadopiclenol on QTc interval. The lower limit of the 90 percent CI of ΔΔQTcF from 1.5–4 hours postdose moxifloxacin exceeded 5 ms, indicating assay sensitivity.
A positive slope was observed, but the concentration–response analysis estimated that the values of ΔΔQTcF at the maximal concentration of gadopiclenol at 0.1 and 0.3 mmol kg-1 were 0.41 and 2.23 ms, respectively, with the upper limit of the 90 percent CI not exceeding 10 ms.
There were no serious or adverse events (AEs) or treatment discontinuations due to AEs reported, according to the investigators.