QT interval prolongation associated with drug administration is an important consideration in drug development. Patients with COVID-19 are at increased risk for cardiac complications, and QT interval prolongation correlates with higher mortality. This Phase 1 study evaluated the safety, tolerability, pharmacokinetics, and potential effects on QT interval corrected for heart rate (QTc) of a single supratherapeutic intravenous dose of remdesivir (600 mg; 3 times the loading dose [200 mg] of the approved regimen) in healthy participants, as well as the safety of its solubilizing excipient sulfobutylether-β-cyclodextrin. The study included 2 cohorts: a dose-selection cohort (sentinel cohort), followed by a partially blinded, randomized, placebo- and positive-controlled, 3-period, 6-treatment sequence, single-dose crossover cohort (TQT cohort). The clinical endpoints were adverse events (AEs), laboratory abnormalities, plasma pharmacokinetic parameters of remdesivir and its metabolites, ΔΔQTcF (baseline-adjusted, placebo-corrected QT interval corrected for heart rate using the Fridericia formula) at each postdose time point, and the relationship between ΔΔQTcF and plasma concentrations of remdesivir by concentration-QT analysis. Sixty participants completed the study. Plasma pharmacokinetics of remdesivir and its metabolites showed no significant differences between cohorts. Sulfobutylether-β-cyclodextrin was cleared within 24 h, with no pharmacokinetic non-linearities observed. The study found no clinically relevant QTc prolongation from remdesivir at a supratherapeutic dose (ΔΔQTcF < 10 ms). Most AEs were Grade 1 or 2 in severity. No serious AEs or deaths were reported. These findings suggest that a single 600-mg intravenous dose of remdesivir is generally safe and well tolerated and does not lead to QTc prolongation of safety concern.