Thorough QT/QTc Evaluation of the Cardiac Safety of Secnidazole at Therapeutic and Supratherapeutic Doses in Healthy Individuals

SYM‐1219, a novel oral granule formulation of secnidazole, is under development as single‐dose treatment for bacterial vaginosis. This 4‐way, randomized, crossover study evaluated the effects of SYM‐1219 on electrocardiographic (ECG) parameters in 52 healthy subjects. Subjects were administered single doses of SYM‐1219, 2 g (proposed therapeutic dose), 6 g (supratherapeutic dose), placebo, and moxifloxacin (positive control). Serial digital 12‐lead ECGs were recorded pre‐ and postdose; blood samples were taken to determine plasma secnidazole concentrations. A high‐precision QT technique measured ECGs. The primary end point was change from baseline QTcF (∆QTcF); data were analyzed with the objective of excluding QT effects >10 milliseconds at postdosing time points and with exposure‐response analysis. Safety and tolerability were assessed. Single doses of 2 g and 6 g SYM‐1219 did not have a clinically relevant effect on the QTcF interval; an effect >10 milliseconds could be excluded at all postdosing time points. A shallow slope of the exposure‐response relationship was seen (0.058 millisecond per μg/mL; 90%CI 0.042, 0.073); in this model, the effect on QTc can be predicted to be <10 milliseconds up to a secnidazole plasma concentration of ∼125 μg/mL, approximately 3.4‐fold higher than anticipated peak therapeutic plasma levels. The moxifloxacin QT response demonstrated assay sensitivity. The most frequently reported treatment‐emergent adverse events with SYM‐1219 were headache, dizziness, and nausea. This thorough QT study demonstrated that SYM‐1219 in doses and plasma concentrations up to 3‐fold above therapeutically relevant levels does not have a clinically concerning effect on ECG parameters, including the QT interval.