In this randomized, double-blind, placebo controlled study, the safety of therapeutic (675 mg) and supra-therapeutic (2,700 mg) doses of nitazoxanide was evaluated in accordance with the ICH E14 guidelines. Fifty six (56) subjects participated in four treatment periods and received single doses of nitazoxanide 675 mg, nitazoxanide 2,700 mg, moxifloxacin 400 mg, or placebo. For 675 mg nitazoxanide, the largest change in QTcF from baseline was observed at 12 hours post-dose with a peak value of 1.6 ms (two-sided 90% CI: -0.3, 3.6 ms). The largest negative change in QTcF was observed at 1 hour post-dose (-2.7 ms with two-sided 90% CI: -4.5, -0.8 ms). The largest change in QTcF from baseline for 2,700 mg nitazoxanide was observed at 24 hours post-dose with a peak value of 3.4 ms (two-sided CI: 1.4, 5.4 ms). These findings demonstrate that neither a single dose of 675 mg nor 2,700 mg nitazoxanide prolonged the QT interval in healthy male and female volunteers. The safety results also demonstrate that all four treatments were well-tolerated and the most frequently reported adverse events in the nitazoxanide and moxifloxacin treatment groups were gastrointestinal disorders which were as expected according to the reference safety information.
Keywords: ICH E14 guideline; Thorough QT study; healthy volunteers; moxifloxacin; nitazoxanide.
© 2014, The American College of Clinical Pharmacology.