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Analyzing the relationship of QT interval and exposure to Nitazoxanide, a prospective candidate for influenza antiviral therapy—A formal TQT study

Authors

  • Jörg Täubel MD, FFPM,

    Corresponding author
    1. Richmond Pharmacology Ltd., St George's University of London, Cranmer Terrace, London, UK
    2. Department of Cardiological Sciences, St George's University of London, Cranmer Terrace, London, UK
    • Corresponding Author:

      Dr Jörg Täubel, Richmond Pharmacology Ltd, St George's University of London, Cranmer Terrace, Tooting, London, SW17 0RE, UK

      Email: j.taubel@richmondpharmacology.com

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  • Ulrike Lorch MD, FRCA, FFPM,

    1. Richmond Pharmacology Ltd., St George's University of London, Cranmer Terrace, London, UK
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  • Jean-François Rossignol PhD, FRSC, MD, FRCPath, FFPM,

    1. The Romark Institute for Medical Research, 3000 Bayport Drive, Suite 200, Tampa, FL, USA
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  • Georg Ferber PhD,

    1. Richmond Pharmacology Ltd., St George's University of London, Cranmer Terrace, London, UK
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  • A. John Camm QHP, MD, FRCP, FESC, FACC

    1. Department of Cardiological Sciences, St George's University of London, Cranmer Terrace, London, UK
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  • Results of this study were presented in part in poster form at the Pharmacology 2013 (London, UK; 17–19 December 2013).

Abstract

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.

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