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Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye - a phase 1 clinical study

  • Medical Ophthalmology
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Abstract

Background

N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye.

Methods

First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH4Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days.

Results

In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH4Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH4Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH4Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH4Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH4Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings.

Conclusion

The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.

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Acknowledgements

Patient insurance was provided by the Tiroler Landeskrankenanstalten GmbH (TILAK, Innsbruck, Austria). We thank Jeffrey Nau, MMS, Denis O’Shaughnessy, PhD, and Nathan R.F. Beeley, PhD (Opko Ophthalmics, Miami, USA) for their support.

Clinical trial registration

EudraCT number 2006-002701-32

Animal tests approval no. GZ 66.011/79-BrGT/2003 (Austrian Federal Government of Science and Research).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Innsbruck Medical University, Innsbruck, Austria

    Barbara Teuchner & Eduard Schmid

  2. Department of Medical Statistics, Informatics, and Health Economics, Innsbruck Medical University, Innsbruck, Austria

    Hanno Ulmer

  3. Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020, Innsbruck, Austria

    Waldemar Gottardi & Markus Nagl

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  1. Barbara Teuchner
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  2. Eduard Schmid
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  3. Hanno Ulmer
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  4. Waldemar Gottardi
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  5. Markus Nagl
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Correspondence to Markus Nagl.

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Teuchner, B., Schmid, E., Ulmer, H. et al. Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye - a phase 1 clinical study. Graefes Arch Clin Exp Ophthalmol 246, 1723–1730 (2008). https://doi.org/10.1007/s00417-008-0900-x

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  • DOI: https://doi.org/10.1007/s00417-008-0900-x

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