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

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.