Tolerability of inhaled N-chlorotaurine in humans

In this project for the call Clinical Research, the tolerability of inhaled N-chlorotaurine (NCT), an endogenous antiseptic, will be investigated for the first time in humans in a phase I clinical study. NCT is very well tolerated by human tissue of different body regions. Therapeutical efficacy has been proved in phase 2 clinical studies in purulently coated crural ulcers, otitis externa, and conjunctivitis so far. In two studies in pigs and one study in mice, inhalation of 1% NCT proved to be very well tolerated, as well as in a pilot study with three humans. Therefore, we hypothesize that inhaled NCT is well tolerated in humans. The aim of the proposed study is the investigation and demonstration of the tolerability of repeatedly inhaled 1% NCT in aqueous solution in humans. Study design: The study will be performed double-blind and randomized with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). Two Austrian centers will be involved, the hospitals Natters belonging to the Innsbruck University Hospital and Vöcklabruck in Upper Austria. Study population: The study will be performed in healthy, full age volunteers. In total, 24 subjects will be tested, 12 in each center. 12 subjects will be treated with NCT, 12 with placebo, at which exactly the half of the test and control group will be treated in each center. Study medication: The test solution consists of 1% NCT in aqueous solution, the control solution of 0.9% NaCl. The single filling dose is 3 ml, which will be inhaled over a period of 10 min using the AKITA JET inhalation system. The inhalation system is preset via a smart card for delivering an amount of 1.2 ml to the mouthpiece and approximately 1 ml to the lungs of the subjects. Number of treatments: One inhalation will be performed by preset number of breaths over 10 min on every day on 5 consecutive days. Therefore, the total number of inhalations is 5. Evaluation: Primary criterion of evaluation is the forced expiratory volume in the first second (FEV1), which should not be reduced by 10% compared to the baseline and by 20% compared to 0.9% NaCl (thresholds of statistical significance). Secondary criteria are subjective sensations, further lung function parameters such as airway resistance, physical examination, and blood analyses (gases, electrolytes, organ function values, pharmacokinetic parameters taurine and cystine). We attach great importance to the study since it is fundamental for the investigation of inhaled NCT for treatment of bronchopulmonary diseases, where microorganisms play a role. The availability of a well tolerated and effective inhaled antiseptic with antiinflammatory properties would be a significant progress, in particular for chronic pulmonary diseases, such as COPD or cystic fibrosis.

The tolerability of inhaled N-chlorotaurine (NCT) in humans was proved in this clinical phase I study. NCT is an antiinfective molecule produced by the human white blood cells during infections to combat bacteria, fungi and viruses. It can be synthesized chemically, too, and used for local treatment if infections or abscesses. In contrast to antibiotics, no resistance development occurs, and multiresistant microorganisms can be treated with NCT. As a body-own mild oxidizing agent, NCT is very well tolerated by human tissue in different body sites, including highly sensitive ones. Methods: This study was performed double-blind with a parallel test group (1% NCT) and control group (0.9% NaCl as placebo). Two centers were involved, the hospitals Natters and Vöcklabruck. Healthy, full age volunteers were included, 12 in each center. 12 subjects were treated with NCT, 12 with placebo, exactly the half of each group in each center. The single dose was 1.2 ml, inhaled over a period of 10 min using an Akita-Jet nebulizer. One inhalation was done on every day on 5 consecutive days.Results: All included 15 females and 9 males completed the treatment and the control examinations according to the study protocol. Lung function remained unchanged and constant during the treatment and in control examinations 1 week and 3 months after the treatment. The same was true for all other objective parameters. Subjective mild sensations were chlorine taste, occasional scratching and itching in the throat. There were no toxic effects and no diffusion of the substance into the blood. Conclusions: Inhaled NCT is safe and very well tolerated as in other applications of different body regions. Side effects are mild, topical and transitory.Possible applications: The successful phase I study in healthy persons paves the way for further clinical studies on tolerability and efficacy in patients. Promising indications are for instance chronic bronchitis and viral bronchitis, which involve millions of people, and mucoviscidosis.