Fractional exhaled nitric oxide in clinical trials: an overview

Designing clinical trials in asthma it is crucial to find the perfect primary endpoint for showing bioequivalence, especially when the investigational medicinal product is not a bronchodilator, but a substance, which suppresses the inflammatory process, e.g. inhalative corticosteroids (ICS). In the past, lung function parameters were used as the primary endpoint, which entails a long study duration and hundreds of patients. The measurement of fractional exhaled nitric oxide (FeNO) is established as a non-invasive marker for eosinophilic inflammation, and several guidelines focus on that diagnosis. FeNO is a surrogate measure of eosinophilic inflammation and at the same time, eosinophilic airway inflammation is usually steroid responsive. Thus, FeNO should be a part of the clinical management of asthma in ambulatory settings in conjunction with other conventional methods of asthma assessment. Furthermore, FeNO should be used to determine the presence or absence of eosinophilic airway inflammation, to determine the likelihood of steroid responsiveness, to measure response to steroid therapy, and level of inflammation control. In addition, FeNO is a useful tool to monitor patient ICS treatment adherence and allergen exposure. FeNO may be used to predict steroid responsiveness and as a measure to determine the optimal treatment of airway inflammation. FeNO has all characteristics of a good marker for bioequivalence measurements in the market approval process of generic ICS products. With a reliable study design in terms of patient population, concomitant medication, equipment and other factors, which can influence the measurement, efficient clinical trials can be performed, with a relatively short treatment time of 2-4 weeks and 50-100 patients.