Safety and tolerability of the NE inhibitor BAY 85-8501 in patients with non-CF bronchiectasis

Abstract

<b>Background:</b> Inhibition of excessive neutrophil elastase (NE) might represent a therapeutic approach in neutrophilic airway diseases such as non-cystic fibrosis bronchiectasis (NCFB). <b>Methods:</b> We conducted a multicenter, phase IIa, randomized, double-blind, placebo-controlled, parallel-group study in patients with NCFB. Primary endpoint was safety and tolerability of 28-day oral administration of BAY 85-8501 (1.0 mg OD). Secondary objectives included lung function, biomarkers of inflammation and tissue damage, and health status (ClinicalTrials.gov Identifier: NCT01818544). <b>Results:</b> 94 patients (mean age, 66 years, 53% male) were randomized to treatment. 45 patients received BAY 85-8501. A total of 67 patients reported treatment-emergent adverse events (TEAEs); 31 patients with BAY 85-8501and 36 patients with placebo. The most frequently reported TEAEs were headache, nasopharyngitis, and cough with no difference between groups. 3 patients in the BAY 85-8501 treatment group and 1 patient in the placebo group had a serious TEAE, all not assessed to be related to study treatment. There were no clinically relevant changes in blood pressure, heart rate, ECG, and blood-laboratory parameters. Compared to placebo there were no significant changes in lung function, health status, 24 hour sputum weight, NE activity and concentration, and other biomarkers including urine desmosine. <b>Conclusion:</b> BAY 85-8501 1.0 mg OD was generally safe and well tolerated over 28 days in patients with non-CF BE. Further studies need to show long-term safety and potential efficacy of BAY 85-8501 in patients with non-CF BE.