Testing Two Different Doses of Tiotropium Respimat® in Cystic Fibrosis: Phase 2 Randomized Trial Results

Background: Tiotropium is a once-daily, long-acting anticholinergic bronchodilator with the potential to alleviate airway obstruction in cystic fibrosis. Our objective was to evaluate the efficacy and safety of 2.5 and 5 mu g once-daily tiotropium delivered via the Respimat Soft Mist Inhaler vs. placebo in people with cystic fibrosis. Methods: This phase 2, 12-week, randomized, double-blind, placebo-controlled parallel-group study of tiotropium Respimat as add-on to usual cystic fibrosis maintenance therapy included people with cystic fibrosis with pre-bronchodilator forced expiratory volume in 1 second (FEV1) >= 25% predicted. Co-primary efficacy end points were change from baseline in percent-predicted FEV1 area under the curve from 0 to 4 hours (FEV1 AUC(0-4h)), and trough FEV1 at the end of week 12. Findings: A total of 510 subjects with cystic fibrosis aged 5-69 years were randomized. Both doses of tiotropium resulted in significant improvement compared with placebo in the co-primary efficacy end points at the end of week 12 (change from baseline in percent-predicted FEV1 AUC(0-4h): 2.5 mu g: 2.94%, 95% confidence interval 1.19-4.70, p = 0.001; 5 mu g: 3.39%, 95% confidence interval 1.67-5.12, p = 0.0001; in percent-predicted trough FEV1: 2.5 mu g: 2.24%, p = 0.2; 5 mu g: 2.22%, p = 0.02). There was a greater benefit with tiotropium 5 vs. 2.5 mu g. No treatment-related adverse events or unexpected safety findings were observed in patients taking tiotropium. Conclusions: Tiotropium significantly improved lung function in people with cystic fibrosis. The improvement was greater with the higher dose than the lower dose, with no difference in adverse events.