Tiotropium Respimat® in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials

Abstract Background Tiotropium Respimat® improved lung function in a phase 2 trial in patients with cystic fibrosis (CF). We investigated its efficacy and safety in a phase 3 trial, including a pre-specified pooled analysis of the phase 2 and 3 trials. Methods 12-week, randomized, double-blind, placebo-controlled trial of tiotropium Respimat® 5 μg once daily in patients with CF (N = 463). Results Co-primary efficacy endpoints showed no statistical difference between tiotropium and placebo: percent-predicted forced expiratory volume in 1 s (FEV1 ) area under the curve from 0–4 h (AUC 0–4 h ) (95% CI): 1.64% (0.27,3.55; p = 0.092); percent-predicted trough FEV1 (95% CI) 1.40% (0.50,3.30; p = 0.15). Adverse events were similar between groups. Pooled phase 2/3 trial results showed a treatment difference in favor of tiotropium: percent-predicted FEV1 AUC 0–4 h (95% CI): 2.62% (1.34,3.90). Conclusion Tiotropium was well tolerated in patients with CF; lung function improvements compared with placebo were not statistically significant in the phase 3 trial. Clinical trials These studies are registered with clinical trial identifier numbers NCT00737100 and NCT01179347 NCT00737100 NCT01179347 . These studies are also registered with the EudraCT number: 2008-001156-43 and 2010-019802-17.