Felix Ratjen1, Paul Koker2, David E Geller3, Berengere Langellier-Cocteaux4, Florence Le Maulf4, Sabine Kattenbeck5, Petra Moroni-Zentgraf6, J Stuart Elborn7. 1. Division of Respiratory Medicine, Department of Pediatrics, and Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, and University of Toronto, Toronto, Ontario, Canada. Electronic address: felix.ratjen@sickkids.ca. 2. Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, United States. 3. Florida State University College of Medicine, Orlando, FL, United States. 4. Boehringer Ingelheim France SAS, Reims, France. 5. Boehringer Ingelheim GmbH, Ingelheim, Germany. 6. Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. 7. Centre for Infection and Immunity, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
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 1s (FEV1) area under the curve from 0-4h (AUC0-4h) (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 AUC0-4h (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.
RCT Entities:
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 1s (FEV1) area under the curve from 0-4h (AUC0-4h) (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 AUC0-4h (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.
Authors: Rodrigo Abensur Athanazio; Luiz Vicente Ribeiro Ferreira da Silva Filho; Alberto Andrade Vergara; Antônio Fernando Ribeiro; Carlos Antônio Riedi; Elenara da Fonseca Andrade Procianoy; Fabíola Villac Adde; Francisco José Caldeira Reis; José Dirceu Ribeiro; Lídia Alice Torres; Marcelo Bicalho de Fuccio; Matias Epifanio; Mônica de Cássia Firmida; Neiva Damaceno; Norberto Ludwig-Neto; Paulo José Cauduro Maróstica; Samia Zahi Rached; Suzana Fonseca de Oliveira Melo Journal: J Bras Pneumol Date: 2017 May-Jun Impact factor: 2.624