title: 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 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).
  
  
  CONCLUSIONS
  Tiotropium was well tolerated in patients with CF; lung function improvements compared with placebo were not statistically significant in the phase 3 trial.
  
  
  RESULTS
  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.affiliation: 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.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, CT, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Koker
authors.affiliation: Florida State University College of Medicine, Orlando, FL, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Geller
authors.affiliation: Boehringer Ingelheim France SAS, Reims, France.
authors.forename: Berengere
authors.initials: B
authors.lastname: Langellier-Cocteaux
authors.affiliation: Boehringer Ingelheim France SAS, Reims, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Le Maulf
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kattenbeck
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Moroni-Zentgraf
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast, Northern Ireland, United Kingdom.
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005540:Forced Expiratory Flow Rates / Q000502:physiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D000069447:Tiotropium Bromide / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018680:Cholinergic Antagonists; D000069447:Tiotropium Bromide
keywords: Bronchodilator; Cystic fibrosis; Respimat; Tiotropium