title: Fast onset of action of glycopyrronium compared with tiotropium in patients with moderate to severe COPD - A randomised, multicentre, crossover trial.
abstract: Long-acting bronchodilators, including anticholinergics glycopyrronium and tiotropium, are central to symptomatic management of chronic obstructive pulmonary disease (COPD). In patients with moderate to severe COPD, glycopyrronium has demonstrated comparable efficacy to open-label and single-blinded tiotropium, but with faster onset of bronchodilation. The FAST study assessed the efficacy of glycopyrronium compared with tiotropium in serial spirometry and body plethysmography assessments to further characterize the earlier onset of action associated with glycopyrronium.
  
  
  
  In this German multicentre, randomised, double-blinded, double-dummy, cross-over study, patients with moderate-to-severe COPD received single-dose of glycopyrronium 44 μg and tiotropium 18 μg via the Breezhaler®and Handihaler®devices, respectively. Primary objective was to demonstrate superiority of glycopyrronium over tiotropium in terms of improvement in forced expiratory volume in 1 s as assessed by the area under the curve from 0 to 2 h (FEV1AUC0-2h). Secondary endpoints were functional residual capacity (FRC), residual volume (RV), inspiratory capacity (IC), and specific airway resistance (sRaw), all measured by body plethysmography.
  
  
  
  Of the 152 patients randomised, 99.3% completed the study. After inhalation of the single dose, glycopyrronium demonstrated superiority over tiotropium in early bronchodilation as assessed by improvement in FEV1AUC0-2h(least squares mean treatment difference = 37 mL; 95% CI: 16, 59 mL; p < 0.01) and FEV1at 15 min post-dose (least square mean treatment difference = 36 mL; 95% CI: 14, 58 mL; p < 0.01). Both treatments showed similar improvements in FRCpleth, RV, and IC. Glycopyrronium showed statistically significant improvement in sRawcompared with tiotropium over the first 90 min after dosing, with the difference of 0.184 kPa × s at 90 min post-dose (95% CI: 0.315,0.054 kPa × s; p < 0.01).
  
  
  
  Glycopyrronium was superior to tiotropium in terms of early bronchodilation. Although both glycopyrronium and tiotropium showed similar improvements in static lung volume parameters, glycopyrronium reduced specific airway resistance faster than tiotropium, which could in part explain the earlier FEV1response seen with glycopyrronium.
  
  
  
  ClinicalTrials.govNCT01922271.
authors.affiliation: Pulmonary Research Institute at Lung Clinic Grosshansdorf GmbH, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: h.watz@pulmoresearch.de.
authors.forename: Henrik
authors.initials: H
authors.lastname: Watz
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany. Electronic address: claudia.mailaender@novartis.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mailänder
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany. Electronic address: christoph.may@novartis.com.
authors.forename: Christoph
authors.initials: C
authors.lastname: May
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany. Electronic address: monika.baier@novartis.com.
authors.forename: Monika
authors.initials: M
authors.lastname: Baier
authors.affiliation: Pulmonary Research Institute at Lung Clinic Grosshansdorf GmbH, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: a.kirsten@pulmoresearch.de.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Kirsten
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D005858:Germany; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007320:Inspiratory Capacity; D008297:Male; D008875:Middle Aged; D010993:Plethysmography, Whole Body; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012115:Residual Volume; D012720:Severity of Illness Index; D013147:Spirometry; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001993:Bronchodilator Agents; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: Airway resistance; Body plethysmography; Chronic obstructive pulmonary disease; Fast onset; Glycopyrronium; Tiotropium