title: Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: a randomized, placebo-controlled, double-blind, crossover study.
abstract: BACKGROUND
  Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD.
  
  
  OBJECTIVE
  This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD.
  
  
  METHODS
  In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV₁) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV₁ at 5 minutes post-dose.
  
  
  RESULTS
  109 patients were randomized, and 108 completed the study. The increase in FEV₁ 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV₁ 5 minutes post-dose were 23.1%, 9.2% and 6.4% for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated.
  
  
  CONCLUSIONS
  In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV₁ at 5 minutes post-dose.
  
  
  BACKGROUND
  Clinicaltrials.gov identifier: NCT01048333; AstraZeneca study code: D5127C00001.
authors.affiliation: Unit of Respiratory Clinical Pharmacology, Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy. Mario.cazzola@uniroma2.it
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
authors.forename: Paolo
authors.initials: P
authors.lastname: Palange
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Pilar
authors.initials: P
authors.lastname: Ausin
authors.forename: Lars-Goran
authors.initials: LG
authors.lastname: Carlsson
authors.forename: Jan
authors.initials: J
authors.lastname: Ekelund
authors.forename: Jan
authors.initials: J
authors.lastname: Lotvall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D000068299:Salmeterol Xinafoate
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D000068299:Salmeterol Xinafoate; D000420:Albuterol; D000068759:Formoterol Fumarate