title: Sustained 24-hour efficacy of once daily indacaterol (300 μg) in patients with chronic obstructive pulmonary disease: a randomized, crossover study.
abstract: OBJECTIVE
  Indacaterol is a novel, once daily, inhaled ultra-long-acting β₂-agonist for the treatment of chronic obstructive pulmonary disease (COPD). Here we compared the 24-h spirometry profile of once daily indacaterol 300 μg with that of placebo and twice daily salmeterol 50 μg in patients with COPD.
  
  
  METHODS
  This randomized, multicenter, placebo-controlled, crossover study comprised three 14-day treatment periods (with 14-day washouts). Patients (male/female ≥ 40 years) with moderate-to-severe COPD were randomized to receive double-blind indacaterol 300 μg or placebo once daily, or open-label salmeterol 50 μg twice daily. The primary outcome measure was 24-h post-dose (trough) FEV₁ (mean of FEV₁ at 23 h 10 min and 23 h 45 min post-indacaterol dose) after 14 days. FEV₁ was assessed at multiple time points on Days 1 and 14 of each treatment period. Safety and tolerability were also monitored.
  
  
  RESULTS
  Of 68 randomized patients, 61 completed. Trough FEV₁ (primary endpoint) on Day 14 for indacaterol was 200 mL higher than placebo (p < 0.001), exceeding the prespecified minimum clinically important difference (120 mL), and was 90 mL higher than for salmeterol (p = 0.011). After Day 1, trough FEV(1) for indacaterol was 150 mL higher than placebo (p < 0.001). Indacaterol provided superior bronchodilation compared with placebo (p < 0.001) across the full 24-h assessment period on Days 1 and 14. In addition, on both days, indacaterol provided superior FEV₁ compared with salmeterol (p < 0.05) at many post-baseline time points, including 5 min post-dose. All treatments were well tolerated.
  
  
  CONCLUSIONS
  Once daily indacaterol 300 μg produced effective sustained 24-h bronchodilation from the first dose, an efficacy profile superior to placebo and twice daily salmeterol. Given its effective bronchodilation with once daily dosing, indacaterol is likely to be a useful treatment option for patients with moderate-to-severe COPD.
authors.affiliation: North Carolina Clinical Research, Raleigh, NC, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Laforce
authors.forename: Joseph
authors.initials: J
authors.lastname: Aumann
authors.forename: Luis
authors.initials: L
authors.lastname: de Teresa Parreño
authors.forename: Amir
authors.initials: A
authors.lastname: Iqbal
authors.forename: David
authors.initials: D
authors.lastname: Young
authors.forename: Roger
authors.initials: R
authors.lastname: Owen
authors.forename: Mark
authors.initials: M
authors.lastname: Higgins
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kramer
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; C510790:indacaterol