title: A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison.
abstract: This dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled beta2-agonist, in subjects clinically diagnosed with COPD. Comparative data with tiotropium were collected. In the double-blind, core period of the study, 635 subjects with COPD (prebronchodilator FEV(1)40% of predicted and > or =1.0L; FEV1/FVC <70%) were randomized to receive indacaterol 50, 100, 200 or 400microg or placebo via multi-dose dry powder inhaler, or indacaterol 400microg via single-dose dry powder inhaler, once daily for 7 days. After completing double-blind treatment and washout, a subset of subjects from each treatment group entered an open-label extension and received tiotropium 18microg once daily for 8 days. The primary efficacy variable was the trough bronchodilator effect: standardized area under the FEV1 curve between 22 and 24h post-dose (FEV1 AUC(22-24h)) on Day 1. Clinically relevant improvements versus placebo in FEV1 AUC(22-24h) were seen for 400 and 200microg doses on Day 1 and all doses on Day 7. All indacaterol doses significantly (P<0.05) increased FEV1 from 5min to 24h post-dose; the 400 and 200microg doses were most effective. All doses were well tolerated. Indacaterol trough FEV1 levels compared favorably with the improvement seen by Day 8 in subjects treated with tiotropium in the open-label extension. The results confirm that indacaterol has a 24-h duration of bronchodilator effect and a fast onset of action in COPD and suggest that indacaterol could be an effective once-daily inhaled beta2-agonist bronchodilator. Indacaterol demonstrated a good overall safety and tolerability profile.
authors.affiliation: University of Nebraska Medical Center, Pulmonary and Critical Care Medicine, Omaha, Nebraska 68198-5885, USA. srennard@unmc.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: Theo
authors.initials: T
authors.lastname: Bantje
authors.forename: Stefano
authors.initials: S
authors.lastname: Centanni
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.forename: Alexander
authors.initials: A
authors.lastname: Chuchalin
authors.forename: Anthony
authors.initials: A
authors.lastname: D'Urzo
authors.forename: Oliver
authors.initials: O
authors.lastname: Kornmann
authors.forename: Sheryl
authors.initials: S
authors.lastname: Perry
authors.forename: Damon
authors.initials: D
authors.lastname: Jack
authors.forename: Roger
authors.initials: R
authors.lastname: Owen
authors.forename: Mark
authors.initials: M
authors.lastname: Higgins
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012602:Scopolamine Derivatives / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C510790:indacaterol; D000069447:Tiotropium Bromide