title: Activity of aclidinium bromide, a new long-acting muscarinic antagonist: a phase I study.
abstract: OBJECTIVE
  Aclidinium bromide is a muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). This phase I trial in healthy subjects investigated the bronchodilator activity of aclidinium and its ability to reduce methacholine-induced bronchoconstriction.
  
  
  METHODS
  This double-blind, partial-crossover study randomized 12 subjects to treatment with single doses of aclidinium (50, 300 or 600 microg) or placebo. Drug activity was assessed for 24 h after administration by specific airway conductance (sGaw), airways resistance (Raw) and bronchial responsiveness (PC35 sGaw methacholine).
  
  
  RESULTS
  Aclidinium significantly increased sGaw compared with placebo at all assessments and doses (sGaw mean +/- SD AUC (l kPa(-1) h) for placebo 24.4 +/- 4.37, for 50 microg 29.0 +/- 7.08, for 300 microg 31.2 +/- 6.68 and for 600 microg 32.7 +/- 7.95) (P < 0.009), except 50 microg at 1 and 24 h. Significant decreases in Raw were observed with aclidinium 300 and 600 microg compared with placebo at all assessments (Raw mean +/- SD AUC (kPa s(-1) l(-1) h) for placebo 7.7 +/- 3.46, for 300 microg 5.8 +/- 2.33, for 600 microg 6.3 +/- 3.11) (P < 0.04) except 600 microg at 24 h. Differences between aclidinium 300 and 600 microg vs. placebo in PC35 doubling concentration were significant at all assessments (mean +/- SD AUC (mg ml(-1) h) for placebo 100.0 +/- 30.27, for 50 microg 117.2 +/- 33.33, for 300 microg 168.9 +/- 28.66 and for 600 microg 179.1 +/- 15.73 (P < 0.0001). For all endpoints, there was a significant difference between aclidinium 50 microg and the higher doses (P < 0.0001). Aclidinium was not detected in plasma and was well tolerated.
  
  
  CONCLUSIONS
  Aclidinium produced statistically significant and sustained bronchodilation over 24 h, suggesting long-acting efficacy and providing a rationale for future studies in patients with COPD.
authors.affiliation: Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, B9000, Ghent, Belgium.
authors.forename: Vanessa J
authors.initials: VJ
authors.lastname: Schelfhout
authors.forename: Pau
authors.initials: P
authors.lastname: Ferrer
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Jansat
authors.forename: Francesc
authors.initials: F
authors.lastname: Peris
authors.forename: Esther Garcia
authors.initials: EG
authors.lastname: Gil
authors.forename: Romain A
authors.initials: RA
authors.lastname: Pauwels
authors.forename: Guy F
authors.initials: GF
authors.lastname: Joos
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D014326:Tropanes / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D014326:Tropanes; C542859:aclidinium bromide