Bronchodilatory effects of aclidinium bromide, a long-acting muscarinic antagonist, in COPD patients.
BACKGROUND
Aclidinium bromide is a novel, long-acting, inhaled muscarinic antagonist bronchodilator currently in Phase III clinical development for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending doses of aclidinium bromide in patients with COPD.


METHODS
This double-blind, randomised, placebo-controlled, crossover study was conducted in patients with moderate to severe COPD (forced expiratory volume in 1s [FEV(1)] <65% predicted). Patients were randomly assigned to one of four treatment sequences of aclidinium bromide 100, 300, 900microg and placebo with a washout period between doses. The primary outcome was area under the FEV(1) curve over the 0-24h time interval.


RESULTS
Seventeen patients with COPD were studied. Mean FEV(1) over 24h was 1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300 and 900microg, respectively (p<0.001 vs. placebo, all doses). Significant changes from baseline in FEV(1) were detected 15min post-dose for aclidinium bromide 300 and 900microg, with a peak effect 2h post-dose (all doses). Aclidinium bromide was undetected in plasma. The majority of adverse events was unrelated to study medication and did not result in discontinuation.


CONCLUSIONS
Aclidinium bromide 100-900microg produced sustained bronchodilation over 24h in patients with COPD.
Joos
G F
GF
Department of Respiratory Medicine, Ghent University Hospital, De Pintelaan 185, B9000 Ghent, Belgium. guy.joos@ugent.be
Schelfhout
V J
VJ
Pauwels
R A
RA
Kanniess
F
F
Magnussen
H
H
Lamarca
R
R
Jansat
J M
JM
Garcia Gil
E
E
D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004812:Epidemiologic Methods; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D014326:Tropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D018727:Muscarinic Antagonists; D014326:Tropanes; C542859:aclidinium bromide