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Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD.

Bjermer, Leif LU ; Bengtsson, Thomas; Jorup, Carin and Lötvall, Jan (2012) In Respiratory Medicine
Abstract
There is still a need for new agents which improve upon the therapeutic index of tiotropium, the current standard of care for many patients with chronic obstructive pulmonary disease (COPD). We examined in patients with COPD the efficacy of single doses of AZD9164, an M(3)-selective muscarinic antagonist, to identify an appropriate dose-range for future studies. COPD patients (n = 28) inhaled AZD9164 (100, 400 and 1200 μg), tiotropium (18 μg) and placebo at 5 study centre visits (Clinicaltrials.gov identifier NCT00939211). The effects of these test drugs on average (E(av)), peak (E(max)) and trough (E(22-26)) forced expiratory volume in one second (FEV(1)) were assessed, as were systemically-mediated effects and the safety and exposure of... (More)
There is still a need for new agents which improve upon the therapeutic index of tiotropium, the current standard of care for many patients with chronic obstructive pulmonary disease (COPD). We examined in patients with COPD the efficacy of single doses of AZD9164, an M(3)-selective muscarinic antagonist, to identify an appropriate dose-range for future studies. COPD patients (n = 28) inhaled AZD9164 (100, 400 and 1200 μg), tiotropium (18 μg) and placebo at 5 study centre visits (Clinicaltrials.gov identifier NCT00939211). The effects of these test drugs on average (E(av)), peak (E(max)) and trough (E(22-26)) forced expiratory volume in one second (FEV(1)) were assessed, as were systemically-mediated effects and the safety and exposure of single doses of AZD9164. AZD9164 100, 400 and 1200 μg caused increases in FEV(1) to peak effects of 12, 17 and 12% above baseline respectively, following an initial transient and dose-related fall in FEV(1) and associated increase in mild respiratory symptoms such as cough. Bronchodilation was maintained overnight, with minimal FEV(1) decline. AZD9164 400 and 1200 μg produced larger effects than tiotropium on E(22-26) (p < 0.05; both doses) while AZD9164 400 μg also had larger effects on E(max) (p = 0.001) and E(av) (p < 0.05). There were no serious adverse events and statistically significant systemic effects were observed only with AZD9164 1200 μg. AZD9164 may improve upon the therapeutic index of tiotropium, increasing the magnitude and duration of lung function improvements without increasing systemically-mediated adverse events. The initial bronchoconstrictor effect of AZD9164 requires further investigation. (Less)
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author
organization
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type
Contribution to journal
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published
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Respiratory Medicine
publisher
Elsevier
external identifiers
  • WOS:000314135600010
  • PMID:23098686
  • Scopus:84871371932
ISSN
1532-3064
DOI
10.1016/j.rmed.2012.09.014
language
English
LU publication?
yes
id
d2e03e6e-6e1e-46ec-bed2-45089c8e4107 (old id 3160314)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23098686?dopt=Abstract
date added to LUP
2012-11-01 11:45:13
date last changed
2016-10-13 04:36:05
@misc{d2e03e6e-6e1e-46ec-bed2-45089c8e4107,
  abstract     = {There is still a need for new agents which improve upon the therapeutic index of tiotropium, the current standard of care for many patients with chronic obstructive pulmonary disease (COPD). We examined in patients with COPD the efficacy of single doses of AZD9164, an M(3)-selective muscarinic antagonist, to identify an appropriate dose-range for future studies. COPD patients (n = 28) inhaled AZD9164 (100, 400 and 1200 μg), tiotropium (18 μg) and placebo at 5 study centre visits (Clinicaltrials.gov identifier NCT00939211). The effects of these test drugs on average (E(av)), peak (E(max)) and trough (E(22-26)) forced expiratory volume in one second (FEV(1)) were assessed, as were systemically-mediated effects and the safety and exposure of single doses of AZD9164. AZD9164 100, 400 and 1200 μg caused increases in FEV(1) to peak effects of 12, 17 and 12% above baseline respectively, following an initial transient and dose-related fall in FEV(1) and associated increase in mild respiratory symptoms such as cough. Bronchodilation was maintained overnight, with minimal FEV(1) decline. AZD9164 400 and 1200 μg produced larger effects than tiotropium on E(22-26) (p &lt; 0.05; both doses) while AZD9164 400 μg also had larger effects on E(max) (p = 0.001) and E(av) (p &lt; 0.05). There were no serious adverse events and statistically significant systemic effects were observed only with AZD9164 1200 μg. AZD9164 may improve upon the therapeutic index of tiotropium, increasing the magnitude and duration of lung function improvements without increasing systemically-mediated adverse events. The initial bronchoconstrictor effect of AZD9164 requires further investigation.},
  author       = {Bjermer, Leif and Bengtsson, Thomas and Jorup, Carin and Lötvall, Jan},
  issn         = {1532-3064},
  language     = {eng},
  publisher    = {ARRAY(0xbaade00)},
  series       = {Respiratory Medicine},
  title        = {Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD.},
  url          = {http://dx.doi.org/10.1016/j.rmed.2012.09.014},
  year         = {2012},
}