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Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

Kerstjens, Huib A.; Bjermer, Leif LU ; Eriksson, Leif; Dahlstrom, Kerstin and Vestbo, Jorgen (2010) In Respiratory Medicine 104(9). p.1297-1303
Abstract
Objective: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. Methods: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300 mu g or placebo twice daily via Turbuhaler (R) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment. Results: Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n = 33) or placebo (n = 32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV1... (More)
Objective: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. Methods: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300 mu g or placebo twice daily via Turbuhaler (R) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment. Results: Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n = 33) or placebo (n = 32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV1 (AZD4818-placebo: 0.026 L, p = 0.69), morning PEF (-6 L/min, p = 0.23), or other lung function measures. There was no difference between treatment groups in the 6-min walk test, MMRC dyspnoea index, BODE index and CCQ scores. Plasma concentrations indicated that patients were exposed to AZD4818 as expected. AZD4818 was well tolerated: 27 treatment-related adverse events (13 with AZD4818, 14 with placebo), 2 serious adverse events (both AZD4818: exacerbation [considered not treatment-related] and deep vein thrombosis [considered treatment-related]) and 11 discontinuations (7 with AZD4818). Conclusions: Inhaled AZD4818 was well tolerated at 300 mu g twice daily for 4 weeks in patients with COPD; however, there was no indication of a beneficial treatment effect despite exposure as expected. These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas. (C) 2010 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chemokine receptor antagonist, COPD, AZD4818, Disease modification
in
Respiratory Medicine
volume
104
issue
9
pages
1297 - 1303
publisher
Elsevier
external identifiers
  • wos:000281084400008
  • scopus:77955664554
ISSN
1532-3064
DOI
10.1016/j.rmed.2010.04.010
language
English
LU publication?
yes
id
35ef3685-3ac1-4c8f-a172-c667d9fb905d (old id 1673586)
date added to LUP
2010-09-23 09:49:07
date last changed
2018-07-15 04:00:41
@article{35ef3685-3ac1-4c8f-a172-c667d9fb905d,
  abstract     = {Objective: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. Methods: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300 mu g or placebo twice daily via Turbuhaler (R) for 4 weeks. Safety, lung function, functional capacity and health status measures were measured. Plasma concentrations of AZD4818 were measured after the first dose and after 2 and 4 weeks' treatment. Results: Sixty-five patients (47 male; median age 65.6 years) received AZD4818 (n = 33) or placebo (n = 32). There was no statistically significant difference between AZD4818 and placebo in change from baseline to endpoint for FEV1 (AZD4818-placebo: 0.026 L, p = 0.69), morning PEF (-6 L/min, p = 0.23), or other lung function measures. There was no difference between treatment groups in the 6-min walk test, MMRC dyspnoea index, BODE index and CCQ scores. Plasma concentrations indicated that patients were exposed to AZD4818 as expected. AZD4818 was well tolerated: 27 treatment-related adverse events (13 with AZD4818, 14 with placebo), 2 serious adverse events (both AZD4818: exacerbation [considered not treatment-related] and deep vein thrombosis [considered treatment-related]) and 11 discontinuations (7 with AZD4818). Conclusions: Inhaled AZD4818 was well tolerated at 300 mu g twice daily for 4 weeks in patients with COPD; however, there was no indication of a beneficial treatment effect despite exposure as expected. These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas. (C) 2010 Elsevier Ltd. All rights reserved.},
  author       = {Kerstjens, Huib A. and Bjermer, Leif and Eriksson, Leif and Dahlstrom, Kerstin and Vestbo, Jorgen},
  issn         = {1532-3064},
  keyword      = {Chemokine receptor antagonist,COPD,AZD4818,Disease modification},
  language     = {eng},
  number       = {9},
  pages        = {1297--1303},
  publisher    = {Elsevier},
  series       = {Respiratory Medicine},
  title        = {Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients},
  url          = {http://dx.doi.org/10.1016/j.rmed.2010.04.010},
  volume       = {104},
  year         = {2010},
}