Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1673586
- author
- Kerstjens, Huib A. ; Bjermer, Leif LU ; Eriksson, Leif ; Dahlstrom, Kerstin and Vestbo, Jorgen
- organization
- publishing date
- 2010
- 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
- pmid:20466530
- 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
- 2016-04-01 14:50:24
- date last changed
- 2022-01-28 02:47:52
@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}},
keywords = {{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}},
doi = {{10.1016/j.rmed.2010.04.010}},
volume = {{104}},
year = {{2010}},
}