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A randomised, placebo-controlled study of the CXCR2 antagonist AZD5069 in bronchiectasis

Lookup NU author(s): Professor Anthony De SoyzaORCiD

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Abstract

This randomised double-blind placebo-controlled parallel-group multicentre phase ha study evaluated the effect of the CXCR2 antagonist AZD5069 on sputum neutrophil counts in adults with bronchiectasis.Patients were randomised 1:1 to receive AZD5069 80 mg or placebo orally twice daily for 28 days. Assessments included blood cell counts, inflammatory markers in blood, morning spontaneous sputum, lung function, safety and tolerability and patients completed daily BronkoTest diary cards. The primary outcome measure was the change in absolute sputum neutrophil count.Of 52 randomised patients, 45 completed treatment, 20 (76.9%) out of 26 receiving AZD5069 and 25 (96.2%) out of 26 receiving placebo. AZD5069 reduced the absolute neutrophil cell count in morning sputum by 69% versus placebo (p=0.004); percentage sputum neutrophil count was reduced by 36% (p=0.008). The number of infections/exacerbations was similar with AZD5069 and placebo (nine versus eight), but these led to more study discontinuations with AZD5069 (four versus zero). Sputum interleukin (IL)-6 and growth-regulated oncogene (GRO)-alpha and serum GRO-alpha, IL-1ss and IL-8 levels increased with AZD5069 versus placebo (all p<0.001), while serum high-sensitivity C-reactive protein levels did not change. AZD5069 was well tolerated.AZD5069 markedly reduced absolute sputum neutrophil counts in bronchiectasis patients, although this was not associated with improvements in clinical outcomes in this exploratory study.


Publication metadata

Author(s): De Soyza A, Pavord I, Elborn JS, Smith D, Wray H, Puu M, Larsson B, Stockley R

Publication type: Article

Publication status: Published

Journal: European Respiratory Journal

Year: 2015

Volume: 46

Issue: 4

Pages: 1021-1032

Print publication date: 01/10/2015

Online publication date: 01/10/2015

Acceptance date: 28/05/2015

ISSN (print): 0903-1936

ISSN (electronic): 1399-3003

Publisher: European Respiratory Society

URL: http://dx.doi.org/10.1183/13993003.00148-2015

DOI: 10.1183/13993003.00148-2015


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