Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis

J Stuart Elborn, John Perrett, Kristina Forsman-Semb, Joanna Marks-Konczalik, Kulasiri Gunawardena, Neil Entwistle

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The aim of this study was to evaluate the safety and effect on clinical outcomes and biomarkers of inflammation and tissue damage of the neutrophil elastase inhibitor AZD9668 (60 mg twice daily orally for 4 weeks) in cystic fibrosis. This was a randomised, double-blind, placebo-controlled study. Primary outcome measures were sputum neutrophil count, lung function, 24-h sputum weight, BronkoTest® diary card data and health-related quality-of-life (revised cystic fibrosis quality-of-life questionnaire). Secondary end-points included sputum neutrophil elastase activity, inflammatory biomarkers in sputum and blood, urine and plasma desmosine (an elastin degradation marker), AZD9668 levels and safety parameters (adverse events, routine haematology, biochemistry, electrocardiogram and sputum bacteriology). 56 patients were randomised, of which 27 received AZD9668. There was no effect for AZD9668 on sputum neutrophil counts, neutrophil elastase activity, lung function or clinical outcomes, including quality of life. In the AZD9668 group, there was a trend towards reduction in sputum inflammatory biomarkers with statistically significant changes in interleukin-6, RANTES and urinary desmosine. The pattern of adverse events was similar between groups. Consistent reductions in sputum inflammatory biomarkers were seen in the AZD9668 group, and reduction in urinary desmosine suggests that AZD9668 impacts elastin cleavage by neutrophil elastase.
Original languageEnglish
Pages (from-to)969-76
Number of pages8
JournalThe European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
Volume40
Issue number4
Early online date20 Jan 2012
DOIs
Publication statusPublished - 01 Oct 2012

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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