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Respir Med. 2012 Apr;106(4):531-9. doi: 10.1016/j.rmed.2011.10.020. Epub 2011 Dec 23.

AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD.

Author information

1
Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland. piotr.kuna@umed.lodz.pl

Abstract

BACKGROUND:

Neutrophil elastase (NE) is implicated in chronic obstructive pulmonary disease (COPD). AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.

METHODS:

This 12-week, randomised, double-blind, placebo-controlled, Phase IIb, trial (NCT01023516), investigated the efficacy and safety of AZD9668 (60 mg bid) versus placebo in patients with symptomatic COPD and a history of exacerbation receiving maintenance budesonide/formoterol. Primary outcome variable: forced expiratory volume in one second (FEV1). Secondary endpoints included: post-bronchodilator FEV1, pre- and post-bronchodilator forced vital capacity, FEV6, forced expiratory flow between 25% and 75% of vital capacity and inspiratory capacity; peak expiratory flow and FEV1 measured at home; EXAcerbations of Chronic pulmonary disease Tool and Breathlessness, Cough and Sputum Scores; St George's respiratory questionnaire for COPD (SGRQ-C) scores; exacerbations; and safety assessments.

RESULTS:

Six hundred and fifteen patients were randomised: placebo (302), AZD9668 60 mg bid (313). AZD9668 showed no effect on lung function: change in mean pre-bronchodilator FEV1 versus placebo was 0.01L (95% confidence interval: -0.03, 0.05; p=0.533). AZD9668 did not significantly improve respiratory signs and symptoms, SGRQ-C score or time to first exacerbation. Adverse events were similar for AZD9668 and placebo.

CONCLUSIONS:

Three months' treatment with AZD9668 did not improve lung function, respiratory signs and symptoms or SGRQ-C score when added to budesonide/formoterol maintenance therapy in patients with COPD. In the absence of definitive biomarkers of short-term disease progression, further research is needed to determine the optimal duration of studies to evaluate NE inhibitors as disease-modifying agents.

PMID:
22197578
DOI:
10.1016/j.rmed.2011.10.020
[Indexed for MEDLINE]
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