AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in
patients with COPD.
Author(s): Kuna P, Jenkins M, O'Brien CD, Fahy WA.
Affiliation(s): Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital,
Medical University of Lodz, Lodz, Poland. piotr.kuna@umed.lodz.pl
Publication date & source: 2012, Respir Med. , 106(4):531-9
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.
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