期刊
RESPIRATORY MEDICINE
卷 106, 期 4, 页码 531-539出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.rmed.2011.10.020
关键词
AZD9668; Budesonide; COPD; Formoterol; Neutrophil elastase
资金
- Adamed
- ALK-Abello
- Allergopharma
- AstraZeneca
- Boehringer Ingelheim
- Chiesi
- GlaxoSmithKline
- Krka
- Meda
- Merck Sharp and Dohme
- Novartis
- Nycomed
- Stallergen
- UCB
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 Ilb, 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 0.01 L (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. (C) 2011 Elsevier Ltd. All rights reserved.
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