AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD.
Respir Med
; 106(4): 531-9, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22197578
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Sulfonas
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Broncodilatadores
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Budesonida
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Doença Pulmonar Obstrutiva Crônica
/
Etanolaminas
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Respir Med
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Polônia