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.