AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase, 
a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy, 
safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with 
placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb 
trial (NCT00949975: approved by an Investigational Review Board), in patients 
with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was 
pre-bronchodilator forced expiratory volume in 1 second (FEV₁). Secondary 
endpoints included forced vital capacity and inspiratory capacity, peak 
expiratory flow, Breathlessness, Cough and Sputum Scale score, exercise 
capacity, quality of life (QoL), exacerbation assessments, safety and 
pharmacokinetics. Exploratory endpoints included inflammatory and tissue 
degradation biomarkers. A total of 838 patients were randomised to AZD9668 5 mg 
bid (212 patients), 20 mg bid (206 patients), 60 mg bid (202 patients) or 
placebo (218 patients). AZD9668 showed no effect on lung function, respiratory 
signs and symptoms, QoL or biomarkers. At end of treatment, the change in mean 
pre-bronchodilator FEV₁ for AZD9668 60 mg bid compared with placebo was 0.00L 
(95% confidence interval: -0.05, 0.04; p = 0.873). Overall, AZD9668 was well 
tolerated; the numbers of patients with adverse events (AEs), serious AEs and 
AEs leading to discontinuation were similar in each of the four study groups. 
AZD9668 60 mg bid showed no clinical benefit and no effect on biomarkers of 
inflammation or tissue degradation when added to tiotropium in patients with 
COPD. These results raise important questions for future investigation of 
anti-inflammatory and disease-modifying agents in patients with COPD.