INTRODUCTION: The aim of this study was to establish the feasibility of using 
computed tomography (CT) in a multicenter setting to assess structural airway 
changes.
METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, Phase 
IIb trial using CT to investigate the effect of a novel, oral, reversible 
neutrophil elastase inhibitor, AZD9668 60 mg twice daily (BID), on structural 
airway changes in patients aged 50-80 years with chronic obstructive pulmonary 
disease (COPD) (ex-smokers).
PRIMARY OUTCOME VARIABLE: airway wall thickness at an extrapolated interior 
perimeter of 10 mm (AWT-Pi10). Secondary outcome variables: fifth-generation 
wall area %; air trapping index; pre- and post-bronchodilator forced expiratory 
volume in 1 s (FEV1); morning and evening peak expiratory flow and FEV1; body 
plethysmography; EXAcerbations of Chronic pulmonary disease Tool (EXACT); 
Breathlessness, Cough, and Sputum Scale (BCSS); St George's Respiratory 
Questionnaire for COPD; and proportion of reliever-medication-free trial days. 
Safety variables were also assessed.
RESULTS: There was no difference between placebo (n = 19) and AZD9668 (n = 17) 
for AWT-Pi10 at treatment end. This was consistent with results for most 
secondary variables. However, patients randomized to AZD9668 experienced an 
improvement versus placebo for morning and evening FEV1, and EXACT and BCSS 
cough and sputum scores. AZD9668 60 mg BID was well tolerated and no new safety 
concerns were identified.
CONCLUSIONS: This study confirmed the feasibility of using CT to assess 
structural airway changes in COPD. However, there was no evidence of 
improvements in CT structural measures following 12 weeks' treatment with 
AZD9668 60 mg BID.
FUNDING: AstraZeneca.