Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes

Adv Ther. 2015 Jun;32(6):548-66. doi: 10.1007/s12325-015-0215-3. Epub 2015 Jun 5.


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.

Trial registration: ClinicalTrials.gov NCT01054170.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Airway Remodeling*
  • Bronchodilator Agents / pharmacology*
  • Bronchodilator Agents / therapeutic use*
  • Double-Blind Method
  • Feasibility Studies
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pyridones / pharmacology*
  • Pyridones / therapeutic use*
  • Research Embryo Creation / methods*
  • Sulfones / pharmacology*
  • Sulfones / therapeutic use*
  • Tomography, X-Ray Computed


  • Bronchodilator Agents
  • Pyridones
  • Sulfones
  • N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamide

Associated data

  • ClinicalTrials.gov/NCT01054170