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

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Abstract

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.

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Acknowledgments

We thank the investigators and patients for their participation in this study, and the study team for their involvement. We acknowledge Asger Dirksen, the international co-ordinating investigator, Goutham Edula, the Study Team Physician responsible for the CT imaging protocol, and Chris O’Brien, AstraZeneca’s Responsible Medical Officer (both formerly of AstraZeneca) for their contributions to this study. The study and article processing charges were funded by AstraZeneca, Södertälje, Sweden, who designed the study and were involved in the collection, analysis, and interpretation of data, in the writing of the manuscript (through the authors, who are AstraZeneca employees), and in the decision to submit the manuscript for publication. Medical writing assistance was provided by Lauren Donaldson, PhD from Complete Medical Communications, funded by AstraZeneca. All authors had full access to all the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published.

Conflict of interest

Lars Nordenmark and Carin Jorup are employees and shareholders of AstraZeneca. Rosemary Taylor is a contractor for AstraZeneca.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

Author information

Authors and Affiliations

  1. AstraZeneca R&D, Mölndal, Sweden

    Lars H. Nordenmark & Carin Jorup

  2. AstraZeneca R&D, Macclesfield, UK

    Rosemary Taylor

Authors
  1. Lars H. Nordenmark
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  2. Rosemary Taylor
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  3. Carin Jorup
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Corresponding author

Correspondence to Lars H. Nordenmark.

Additional information

Clinical trial registration number: ClinicalTrials.gov #NCT01054170.

Electronic supplementary material

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Nordenmark, L.H., Taylor, R. & Jorup, C. Feasibility of Computed Tomography in a Multicenter COPD Trial: A Study of the Effect of AZD9668 on Structural Airway Changes. Adv Ther 32, 548–566 (2015). https://doi.org/10.1007/s12325-015-0215-3

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  • DOI: https://doi.org/10.1007/s12325-015-0215-3

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