A randomized study using FRI to characterize bronchodilator effects of glycopyrrolate formoterol fumarate delivered by a metered dose inhaler using co-suspension delivery technology in patients with COPD
International Journal of Chronic Obstructive Pulmonary Disease
Published 30 August 2018 Volume 2018:13 Pages 2673—2684
Wilfried De Backer, Jan De Backer, Wim Vos, Ilse Verlinden, Cedric Van holsbeke, Johan Clukers, Bita hajian, shahid siddiqui, Martin Jenkins, Colin reisner, Ubaldo J Martin
Functional respiratory imaging (FRI) uses high-resolution computed tomography (HRCT) scans to assess changes in airway volume and resistance.
Patients and methods:
In this randomized, double-blind, 2-week, crossover, Phase IIIB study, patients with moderate-to-severe COPD received twice-daily glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler (GFF MDI, 18/9.6 μg) and placebo MDI, for-mulated using innovative co-suspension delivery technology. Co-primary endpoints included the following: specific image-based airway volume (siVaw) and specific image-based airway resistance (siRaw) at Day 15, measured using FRI. Secondary and other endpoints included the following: change from baseline in post-dose forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC; spirometry) and ratio to baseline in post-dose functional residual capacity (FRC) and residual volume (RV; body plethysmography).Results: Twenty patients (46–78 years of age) were randomized and treated; of whom 19 completed the study. GFF MDI treatment increased siVaw by 75% and reduced siRaw by 71% vs placebo MDI (both P,0.0001). Image-based airway volume (iVaw) and image-based airway resistance (iRaw), without adjusting for lobe volume, demonstrated corresponding findings to the co-primary endpoint, as lobe volumes did not change with either treatment. Approximately 48% of the delivered dose of glycopyrronium and formoterol fumarate was estimated to be deposited in the lungs. Compared with placebo, GFF MDI treatment improved post-dose FEV1and IC (443 mL and 454 mL, respectively; both P,0.001) and reduced FRC and RV (13% and 22%, respectively; both P,0.0001). There were no significant safety findings.
Conclusion: GFF MDI demonstrated significant, clinically meaningful benefits on FRI-based airway volume and resistance in patients with moderate-to-severe COPD. Benefits were associated with improvements in FEV1, IC, and hyperinflation.
Clinical trial registration:
Keywords: GFF MDI, airway volume, airway resistance, inspiratory capacity, hyperinflation, LAMA/LABA
© 2018 De Backer et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non-Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). International Journal of COPD 2018:13 2673–268
Categorised in: Papers / September 1, 2018 5:38 pm /Tags: COPD, FRI