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Int J Chron Obstruct Pulmon Dis. 2018 Aug 30;13:2673-2684. doi: 10.2147/COPD.S171707. eCollection 2018.

A randomized study using functional respiratory imaging to characterize bronchodilator effects of glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler using co-suspension delivery technology in patients with COPD.

Author information

1
Department of Respiratory Medicine, University of Antwerp, Antwerp, Belgium, wilfried.debacker@uantwerpen.be.
2
FLUIDDA, Los Angeles, CA, USA.
3
FLUIDDA, Kontich, Belgium.
4
AstraZeneca, Gaithersburg, MD, USA.
5
AstraZeneca, Cambridge, UK.
6
Pearl - A member of the AstraZeneca Group, Morristown, NJ, USA.

Abstract

Background:

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, formulated 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 FEV1 and 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:

ClinicalTrials.gov: NCT02643082.

KEYWORDS:

GFF MDI; LAMA/LABA; airway resistance; airway volume; hyperinflation; inspiratory capacity

PMID:
30214185
PMCID:
PMC6124470
DOI:
10.2147/COPD.S171707
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosure WDB, JC, and BH have no real or perceived conflicts of interest that relate to this manuscript. WDB’s department has received grants from AstraZeneca, Chiesi, and GlaxoSmithKline. JDB is the Chief Executive Officer and founder of FLUIDDA and holds shares in the company. WV is an employee of FLUIDDA and holds shares in the company. IV and CVH are employees of FLUIDDA. SS, MJ, and UJM are employees of AstraZeneca. CR is the Chief Executive Officer of Pearl – a member of the AstraZeneca Group – and an employee of AstraZeneca. All Pearl and AstraZeneca employees own AstraZeneca stocks. The authors report no other conflicts of interest in this work.

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