How much can a combination inhaler open the airways of people with moderate-to-severe COPD?

Details

Functional respiratory imaging (FRI) uses high-resolution computed tomography (HRCT) scans to assess changes in airway volume and resistance.

This randomized, double-blind, 2-week, crossover, Phase IIIB study involved patients with moderate-to-severe COPD. Patients received twice-daily glycopyrrolate/formoterol fumarate through a metered dose inhaler (GFF MDI, 18/9.6 µg) and placebo MDI, formulated using innovative co-suspension delivery technology.

The co-primary endpoints were specific image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI on Day 15. Secondary and other endpoints included changes from baseline in post-dose forced expiratory volume in 1 second (FEV1) and inspiratory capacity (IC), measured by spirometry, and ratios to baseline in post-dose functional residual capacity (FRC) and residual volume (RV), measured by body plethysmography.

Twenty patients aged 46–78 years were randomized and treated; 19 completed the study. Compared with placebo MDI, GFF MDI increased siVaw by 75% and reduced siRaw by 71% (both P <0.0001). Image-based airway volume (iVaw) and image-based airway resistance (iRaw) without adjustment for lobe volume showed corresponding findings to the co-primary endpoints; lobe volumes did not change with either treatment.

An estimated approximately 48% of the delivered dose of glycopyrronium and formoterol fumarate was deposited in the lungs. Compared with placebo, GFF MDI improved post-dose FEV1 by 443 mL and IC by 454 mL (both P <0.001), and reduced FRC by 13% and RV by 22% (both P <0.0001). There were no significant safety findings.

The authors concluded that GFF MDI provided significant, clinically meaningful benefits in FRI-based airway volume and resistance in patients with moderate-to-severe COPD. These benefits were associated with improvements in FEV1, IC, and hyperinflation.

Clinical trial registration: ClinicalTrials.gov: NCT02643082. Keywords: GFF MDI, airway volume, airway resistance, inspiratory capacity, hyperinflation, LAMA/LABA.