Abstract
BackgroundTriple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2-agonists (ICS/LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD.MethodsThis phase I, single-dose, open-label gamma scintigraphy imaging study (NCT03906045) was conducted in patients with moderate-to-very severe COPD. Patients received two actuations of BGF MDI (160/9/4.8 μg per actuation) radiolabeled with technetium‑99‑pertechnetate, not exceeding 5 MBq per actuation. Immediately following each inhalation, patients performed a breath-hold of up to 10 s, then exhaled into an exhalation filter. Gamma scintigraphy imaging of the anterior and posterior views of the lungs and stomach, and a lateral head and neck view, were performed immediately after exhalation. The primary objective of the study was to assess the pulmonary deposition of BGF. Secondary objectives assessed the deposited dose of radiolabeled BGF in the oropharyngeal and stomach regions, on the actuator, and on the exhalation filter in addition to regional airway deposition patterns in the lungs.ResultsThe mean BGF emitted dose deposited in the lungs was 32.1% (standard deviation [SD] 15.6) in patients with moderate-to-very severe COPD, 35.2% (SD 12.8) in patients with moderate COPD, and 28.7% (SD 18.4) in patients with severe/very severe COPD. Overall, the mean normalized outer/inner ratio was 0.55 (SD 0.19), while the standardized central/peripheral ratio was 2.21 (SD 1.64).ConclusionsRadiolabeled BGF 320/18/9.6 μg was efficiently delivered and deposited throughout the entire lung, including large and small airways, in patients with moderate-to-very severe COPD, with similar deposition in patients with moderate COPD and patients with severe/very severe COPD.Trial registration: ClinicalTrials.gov, NCT03906045. Registered 8 April 2019, https://clinicaltrials.gov/ct2/show/NCT03906045
Highlights
Patients with chronic obstructive pulmonary disease (COPD) may be prescribed treatment with triple therapy if they continue to experience symptoms or exacerbations with dual therapies (LAMA/LABA or ICS/LABA) [1].Ideally, an inhaled treatment would be consistently deposited in all parts of the lung, including the peripheral airways [2]
Radiolabeling validation The Next Generation Impactor (NGI) analytical tests conducted during radiolabeling method development demonstrated that the aerodynamic size distribution of the emitted aerosol particles for each of the analytes, i.e. budesonide, glycopyrronium, and formoterol fumarate, were comparable to those from the non-radiolabeled canisters, confirming that the radiolabeling process did not alter the performance relative to that of the control nonradiolabeled metered dose inhaler (MDI)
The fine particle fraction for radiolabeled budesonide ranged from 48.69–56.48%, for glycopyrronium ranged from 51.43–59.45%, and for formoterol fumarate ranged from 49.31–56.76%
Summary
Patients with chronic obstructive pulmonary disease (COPD) may be prescribed treatment with triple therapy (inhaled corticosteroid/long-acting muscarinic antagonist/ long-acting β2-agonist [ICS/LAMA/LABA]) if they continue to experience symptoms or exacerbations with dual therapies (LAMA/LABA or ICS/LABA) [1]. An inhaled treatment would be consistently deposited in all parts of the lung, including the peripheral airways [2]. Triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2-agonists (ICS/ LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). We report the findings assessing BGF in patients with moderate-to-very severe COPD
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