scholarly journals A scintigraphy study of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in patients with moderate-to-very severe chronic obstructive pulmonary disease

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Omar Usmani ◽  
Nicolas Roche ◽  
Ezanul Wahab ◽  
Samuel Israel ◽  
Martin Jenkins ◽  
...  
Keyword(s):  
Dose Inhaler ◽  
Chronic Obstructive ◽  
Metered Dose Inhaler ◽  
Obstructive Pulmonary Disease ◽  
Deposition Patterns ◽  
Metered Dose ◽  
The Mean ◽  
Long Acting ◽  
Severe Copd ◽  
Formoterol Fumarate

Abstract Background 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%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD. Methods This 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. Results The 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). Conclusions Radiolabeled 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

scholarly journals Functional respiratory imaging assessment of glycopyrrolate and formoterol fumarate metered dose inhalers formulated using co-suspension delivery technology in patients with COPD

2020 ◽  
Vol 14 ◽  
pp. 175346662091699
Author(s):  
Wilfried De Backer ◽  
Jan De Backer ◽  
Ilse Verlinden ◽  
Glenn Leemans ◽  
Cedric Van Holsbeke ◽  
...  
Keyword(s):  
Dose Inhaler ◽  
Chronic Obstructive ◽  
Body Plethysmography ◽  
Metered Dose Inhaler ◽  
Double Blind ◽  
Obstructive Pulmonary Disease ◽  
Number Of Patients ◽  
Metered Dose ◽  
Long Acting ◽  
Formoterol Fumarate

Background: Functional respiratory imaging (FRI) is a quantitative postprocessing imaging technique used to assess changes in the respiratory system. Using FRI, we characterized the effects of the long-acting muscarinic antagonist (LAMA), glycopyrrolate metered dose inhaler (GP MDI), and the long-acting β2-agonist (LABA), formoterol fumarate metered dose inhaler (FF MDI), on airway volume and resistance in patients with moderate-to-severe chronic obstructive pulmonary disease. Methods: Patients in this phase IIIb, randomized, double-blind crossover study received twice-daily GP MDI (18 μg) and FF MDI (9.6 μg). Primary endpoints were specific (i.e. corrected for lobar volume) image-based airway volume (siVaw) and specific image-based airway resistance (siRaw), measured using FRI. Secondary and other endpoints included additional FRI, spirometry, and body plethysmography parameters. Postdose efficacy assessments were performed within 60–150 min of dosing on day 15. Results: A total of 23 patients were randomized and 19 completed both treatment periods. GP MDI and FF MDI both achieved significant improvements from baseline to day 15 in siVaw [11% ( p = 0.0187) and 23% ( p < 0.0001) increases, respectively] and siRaw [25% ( p = 0.0219) and 44% ( p < 0.0001) reductions, respectively]. Although, on average, improvements were larger for FF MDI than GP MDI, some individuals displayed greater responses with each of the two treatments. These within-patient differences increased with airway generation number. Spirometry and body plethysmography endpoints showed significant improvements from baseline in inspiratory capacity for both treatments, and numeric improvements for other endpoints. Conclusion: Both GP MDI and FF MDI significantly improved siRaw and siVaw at day 15 versus baseline. FRI endpoints demonstrated increased sensitivity relative to spirometry and body plethysmography in detecting differences between treatments in a small number of patients. Intra-patient differences in treatment response between the LAMA and the LABA provide further support for the benefit of dual bronchodilator therapies. ClinicalTrials.gov registration number: NCT02937584 The reviews of this paper are available via the supplemental material section.

Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive Pulmonary Disease

2021 ◽  
pp. 106002802110383
Author(s):  
Stefanie C. Nigro ◽  
Diana M. Sobieraj
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Clinical Practice ◽  
Triple Therapy ◽  
Pulmonary Disease ◽  
Dose Inhaler ◽  
Chronic Obstructive ◽  
Metered Dose Inhaler ◽  
Obstructive Pulmonary Disease ◽  
Metered Dose ◽  
Formoterol Fumarate

Objective: To review current evidence on the use of a fixed-dose combination (FDC) of budesonide/glycopyrrolate/formoterol fumarate (BGFF) triple therapy delivered via metered dose inhaler (MDI) in patients with chronic obstructive pulmonary disease (COPD) and offer clinical practice insights. Data Sources: We used PubMed to conduct the literature search from 1946 through June 30, 2021, using budesonide, glycopyrrolate or glycopyrronium, and formoterol. Study Selection and Extraction: We included clinical trials in patients with COPD along with pharmacokinetic or pharmacodynamic studies. Data Synthesis: In all, 19 citations were included. BGFF MDI reduces the risk of exacerbations regardless of exacerbation history compared with dual bronchodilators or inhaled corticosteroid/long-acting β-agonist. Rescue inhaler use decreased, and patient-reported outcomes of symptoms and well-being improved with triple therapy. Mortality was decreased with the higher-dose BGFF MDI in comparison to dual bronchodilator therapy. Dysphonia and candidiasis were more common with BGFF MDI compared with dual bronchodilators, as was pneumonia. Relevance to Patient Care and Clinical Practice: BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia. Conclusion: The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.

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