Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults

Dorinsky, Paul; DePetrillo, Paolo B.; DeAngelis, Kiernan; Trivedi, Roopa; Darken, Patrick; Gillen, Michael

doi:10.1016/j.clinthera.2020.02.012

Cited by 7 publications

(10 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that despite training, some patients had a suboptimal MDI inhalation technique. If this is the case, delivery of BGF can be improved with a spacer device [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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

Usmani

Roche

Wahab³

et al. 2021

Respir Res

Self Cite

View full text Add to dashboard Cite

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

show abstract

“…It is possible that despite training, some patients had a suboptimal MDI inhalation technique. If this is the case, delivery of BGF can be improved with a spacer device [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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

Usmani

Roche

Wahab³

et al. 2021

Respir Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…Healthy individuals inhaling a single dose of BGFF through a VHC (eg, spacer) had higher total systemic exposure to budesonide and glycopyrronium along with greater lung exposure for all 3 drug components, without increasing adverse events. 10 This increase was mitigated when activated charcoal was given concomitantly with BGFF, suggesting that gastrointestinal absorption appreciably affects systemic bioavailability. 10 Adding a VHC led to an increase in systemic exposure and lung bioavailability (measured as AUC 0-t and C max ) in those with purported poor inhaler technique.…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…10 This increase was mitigated when activated charcoal was given concomitantly with BGFF, suggesting that gastrointestinal absorption appreciably affects systemic bioavailability. 10 Adding a VHC led to an increase in systemic exposure and lung bioavailability (measured as AUC 0-t and C max ) in those with purported poor inhaler technique. 10 The level of drug exposure observed in these individuals was comparable to the level in those considered to have good inhalation technique, not requiring a spacer.…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…42 Unlike DPIs, MDIs can be used with a spacer for patients struggling with inhaler technique, which could improve drug delivery in those with suboptimal inhalation technique. 10 Because medication nonadherence has far-reaching consequences, ensuring patients are prescribed the right type of inhaler is of utmost importance.…”

Section: Relevance To Patient Care and Clinical Practicementioning

confidence: 99%

“…10 Adding a VHC led to an increase in systemic exposure and lung bioavailability (measured as AUC 0-t and C max ) in those with purported poor inhaler technique. 10 The level of drug exposure observed in these individuals was comparable to the level in those considered to have good inhalation technique, not requiring a spacer.…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 99%

See 2 more Smart Citations

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

Nigro

Sobieraj

2021

Ann Pharmacother

View full text Add to dashboard Cite

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.

show abstract

Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential

Aurivillius,

Bednarczyk,

Kokot

et al. 2023

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults

Cited by 7 publications

References 13 publications

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

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

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

Relative bioavailability of budesonide/glycopyrrolate/formoterol fumarate triple therapy delivered using next generation propellants with low global warming potential

Contact Info

Product

Resources

About