Academic Journal
Exposure to Budesonide, Glycopyrronium, and Formoterol With a Next-Generation Propellant Does Not Exceed Exposure With Hydrofluoroalkane-134a Propellant When Administered Via Pressurized Metered-Dose Inhaler With a Spacer.
| Τίτλος: | Exposure to Budesonide, Glycopyrronium, and Formoterol With a Next-Generation Propellant Does Not Exceed Exposure With Hydrofluoroalkane-134a Propellant When Administered Via Pressurized Metered-Dose Inhaler With a Spacer. |
|---|---|
| Συγγραφείς: | Pandya H; Respiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Patel M; Respiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Gillen M; Creek Lane PK, LLC, Waterford, Virginia., Reddy J; Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, The Discovery Centre, Biomedical Campus, Cambridge, UK., Bednarczyk A; Respiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZeneca, AstraZeneca Pharma Poland, Warsaw, Poland., Kokot M; Respiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, AstraZeneca, AstraZeneca Pharma Poland, Warsaw, Poland., Tan Y; Respiratory and Immunology, Biometrics, BioPharmaceuticals R&D, AstraZeneca, Mississauga, Ontario, Canada., Heijer M; Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D AstraZeneca, Mölndal, Gothenburg, Sweden., Andersson M; Respiratory and Immunology, Clinical Operations, BioPharmaceuticals R&D, AstraZeneca, Mölndal, Gothenburg, Sweden., Petullo D; Respiratory and Immunology, Biometrics, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland., Jassal M; Respiratory and Immunology, Clinical Development, BioPharmaceuticals R&D, Gaithersburg, Maryland. Electronic address: mandeep.jassal@astrazeneca.com. |
| Πηγή: | Clinical therapeutics [Clin Ther] 2026 Jan; Vol. 48 (1), pp. 73-80. Date of Electronic Publication: 2025 Dec 04. |
| Τύπος έκδοσης: | Journal Article; Clinical Trial, Phase I; Randomized Controlled Trial |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Excerpta Medica Country of Publication: United States NLM ID: 7706726 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-114X (Electronic) Linking ISSN: 01492918 NLM ISO Abbreviation: Clin Ther Subsets: MEDLINE |
| Imprint Name(s): | Publication: 1998- : Belle Mead, NJ, : Excerpta Medica Original Publication: Princeton, N. J., Excerpta Medica. |
| Ιατρικοί όροι (MeSH): | Glycopyrrolate*/administration & dosage , Glycopyrrolate*/pharmacokinetics , Glycopyrrolate*/adverse effects , Hydrocarbons, Fluorinated*/administration & dosage , Hydrocarbons, Fluorinated*/pharmacokinetics , Hydrocarbons, Fluorinated*/adverse effects , Budesonide*/administration & dosage , Budesonide*/pharmacokinetics , Budesonide*/adverse effects , Aerosol Propellants*/administration & dosage , Aerosol Propellants*/pharmacokinetics , Aerosol Propellants*/adverse effects , Bronchodilator Agents*/administration & dosage , Bronchodilator Agents*/pharmacokinetics , Ethanolamines*/administration & dosage , Ethanolamines*/pharmacokinetics , Ethanolamines*/adverse effects , Metered Dose Inhalers*, Formoterol Fumarate/administration & dosage ; Humans ; Male ; Adult ; Middle Aged ; Female ; Drug Combinations ; Administration, Inhalation ; Young Adult ; Inhalation Spacers ; Cross-Over Studies ; Double-Blind Method ; Aged ; Fluorocarbons |
| Περίληψη: | Purpose: Hydrofluoroalkane-134a (HFA-134a), the propellant in the marketed budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) formulation, has a global warming potential (GWP) that falls above environmental regulation thresholds and therefore will be phased out. With global efforts to minimize carbon emissions, the hydrofluoroolefin-1234ze (HFO-1234ze) propellant, with a >99% lower GWP than HFA-134a, is in development for pressurized metered-dose inhalers (pMDIs). Spacers support drug delivery in patients with poor pMDI inhalation technique, but it is unknown if BGF exposure with HFO-1234ze exceeds that observed with HFA-134a when using a spacer. Methods: This Phase I study assessed systemic BGF component exposure with HFO-1234ze versus HFA-134a when using a spacer, and for HFO-1234ze with and without a spacer. Participants (N = 42) were randomized to BGF with HFA-134a with a spacer (reference), HFO-1234ze with a spacer (test), and HFO-1234ze without a spacer (descriptive treatment) over 3 treatment periods in 1 of 6 sequences. As spacer devices help to increase exposure, the upper limit of the 90% confidence interval (CI) of geometric mean ratios (GMRs) was of interest, and bioequivalence was not included as a study objective. Findings: Analyses demonstrated the upper 90% CI of the GMRs for maximum observed plasma concentration (Cmax) and area under the plasma concentration curve from time zero to the time of the last quantifiable concentration (AUClast) were <125% for all BGF components for HFO-1234ze versus HFA-134a when using a spacer, indicating exposure with HFO-1234ze did not exceed exposure with HFA-134a. Additionally, Cmax was increased for all BGF components with HFO-1234ze when using versus not using a spacer, with the largest increases observed among participants with the lowest exposure when not using a spacer, likely due to poor inhalation technique. No new safety findings, and no deaths or serious adverse events, occurred during the study. Implications: These findings provide evidence that may help to support the future use of HFO-1234ze propellant in BGF pMDIs. (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Hitesh Pandya reports a relationship with AstraZeneca that includes: employment and equity or stocks. Mehul Patel reports a relationship with AstraZeneca that includes: employment and equity or stocks. Michael Gillen reports a relationship with AstraZeneca that includes: contract employment and equity or stocks. Jitendar Reddy reports a relationship with AstraZeneca that includes: employment and equity or stocks. Artur Bednarczyk reports a relationship with AstraZeneca that includes: employment and equity or stocks. Marek Kokot reports a relationship with AstraZeneca that includes employment. Yubo Tan reports a relationship with AstraZeneca that includes: employment and equity or stocks. Maria Heijer reports a relationship with AstraZeneca that includes: employment and equity or stocks. Magdalena Andersson reports a relationship with AstraZeneca that includes: employment and equity or stocks. David Petullo reports a relationship with AstraZeneca that includes employment. Mandeep Jassal reports a relationship with AstraZeneca that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. |
| Contributed Indexing: | Keywords: AeroChamber Plus Flow-Vu® spacer device; Budesonide/glycopyrronium/formoterol fumarate dihydrate; Hydrofluoroolefin-1234ze; Next-generation propellant; Pharmacokinetics; Pressurized metered-dose inhaler |
| Substance Nomenclature: | V92SO9WP2I (Glycopyrrolate) 0 (Hydrocarbons, Fluorinated) 51333-22-3 (Budesonide) 0 (Aerosol Propellants) R40P36GDK6 (apaflurane) W34SHF8J2K (Formoterol Fumarate) 0 (Drug Combinations) 0 (Bronchodilator Agents) 0 (Ethanolamines) 0 (Fluorocarbons) |
| Entry Date(s): | Date Created: 20251204 Date Completed: 20260118 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.clinthera.2025.10.011 |
| PMID: | 41344973 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!