Evidence map›Paper›PMID 41677208›Full record

Trial reportTherapeutic advances in respiratory disease

Bioequivalence of budesonide/glycopyrrolate/formoterol fumarate with a next-generation propellant versus hydrofluoroalkane-134a in healthy adults: phase I, randomized, double-blind, single-dose, partial-replicate, three-way cross-over lung exposure and total systemic exposure studies.

Artur Bednarczyk, Magnus Aurivillius, Mandeep Jassal, Mihir Shah, Ibrahim Raphiou, David Petullo, John Xu, Maria Heijer, Klementyna Sychowicz, Kathryn Collison and 6 more

2 registry-linked trialsAbstract readRandomized Controlled TrialClinical Trial, Phase IComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Therapeutic advances in respiratory disease. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05477108 phase1completednot on this map

A Phase I, Randomized, Double-blind, Single-dose, Partial Replicate, 3-way Cross-over Study to Assess the Lung Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA

TypeinterventionalSponsorAstraZenecaRan2022 to 2023Enrolled108ConditionsChronic Obstructive Pulmonary DiseaseArmsTreatment A (BGF MDI HFO with oral activated charcoal), Treatment B (BGF MDI HFA with oral activated charcoal)
NCT05569421 phase1completednot on this map

A Phase I, Randomized, Double-blind, Single-dose, Partial-replicate, 3-way Cross-over Study to Assess the Total Systemic Exposure Bioequivalence of Budesonide, Glycopyrronium, and Formoterol Delivered by BGF MDI HFO Compared With BGF MDI HFA

TypeinterventionalSponsorAstraZenecaRan2022 to 2023Enrolled108ConditionsChronic Obstructive Pulmonary DiseaseArmsTreatment A: BGF MDI HFO, Treatment B: BGF MDI HFA
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Artur BednarczykRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca Pharma Poland, Warsaw, Poland.
Magnus AurivilliusRespiratory and Immunology, Global Patient Safety, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0003-4660-5040
Mandeep JassalRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Mihir ShahRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Ibrahim RaphiouRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca, Durham, NC, USA.
David PetulloRespiratory and Immunology, Biometrics, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
John XuRespiratory and Immunology, Biometrics, Biopharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
Maria HeijerIntegrated Bioanalysis, Clinical Pharmacology and Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Klementyna SychowiczRespiratory and Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca Pharma Poland, Warsaw, Poland.
Kathryn CollisonRespiratory and Immunology, Clinical Operations, Biopharmaceuticals R&D, AstraZeneca, Durham, NC, USA.
Carlos SilvaClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Jitendar ReddyClinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK.
David HanParexel, Glendale, CA, USA.
Ronald GoldwaterParexel, Baltimore, MD, USA.
Michael GillenCreek Lane PK, LLC, Waterford, VA, USA.
Mehul PatelRespiratory & Immunology, Clinical Development, Biopharmaceuticals R&D, AstraZeneca, Academy House, 136 Hills Road, Cambridge CB2 8PA, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHydrofluoroolefin-1234ze (HFO-1234ze) is a next-generation propellant with 99.9% lower global warming potential (GWP) than hydrofluoroalkane-134a (HFA-134a).

objectivesWe report systemic and lung exposure bioequivalence for budesonide/glycopyrrolate/formoterol fumarate (BGF) components with HFO-1234ze versus HFA-134a.

designThese phase I, randomized, double-blind, single-dose, 3-way cross-over trials in healthy adults included three phases (screening; three single-dose treatment periods with 3- to 7-day washouts; follow-up).

methodsParticipants were randomized to four BGF inhalations (160/9/4.8 µg/actuation) with test (HFO-1234ze) or reference (HFA-134a) treatments in one of three sequences, with HFA-134a administered during two of the three treatment periods. For lung exposure, oral activated charcoal was administered before and after treatment. Bioequivalence was considered established if the 90% confidence interval (CI) for the geometric mean ratio (GMR) was within 80%-125% (or expanded limits, if appropriate) for maximum plasma concentration (Cmax), area under the plasma concentration-curve from time zero to the last quantifiable concentration (AUClast) and AUC from time zero to infinity (AUCinf; US approach only).

resultsBioequivalence criteria were met across BGF components. The 90% CI for the GMR was within 80%-125% (or expanded limits) for HFO-1234ze versus HFA-134a, for systemic (GMR: Cmax, 85.41-99.29; AUClast, 95.74-102.48; AUCinf, 90.72-102.58) and lung (GMR: Cmax, 93.39-104.24, AUClast, 97.02-107.76; AUCinf, 101.45-112.22) exposure. No serious adverse events were reported.

conclusionTotal systemic and lung exposure to all BGF components met bioequivalence criteria for HFO-1234ze versus HFA-134a, with no new or unexpected safety findings. The near-zero GWP HFO-1234ze propellant is a viable replacement for HFA-134a.

trial registrationNCT05569421 (clinicaltrials.gov/study/NCT05569421) and NCT05477108 (clinicaltrials.gov/study/NCT05477108).

Indexed as

Aerosol PropellantsBronchodilator AgentsBudesonideFormoterol FumarateGlycopyrrolateHydrocarbons, FluorinatedLungAdministration, InhalationAdolescentAdultArea Under CurveCross-Over StudiesDouble-Blind MethodDrug CombinationsFemaleFluorocarbonsAerosol PropellantsapafluraneBronchodilator AgentsBudesonideDrug CombinationsFluorocarbonsFormoterol FumarateGlycopyrrolateHydrocarbons, FluorinatedbioequivalenceCOPDglobal warming potentialhydrofluoroolefin-1234zenext-generation propellant

Identifiers

PMID41677208
PMCPMC12901903

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.