Safety of budesonide/glycopyrronium/formoterol fumarate dihydrate delivered by HFO-1234ze versus HFA-134a in chronic obstructive pulmonary disease: a phase 3, multi-site, randomised, double-blind, parallel-group, active-comparator study
Bibliographic record
Abstract
Background: Pressurised metered dose inhalers (pMDIs) contain a hydrofluorocarbon propellant, such as hydrofluoroalkane-134a (HFA-134a), which is known to have global warming potential (GWP). Transitioning pMDIs to propellants with lower GWP will reduce the environmental impact of pMDIs. This study assessed the safety of a near-zero GWP propellant, hydrofluoroolefin-1234ze (HFO-1234ze), compared with HFA-134a when used in the delivery of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) in participants with chronic obstructive pulmonary disease (COPD). The results of this study advance our understanding of the safety of HFO-1234ze compared with HFA-134a. Methods: This phase 3, double-blind, parallel-group study (ClinicalTrials.govNCT05573464) across 9 countries (Argentina, Bulgaria, Canada, Germany, Mexico, Poland, Turkey, the United Kingdom, the United States) included participants (aged 40-80 years) with physician-diagnosed COPD using dual or triple inhaled maintenance therapies, COPD Assessment Test score ≥10, ≥10 pack-years smoking history, and no comorbid diagnosis of asthma or other clinically significant diseases impacting study outcomes. Participants were randomised (1:1) to receive either BGF HFO-1234ze or BGF HFA-134a (two inhalations of 160/7·2/5·0 μg twice daily) for 12 weeks in the main safety analysis set (or 52 weeks [first 120 participants per treatment]). Safety endpoints included the incidence of adverse events (AEs), measures of vital signs, clinical laboratory tests, and electrocardiograms. Findings: Participants were recruited between 27 September 2022 and 19 May 2023. A total of 874 participants were screened. Of 558 treated participants (mean [standard deviation] age, 67·0 [7·4] years; male, 315 [56·5%]) in the 12-week safety analysis set, 280 received BGF HFO-1234ze, and 278 received BGF HFA-134a. The AE incidence was balanced between formulations in the 12-week (HFO-1234ze, 124 [44·3%]; HFA-134a, 114 [41·0%]) and 52-week (HFO-1234ze, 80 [66·7%]; HFA-134a, 94 [78·3%]) safety analysis sets. Interpretation: These findings support the potential for HFO-1234ze to replace HFA-134a in pMDIs containing BGF, which could be evaluated further in a real-world setting. Funding: The study was supported by AstraZeneca.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".