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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 teacher head, 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".