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.
Omar S Usmani, Fernando J Martinez, Hitesh Pandya, Matthew Camiolo, Artur Bednarczyk, Kinga Kucz, Marek Kokot, Christer Gottfridsson, Magnus Aurivillius, Lars Pettersson, Jie Mei, Karin Skansen, Jennifer L Bell, David Petullo, Kathryn Collison, Patrik Bondarov, Mandeep Jassal, Mehul Patel
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引用次数: 0
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.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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