Abstract Rationale The next-generation propellant hydrofluoroolefin-1234ze (HFO-1234ze) is in development for pressurized metered-dose inhalers (pMDIs), having 99% lower global warming potential versus the widely used hydrofluoroalkane-134a (HFA-134a) propellant. We assessed the pharmacodynamic equivalence of budesonide/glycopyrrolate/formoterol fumarate (BGF) with HFO-1234ze versus BGF with HFA-134a on measures of lung function, and evaluated safety, in patients with COPD. Methods This randomized, double-blind, multi-center, 3-way crossover study (NCT06075095) included participants aged 40-80 years with an established clinical history of COPD as defined by ATS/ERS guidelines. Participants had a ratio of post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity 0.70, and post-bronchodilator FEV1 ≥40% and 80% predicted normal value. Randomized participants received the following treatments as a single dose via two pMDI inhalations twice-daily for 4 weeks: A) BGF HFO-1234ze 320/18/9.6 μg, B) BGF HFA-134a 320/18/9.6 μg, and C) placebo HFA-134a in one of six treatment sequences. Endpoints to assess equivalence of BGF HFO-1234ze versus BGF HFA-134a on lung function were the change from baseline in post-dose FEV1 area under the curve from 0 to 4 hours (FEV1 AUC0-4h; primary) and morning pre-dose trough FEV1 (secondary) at Day 29; equivalence was demonstrated if the two-sided 90% confidence intervals (CIs) for ratios of BGF HFO-1234ze/BGF HFA-134a were within 0.8-1.25 and 0.7-1.43, respectively. Confirmation of the effect of BGF on lung function required superiority of BGF HFA-134a versus placebo HFA-134a, evaluated as mean treatment differences in lung function endpoints, with a two-sided p 0.05. Safety was also assessed. Results 296 participants were randomized (age mean ± standard deviation, 64.1 ± 7.6 years; male, 59.1%). The effect of BGF was confirmed (p 0.001) for both lung function endpoints when comparing BGF HFA-134a versus placebo HFA-134a (Table, A). The changes from baseline in post-dose FEV1 AUC0-4 and morning pre-dose trough FEV1 at Day 29 were equivalent between BGF HFO-1234ze and BGF HFA-134a (Ratio 90% CI: 0.94 0.88, 1.00; 0.95 0.84, 1.08, respectively); Table, B. Adverse events (AEs) were balanced across treatments with no new safety findings with HFO-1234ze; AEs were observed in 20 participants (7.1%) with BGF HFO-1234ze; 30 (10.6%) with BGF HFA-134a; and 39 (13.8%) with placebo HFA-134a. Conclusion This study in patients with COPD demonstrated that lung function improvement with BGF HFO-1234ze was equivalent to BGF HFA-134a. The safety profiles were also comparable, thus confirming the established benefit-risk profile of BGF and supporting the transition from HFA-134a to HFO-1234ze in BGF pMDIs. This abstract is funded by: AstraZeneca
Camiolo et al. (Fri,) studied this question.