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Mucociliary Clearance Following a Next-Generation Propellant Versus Hydrofluoroalkane-134a via Pressurized
Scott H Donaldson1, Kirby L Zeman1, Alan Bell2
1Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Background:
Pressurized metered-dose inhalers (pMDIs) are commonly used for respiratory disease treatment but contain propellants, such as hydrofluoroalkane-134a (HFA-134a), with global warming potential (GWP) that contribute to the climate emergency. To safeguard essential medicine access, it is crucial to transition to lower-GWP propellants, such as hydrofluoroolefin-1234ze (HFO-1234ze), which has 99% lower GWP than HFA-134a. In accordance with global regulatory requirements, this study was conducted to support the registration of pMDIs with HFO-1234ze.
Methods:
This randomized, double-blind, multicenter, two-way crossover study assessed the effects of HFO-1234ze versus HFA-134a on mucociliary clearance (MCC) in healthy participants aged 18-60 years. Participants received six inhalations twice daily of HFO-1234ze and HFA-134a in two 7-day (+3) intervention periods separated by a 7- to 14-day washout. The primary and secondary endpoints were change from period-specific baseline in average whole lung MCC (%) through 60 minutes (MCC60) and at 3 hours (MCC3h), respectively, measured via inhalation of 99mTc-labeled colloid and gamma camera imaging. Given significant baseline variability, a post hoc analysis of the primary endpoint assessed change from average baseline instead of period-specific baseline MCC60. Additional safety and tolerability measures were assessed.
Results:
Forty-five participants were screened; the Primary Analysis Set included 34 participants who completed both intervention periods. For the primary endpoint, change from period-specific baseline in MCC60 was negligible, with an estimated change (95% confidence interval [CI]) of -0.6% (-3.2%, 1.9%) for HFO-1234ze and 0.8% (-1.7%, 3.3%) for HFA-134a. The estimated least-squares mean difference (95% CI) between HFO-1234ze and HFA-134a was -1.4% (-5.8%, 2.9%). For the secondary endpoint, the estimated least-squares mean difference for change from period-specific baseline in MCC3h between HFO-1234ze and HFA-134a was -5.7% (-10.9%, -0.5%). There were no unexpected safety findings.
Conclusion:
There was no clinically relevant impact of HFO-1234ze versus HFA-134a on MCC in healthy participants.
Clinical Trial Registration Number:
NCT05755932.
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