Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials

Background To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. Methods Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 hours (AUC 0–4h ) after nebulised 99m Tc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV 1 (litres), 15 minutes post dose (95% confidence intervals [CI]: lower limit >−10%, upper limit >0%). Both studies assessed safety. Results In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC 0–4h geometric mean ratio [90% CI]: 1.00 [0.99,1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV 1 at 15 minutes: −0.37% [HFA-152a] vs −0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [−3.61,4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. Conclusion HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.