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 h (AUC0‐4h) after nebulised 99mTc 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 FEV1 (litres), 15 min 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 (AUC0‐4h 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 FEV1 at 15 min: ‐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.