P6 Relative lung availability and total systemic exposure after inhalation of medium or high strength doses of beclometasone dipropionate/formoterol fumarate, formulated as pMDI with a next generation propellant

<h3>Background</h3> Growing concern around the global warming potential (GWP) of hydrofluoroalkane 134a (HFA-134a) propellant used in pressurized metered dose inhaler (pMDI) for asthma and COPD has prompted research into alternatives like HFA-152a, with a significantly lower GWP. A new formulation of CHF1535 [beclometasone dipropionate (BDP)/formoterol fumarate (FF)] 100/6 µg medium strength (MS) and 200/6 µg high strength (HS) has been developed with HFA-152a. Bioequivalence with CHF1535 HFA-134a marketed formulation should be demonstrated for BDP, B17MP (active metabolite of BDP) and Formoterol. <h3>Methods</h3> Two single-dose, double-blind, randomized, 4-way crossover studies with CHF1535 MS or HS were conducted in healthy volunteers, administered with a single dose of 4 inhalations of each formulation with HFA-152a or HFA-134a, with and without the use of the AeroChamber Plus^® spacer. Primary PK endpoints were C_max, AUC_0-t and t_max for all analytes and AUC_{0–30 min} for Formoterol only, to assess lung availability and systemic effect. Safety was monitored. <h3>Results</h3> The 90% confidence intervals of all PK parameter ratios between HFA-152a and HFA-134a for lung availability and total systemic exposure were within the bioequivalence acceptance interval (80.00–125.00%) for both strengths, with and without the spacer. There was no shift in median t_max. No safety signals were observed. <h3>Conclusions</h3> Therapeutic equivalence between the two formulations was demonstrated, supporting the timely introduction of therapeutic options enabling a seamless transition for patients, while minimizing climate impact.