A32-08 Systemic Exposure Bioequivalence of Budesonide/Glycopyrrolate/Formoterol Fumarate Inhaler Components (320/36/9.6 µg/dose) With a Next Generation Propellant Versus Hydrofluoroalkane-134a

Rationale Hydrofluoroolefin-1234ze (HFO-1234ze) is a next-generation propellant with >99% lower global warming potential versus the widely used hydrofluoroalkane-134a (HFA-134a) propellant. This study assessed the bioequivalence of budesonide/glycopyrrolate/formoterol fumarate (BGF) [320/36/9.6 μg/dose] formulated with HFO-1234ze propellant versus BGF formulated with HFA-134a propellant delivered via pressurized metered-dose inhalers (pMDI). Methods A Phase 1, randomized, double-blind, single-dose, single-site, 3-way crossover study (NCT06723756) included healthy non-smoking participants aged 18-60 years with a BMI between 18-30 kg/m2. Randomized participants received BGF (160/18/4.8 μg/actuation, 2 inhalations as a single dose) with HFO-1234ze (test formulation), administered in one treatment period (Treatment A), or BGF HFA-134a (reference formulation) administered during two replicate treatment periods (Treatment B), in 1 of 3 treatment sequences (ABB, BAB, BBA). Primary pharmacokinetic endpoints for assessing total systemic exposure of the analytes of BGF components (budesonide, glycopyrronium, and formoterol) with HFO-1234ze versus HFA-134a included maximum observed plasma concentration (Cmax) and area under the plasma concentration curve (AUC) from time zero to the time of the last quantifiable concentration (AUClast). Bioequivalence was established if geometric mean ratios were within the 80-125% range, and the associated 90% confidence intervals met regulatory criteria. Safety and tolerability were also assessed. Results All 105 randomized participants (mean [standard deviation] age, 38.7 [9.0] years; male, 66.7%) were included in the analyses. Total systemic exposure of each BGF component based on Cmax and AUClast met bioequivalence criteria for HFO-1234ze relative to HFA-134a (Table). Adverse events (AEs) were reported in 6.7% of participants with BGF HFO-1234ze and in 10.5% and 2.9% of participants with BGF HFA-134a (replicates 1 and 2, respectively). No serious AEs, deaths or AEs leading to discontinuation were reported. Conclusions This study demonstrated total systemic bioequivalence of BGF HFO-1234ze to BGF HFA-134a (320/36/9.6 μg/dose). The results of this study support the transition of BGF HFA-134a to BGF HFO-1234ze in indications where a 36 µg dose of the long-acting muscarinic antagonist glycopyrrolate is applicable.