S61 Reducing the environmental impact of pressurized metered dose inhalers: relative bioavailability of budesonide/glycopyrronium/formoterol fumarate dihydrate with novel propellant formulations in healthy subjects

Abstract

<h3>Introduction and Objectives</h3> There is value in assessing whether it is possible to formulate metered dose inhaler (MDI) products using novel propellants with lower greenhouse gas potential than, and comparable pharmacokinetic (PK) parameters to, currently marketed MDIs. The objective of this study was to evaluate the relative bioavailabilities of the components in the fixed-dose combination of budesonide, glycopyrronium, and formoterol fumarate dihydrate (BGF) between three different propellant formulations of BGF MDI, 160/7.2/5 µg per actuation. <h3>Methods</h3> Healthy subjects aged 18 to 60 years were randomized into a single-blind, three-period, single-dose, single-centre, crossover study (NCT04600505). The study assessed three propellants: hydrofluoroolefin (HFO-1234ze; test), hydrofluorocarbon (HFC-152a; test) and hydrofluoroalkane (HFA-134a; marketed reference product, Trixeo Aerosphere^TM). The study included a screening period, three treatment periods and a follow-up. There was a washout period of 3 to 7 days between each dose. The primary PK parameters were the maximum observed plasma concentration (C_max) and the area under the plasma concentration curve from time zero to the last quantifiable analyte concentration (AUC_last). The study had low statistical power to demonstrate bioequivalence. <h3>Results</h3> Twenty-four healthy subjects were evaluable for PK assessments and completed the study. Systemic exposure to budesonide, glycopyrronium and formoterol from the test products, BGF MDI HFO-1234ze and BGF MDI HFC-152a, was comparable to the reference product, BGF MDI HFA-134a, for C_max and AUC_last (table 1). There were no reported serious adverse events or adverse events that led to treatment discontinuation during this study. No new safety signals were observed. <h3>Conclusions</h3> Systemic exposure to all BGF components was similar when delivered with either novel test propellant (HFO-1234ze and HFC-152a) relative to the reference propellant (HFA-134a) used in marketed BGF. The combination of BGF when administered as single doses in three different propellant formulations demonstrated an acceptable safety profile and was well tolerated in the studied population. Both novel, low global warming-potential propellants may be viable for use in a clinical setting; therefore, further investigation in larger studies is warranted. Please refer to page A210 for declarations of interest related to this abstract.