Lung Deposition of Inhaled Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide in Healthy Volunteers and Asthma: The STORM Study

Background: An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation.Methods: This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (Kr-81m) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 mu g radiolabeled using technetium-99 m [Tc-99m]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; Tc-99m aerosol C/P/Kr-81m gas C/P).Results: All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean +/- standard deviation intrapulmonary deposition was 25.50% +/- 6.81%, not significantly different to that in healthy volunteers (22.74% +/- 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 +/- 0.07 and 0.49 +/- 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 +/- 0.25 and 1.06 +/- 0.25, respectively, with sC/P ratios of 1.80 +/- 0.40 and 1.94 +/- 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated.Conclusions: This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition.Clinical Trial Registration number: NCT03795350.