Effect of inhaled budesonide/formoterol fumarate dihydrate delivered via two different devices on lung function in patients with COPD and low peak inspiratory flow

Abstract

Background and aims: Low peak inspiratory flow (PIF) is common following severe exacerbations of chronic obstructive pulmonary disease (COPD). Patients with COPD and low PIF may be at risk of suboptimal delivery of inhaled therapies to the airways, especially when using devices such as dry powder inhalers (DPIs), which require greater inspiratory effort than metered dose inhalers (MDIs). We report the results from a 2-week crossover study evaluating the effects of inhaled dual therapy with budesonide/formoterol fumarate dihydrate with an MDI with a spacer versus a DPI in patients with COPD and low PIF.

Methods: This randomized, open-label, two-period (each 1 week in duration) crossover efficacy and safety study included patients with severe-to-very severe COPD and PIF < 50 L/min (NCT04078126). Patients were randomized 1:1 to twice-daily budesonide/formoterol fumarate dihydrate MDI (BFF MDI) 320/10 µg with a spacer for 1 week followed by twice-daily budesonide/formoterol fumarate dihydrate DPI (BUD/FORM DPI) 320/9 µg for 1 week, or the inverse. The primary endpoint was peak change from baseline in forced expiratory volume in 1 s (FEV1) within 4 h post-dose following 1 week of treatment. Other assessments included pre-dose lung function, pharmacokinetics, and safety, as assessed by adverse events.

Results: The modified intention-to-treat analysis set comprised 30 patients (mean age: 66.9 years; mean baseline FEV1: 766 mL; mean COPD assessment test score: 22.20). Following 1 week of treatment, both BFF MDI and BUD/FORM DPI improved mean [95% confidence interval (CI)] peak FEV1 4 h post-dose [256 (190, 322) mL and 274 (208, 340) mL, respectively]. No clinically meaningful difference between treatments was observed for any lung function endpoint. There were no unexpected safety findings.

Conclusion: Dual therapy with BFF MDI and with BUD/FORM DPI led to improvements in lung function in patients with severe-to-very severe COPD and low PIF.

Keywords: budesonide; chronic obstructive pulmonary disease; dry powder inhaler; formoterol fumarate dihydrate; inhaled dual therapy; metered dose inhaler; peak inspiratory flow.

Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.H. is an employee of Inamed Gmbh (part of Nuvisan Gmbh), which was contracted by AstraZeneca for this study. C.K. has a lung and bronchial medicine practice, including a study center in Frankfurt am Main, Germany and was contracted by AstraZeneca as a consultant research physician for this study. A.R. is an employee of Medsearch UK Limited and was contracted by AstraZeneca as a consultant research physician for this study. M.A. and M.J. are employees of AstraZeneca and own stock or stock options in the company.

Figures

Figure 1.

Study design. BFF MDI, budesonide/formoterol fumarate dihydrate metered dose inhaler; BUD/FORM DPI, budesonide/formoterol fumarate dihydrate DPI. aAdministered twice daily. bAdministered four times daily.

Figure 2.

Patient disposition. BFF MDI, budesonide/formoterol fumarate dihydrate metered dose inhaler; BUD/FORM DPI, budesonide/formoterol fumarate dihydrate dry powder inhaler; Cmax, maximum concentration; COVID-19, coronavirus disease 2019; mITT, modified intention-to-treat.

Figure 3.

Peak change from baseline in FEV1 within 4 h post-dose following 1 week of treatment (mITT analysis set). Data are presented as adjusted means; error bars depict 95% CI. The adjusted mean difference is calculated as BFF MDI minus BUD/FORM DPI. BFF MDI, budesonide/formoterol fumarate dihydrate metered dose inhaler; BUD/FORM DPI, budesonide/formoterol fumarate dihydrate dry powder inhaler; CI, confidence interval; FEV1, forced expiratory volume in 1 s; mITT, modified intention-to-treat.

Figure 4.

Geometric mean (a) budesonide and (b) formoterol fumarate plasma concentrations over time (pharmacokinetics analysis set).BFF MDI, budesonide/formoterol fumarate dihydrate metered dose inhaler; BUD/FORM DPI, budesonide/formoterol fumarate dihydrate dry powder inhaler. Data are presented as geometric mean; error bars depict the geometric standard deviation.