KRONOS: 24-week study of triple fixed-dose combination budesonide/glycopyrronium/formoterol (BGF) MDI via co-suspension delivery technology vs glycopyrronium/formoterol (GFF) MDI, budesonide/formoterol (BFF) MDI and BFF inhalation powder in COPD

Objectives: To assess treatment effects of BGF MDI, an ICS/LAMA/LABA fixed-dose combination (FDC), on lung function (primary objective), exacerbations, symptoms, quality of life and safety in subjects with moderate-to-very severe COPD. Methods: Subjects in this Phase III, double-blind, parallel study (NCT02497001) were randomized 2:2:1:1 to receive BGF metered dose inhaler (MDI) 320/14.4/10μg, GFF MDI 14.4/10μg, BFF MDI 320/10μg or open-label Symbicort ® Turbuhaler ® dry powder inhaler (BUD/FORM DPI) 400/12μg twice daily for 24 weeks. Results: BGF MDI significantly improved FEV 1 AUC 0−4 over 24 weeks vs BFF MDI and BUD/FORM DPI, and morning pre-dose trough FEV 1 vs GFF MDI and BFF MDI (Table). BGF MDI also significantly reduced exacerbation rates vs GFF MDI, and improved respiratory symptoms and quality of life vs GFF MDI and BFF MDI. BFF MDI was non-inferior to BUD/FORM DPI. No new or unexpected safety findings were observed. Conclusion: BGF MDI improved lung function compared with dual therapies, with significant reductions in exacerbation rates vs GFF MDI and a trend vs BFF MDI in patients with moderate-to-very severe COPD. All treatments were well tolerated.