A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD.

Abstract

Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, is the only approved fixed-dose combination long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) delivered via MDI. Direct comparisons of GFF MDI versus other LAMA/LABAs have not previously been performed. We assessed the efficacy and safety of GFF MDI relative to umeclidinium/vilanterol dry powder inhaler (UV DPI) in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). In this phase IIIb randomized, double-blind, double-dummy, multicenter, 24-week study, patients received GFF MDI 18/9.6μg (equivalent to glycopyrronium/formoterol fumarate dihydrate 14.4/10μg; two inhalations per dose, twice-daily; n = 559) or UV DPI 62.5/25μg (one inhalation, once-daily; n = 560). Primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in 1s (FEV1) and peak change from baseline in FEV1 within 2h post-dose, both over 24weeks. Additional lung function, symptom and safety endpoints were also assessed. For the primary endpoints, GFF MDI was non-inferior to UV DPI (using a margin of - 50mL) for peak FEV1 (least squares mean [LSM] difference - 3.4mL, 97.5% confidence interval [CI] - 32.8, 25.9) but not for trough FEV1 (LSM difference - 87.2mL; - 117.0, - 57.4). GFF MDI was nominally superior to UV DPI for onset of action (p < 0.0001) and was nominally non-inferior to UV DPI for all symptom endpoints (Transition Dyspnea Index focal score, Early Morning/Night-Time Symptoms COPD instrument scores, and COPD Assessment Test score). Exacerbation and safety findings were similar between groups. Over 24weeks of treatment, GFF MDI was non-inferior to UV DPI for peak FEV1, but not for morning pre-dose trough FEV1. GFF MDI had a faster onset of action versus UV DPI. There were no clinically meaningful differences between treatments in symptom endpoints. Both treatments were well tolerated with similar safety profiles. NCT03162055 (Clinicaltrials.gov) FUNDING: AstraZeneca.