Efficacy and safety of four doses of glycopyrrolate/formoterol fumarate delivered via a metered dose inhaler compared with the monocomponents in patients with moderate-to-severe COPD

Purpose: To determine the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 36/9.6, 36/7.2, 18/9.6, 9/9.6 mu g) using innovative co-suspension delivery technology, compared with glycopyrrolate (GP) MDI 36 mu g and formoterol fumarate (FF) MDI 9.6 mu g, in patients with moderate-to-severe COPD. Methods: In this Phase IIb, randomized, double-blind, balanced incomplete-block, two-period, cross-over study (NCT01349816), patients received treatment twice-daily for 7 days. The primary efficacy endpoint was forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC(0-12)) on Day 7. Secondary efficacy endpoints were peak change from baseline in FEV1 through 2 hours; time to onset of action (>= 10% improvement in mean FEV1); proportion of patients achieving >= 12% improvement in FEV1 on Day 1; peak change from baseline in inspiratory capacity (IC) on Days 1 and 7; change from baseline in morning pre-dose FEV1; peak change from baseline in FEV1 through 6 hours; and change from baseline in mean evening 12-hour post-dose trough FEV1 on Day 7. Safety was assessed. Results: All 185 randomized patients received treatment. All doses of GFF MDI significantly improved the primary endpoint compared with GP MDI 36 mu g (all P <= 0.0137). For peak change in FEV1 and IC and time to onset of action secondary endpoints, >= 2 doses of GFF MDI demonstrated superiority to GP MDI 36 mu g. No significant differences were observed between GFF MDI and FF MDI 9.6 mu g for primary and secondary endpoints. The incidence of adverse events was similar between treatments. Conclusion: While all doses of GFF MDI were superior to GP MDI 36 mu g for the primary endpoint, in this study neither superiority of GFF MDI to FF MDI 9.6 mu g nor a clear dose-response was observed. All treatments were well tolerated with no unexpected safety findings.