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
Received 24 February 2018
Accepted for publication 16 May 2018
Published 19 June 2018 Volume 2018:13 Pages 1965—1977
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Colin Reisner,1,2 James Pearle,3 Edward M Kerwin,4 Earl St Rose,1 Patrick Darken1
1Pearl – a member of the AstraZeneca Group, Morristown, NJ, USA; 2AstraZeneca, Gaithersburg, MD, USA; 3California Research Medical Group, Inc., Fullerton, CA, USA; 4Clinical Research Institute of Southern Oregon, Medford, OR, USA
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 μg) using innovative co‑suspension delivery technology, compared with glycopyrrolate (GP) MDI 36 μg and formoterol fumarate (FF) MDI 9.6 μg, 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 (AUC0–12) 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 μg (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 μg. No significant differences were observed between GFF MDI and FF MDI 9.6 μg 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 μg for the primary endpoint, in this study neither superiority of GFF MDI to FF MDI 9.6 μg nor a clear dose-response was observed. All treatments were well tolerated with no unexpected safety findings.
Keywords: bronchodilator, chronic obstructive pulmonary disease, co-suspension delivery technology, fixed-dose combination, LAMA/LABA, long-acting β2-agonist, long-acting muscarinic antagonist
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