Published in:
Open Access
01-12-2017 | Research
A randomized, seven-day study to assess the efficacy and safety of a glycopyrrolate/formoterol fumarate fixed-dose combination metered dose inhaler using novel Co-Suspension™ Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease
Authors:
Colin Reisner, Leonardo M. Fabbri, Edward M. Kerwin, Charles Fogarty, Selwyn Spangenthal, Klaus F. Rabe, Gary T. Ferguson, Fernando J. Martinez, James F. Donohue, Patrick Darken, Earl St. Rose, Chad Orevillo, Shannon Strom, Tracy Fischer, Michael Golden, Sarvajna Dwivedi
Published in:
Respiratory Research
|
Issue 1/2017
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Abstract
Background
Long-acting muscarinic antagonist/long-acting β2-agonist combinations are recommended for patients whose chronic obstructive pulmonary disease (COPD) is not managed with monotherapy. We assessed the efficacy and safety of glycopyrrolate (GP)/formoterol fumarate (FF) fixed-dose combination delivered via a Co-Suspension™ Delivery Technology-based metered dose inhaler (MDI) (GFF MDI).
Methods
This was a Phase IIb randomized, multicenter, placebo-controlled, double-blind, chronic-dosing (7 days), crossover study in patients with moderate-to-very severe COPD (
NCT01085045). Treatments included GFF MDI twice daily (BID) (GP/FF 72/9.6 μg or 36/9.6 μg), GP MDI 36 μg BID, FF MDI 7.2 and 9.6 μg BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 μg BID or tiotropium DPI 18 μg once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV
1 AUC
0–12) on Day 7 relative to baseline FEV
1. Secondary endpoints included pharmacokinetics and safety.
Results
GFF MDI 72/9.6 μg or 36/9.6 μg led to statistically significant improvements in FEV1 AUC0–12 after 7 days’ treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p ≤ 0.0002). GFF MDI 36/9.6 μg was non-inferior to GFF MDI 72/9.6 μg and monocomponent MDIs were non-inferior to open-label comparators. Pharmacokinetic results showed glycopyrrolate and formoterol exposure were decreased following administration via fixed-dose combination versus monocomponent MDIs; however, this was not clinically meaningful. GFF MDI was well tolerated.
Conclusions
GFF MDI 72/9.6 μg and 36/9.6 μg BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.
Trial registration
ClinicalTrials.gov
NCT01085045. Registered 9 March 2010.