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 (TM) Delivery Technology in patients with moderate-to-very severe chronic obstructive pulmonary disease

作者：Reisner Colin; Fabbri Leonardo M; Kerwin Edward M; Fogarty Charles; Spangenthal Selwyn; Rabe Klaus F; Ferguson Gary T; Martinez Fernando J; Donohue James F; Darken Patrick; St Rose Earl; Orevillo Chad; Strom Shannon; Fischer Tracy; Golden Michael; Dwivedi Sarvajna

来源：Respiratory Research, 2017, 18(1): 8.

DOI：10.1186/s12931-016-0491-8

• COPD
• LAMA
• LABA
• Lung function
• Bronchodilators
• COPD maintenance
• Co-Suspension (TM) Delivery Technology
• Metered dose inhaler

Background: Long-acting muscarinic antagonist/long-acting beta(2)-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 (TM) 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 mu g or 36/9.6 mu g), GP MDI 36 mu g BID, FF MDI 7.2 and 9.6 mu g BID, placebo MDI, and open-label formoterol dry powder inhaler (FF DPI) 12 mu g BID or tiotropium DPI 18 mu g once daily. The primary endpoint was forced expiratory volume in 1 s area under the curve from 0 to 12 h (FEV1 AUC(0-12)) on Day 7 relative to baseline FEV1. Secondary endpoints included pharmacokinetics and safety.
Results: GFF MDI 72/9.6 mu g or 36/9.6 mu g led to statistically significant improvements in FEV1 AUC(0-12) after 7 days' treatment versus monocomponent MDIs, placebo MDI, tiotropium, or FF DPI (p <= 0.0002). GFF MDI 36/9.6 mu g was non-inferior to GFF MDI 72/9.6 mu g 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 mu g and 36/9.6 mu g BID improve lung function and are well tolerated in patients with moderate-to-very severe COPD.

• 出版日期2017-1-6