• 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, and Sarvajna Dwivedi.
• Pearl Therapeutics Inc., 280 Headquarters Plaza, East Tower, 2nd Floor, Morristown, NJ, 07960, USA. creisner@pearltherapeutics.com.
• Resp Res. 2017 Jan 6; 18 (1): 8.

BackgroundLong-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).MethodsThis 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 (FEV1 AUC0-12) on Day 7 relative to baseline FEV1. Secondary endpoints included pharmacokinetics and safety.ResultsGFF 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.ConclusionsGFF 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 RegistrationClinicalTrials.gov NCT01085045 . Registered 9 March 2010.

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