Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Lung Function versus Monotherapies in GOLD Category A Patients with COPD: Pooled Data from the Phase III PINNACLE Studies

Fernando J Martinez,¹ Klaus F Rabe,² Brian J Lipworth,³ Samir Arora,⁴ Martin Jenkins,⁵ Ubaldo J Martin,⁶ Colin Reisner<sup>6,7

1</sup>Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA; ²Department of Pneumonology, LungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; ³Division of Molecular and Clinical Medicine, Scottish Centre for Respiratory Research, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK; ⁴Aventiv Research Inc., Columbus, OH, USA; ⁵Global Medicines Development, AstraZeneca, Cambridge, UK; ⁶Research and Development, AstraZeneca, Gaithersburg, MD, USA; ⁷R&D Biopharmaceuticals, AstraZeneca, Morristown, NJ, USA

Correspondence: Fernando J Martinez
Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E 68th Street, Room M-522, Box 130, New York, NY 10065, USA
Tel +1646 962 2748
Email fjm2003@med.cornell.edu

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends a short-acting bronchodilator or single long-acting bronchodilator as an initial pharmacological treatment for GOLD category A patients with COPD. We pooled data from the PINNACLE-1, -2, and -4 studies to evaluate the efficacy and safety of the dual bronchodilator fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, in GOLD category A patients with moderate-to-very severe COPD.
Materials and Methods: PINNACLE-1, -2, and -4 were Phase III, randomized, double-blind, parallel-group, multicenter studies (NCT01854645, NCT01854658, and NCT02343458). Patients received 24 weeks’ treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI twice daily. GOLD category A patients were identified based on a COPD Assessment Test score of 1), peak change from baseline in FEV₁ within 2 hrs post-dose, and adverse events (AEs).
Results: The pooled intent-to-treat population comprised 729 GOLD category A patients. GFF MDI significantly improved morning pre-dose trough FEV₁ at Week 24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences 54 mL, 62 mL, and 188 mL, respectively; all p≤0.0053), and peak FEV₁ at Week 24 versus GP MDI, FF MDI, and placebo MDI (LSM differences 124 mL, 104 mL, and 307 mL, respectively; all p<0.0001). Improvements over 24 weeks were comparable to at Week 24. The AE profile of GFF MDI in GOLD category A patients was similar to monocomponents and placebo MDI.
Conclusion: GFF MDI significantly improved lung function versus monocomponents and placebo MDI in GOLD category A patients with moderate-to-very severe COPD, with no unexpected safety findings.

Keywords: β₂-agonist, bronchodilator, COPD, co-suspension delivery technology, lung function, muscarinic antagonist