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.

Abstract

BackgroundThe 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 MethodsPINNACLE-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 <10 and exacerbation history in the previous year (none/one not requiring hospitalization). Endpoints evaluated were change from baseline in morning pre-dose trough forced expiratory volume in 1 second (FEV1), peak change from baseline in FEV1 within 2 hrs post-dose, and adverse events (AEs).ResultsThe 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.ConclusionGFF 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.