Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease.

Background: PINNACLE-4 evaluated the efficacy and safety of the long-acting muscarinic antagonist/long-acting β ₂ -agonist fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in patients from Asia, Europe, and the USA with moderate-to-very severe chronic obstructive pulmonary disease (COPD). This pre-specified analysis included Japanese patients in PINNACLE-4.
Methods: In this double-blind randomized study (NCT02343458), patients received GFF MDI (18/9.6 μg), glycopyrrolate (GP) MDI (18 μg), formoterol fumarate (FF) MDI (9.6 μg), or placebo MDI twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV ₁ ) over Weeks 12-24. Secondary lung function endpoints, patient-reported outcomes, and safety were assessed. The Japanese subpopulation (n = 150) analyses were exploratory.
Results: GFF MDI improved change from baseline in morning pre-dose trough FEV ₁ over Weeks 12-24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences [95% confidence interval]: 69 [8-131], 60 [-1 to 121], and 275 [180-370] mL, respectively). GFF MDI numerically improved Transition Dyspnea Index focal score and change from baseline in St George's Respiratory Questionnaire total score versus placebo MDI (LSM differences 0.19 and -3.78, respectively). Treatment-related adverse events occurred in ≤4.5% of patients in any treatment group.
Conclusions: GFF MDI improved lung function versus monocomponents and placebo MDI in the Japan subpopulation of PINNACLE-4. The efficacy and safety results were generally consistent with those of the global study population, supporting the use of GFF MDI in Japanese patients with moderate-to-very severe COPD.
Competing Interests: Conflict of interest YG has received fees from AstraZeneca, Boehringer Ingelheim Japan Co. Ltd and Kyorin Pharmaceutical Co. KN and KS have no financial conflicts of interest to disclose. AM, NH, HH, CR, and UJM are employees of AstraZeneca and hold stock and/or stock options in the company. SS is an employee of AstraZeneca.
(Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)