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.

Gon, Yasuhiro; Nishi, Koichi; Sato, Kazuhiro; Maes, Andrea; Siddiqui, Shahid; Hayashi, Nobuya; Hirata, Hajime; Martin, Ubaldo J; Reisner, Colin

BACKGROUND PINNACLE-4 evaluated the efficacy and safety of the long-acting muscarinic antagonist/long-acting β2-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 (FEV1) 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 FEV1 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.