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Int J Chron Obstruct Pulmon Dis. 2018 Sep 26;13:2969-2984. doi: 10.2147/COPD.S171835. eCollection 2018.

Improved lung function and patient-reported outcomes with co-suspension delivery technology glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a randomized Phase III study conducted in Asia, Europe, and the USA.

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Scottish Centre for Respiratory Research, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK,
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Itabashi Hospital, Nihon University School of Medicine, Itabashi, Tokyo, Japan.
Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan.
Aventiv Research Inc., Columbus, OH, USA.
Pearl - a member of the AstraZeneca group, Morristown, NJ, USA.
AstraZeneca, Gaithersburg, MD, USA.



COPD is a major global cause of mortality and morbidity. PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD.


In this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI (all twice daily) for 24 weeks. Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed.


Of the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2 years, 74.1% male, and 40.2% Asian). GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72 mL, respectively; all P<0.0001). GFF MDI also significantly improved other lung function endpoints vs placebo MDI, GP MDI, and FF MDI and patient-reported outcomes vs placebo MDI and GP MDI. A larger proportion of patients treated with GFF MDI achieved the minimum clinically important difference in Transition Dyspnea Index score vs GP MDI and placebo MDI and in St George's Respiratory Questionnaire score vs placebo MDI. Adverse event rates were similar across treatment groups.


These results demonstrated the efficacy of GFF MDI in patients with moderate-to-very severe COPD. GFF MDI was well tolerated, with a safety profile commensurate with long-acting bronchodilators.


COPD; bronchodilator; co-suspension delivery technology; muscarinic antagonist; β2-agonist

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Disclosure BJL is one of a number of co-investigators on an AstraZeneca- sponsored grant received by the University of Dundee to support genomic studies in COPD. He has also received speaker fees from AstraZeneca; payment for consulting and speaking from Boehringer Ingelheim and Chiesi; grant support from Boehringer Ingelheim, Chiesi, and Janssen; advisory board and speaker fees from Teva; and consulting fees from Sandoz, Cipla, Dr Reddys, and Lupin. DJC is supported by the National Institute for Health Research (NIHR) Barts Biomedical Research Center and received a grant from Pearl – a member of the AstraZeneca group, for normal recruitment of patients. YG received payment from AstraZeneca for medical institution costs for the clinical study and has received speaker fees from AstraZeneca, Boeh-ringer Ingelheim Japan Co., Ltd, and Kyorin Pharmaceutical Co., Ltd. NZ has received consultancy and lecture fees from Boehringer Ingelheim and Novartis and was on the advisory board of the GOLD committee. KN and SA report no conflicts of interest in this work. RC is an advisory committee member and speaker for AstraZeneca. AM is an employee of Pearl – a member of the AstraZeneca Group. SS and UJM are employees of AstraZeneca, with stock options. CR is an employee of Pearl – a member of the AstraZeneca group and an employee of AstraZeneca.

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