Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD

Rongchang Chen, Nanshan Zhong, Hao-Yan Wang, Li Zhao, Xiaodong Mei, Zhiqiang Qin, Juan Huang, Pryseley N Assam, Andrea Maes, Shahid Siddiqui, Ubaldo J Martin, Colin Reisner, Rongchang Chen, Nanshan Zhong, Hao-Yan Wang, Li Zhao, Xiaodong Mei, Zhiqiang Qin, Juan Huang, Pryseley N Assam, Andrea Maes, Shahid Siddiqui, Ubaldo J Martin, Colin Reisner

Abstract

Background: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4.

Methods: In this randomized, double-blind, placebo-controlled, parallel-group Phase III 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 (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study.

Results: Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all P≤0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group.

Conclusion: GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China.

Keywords: COPD; LAMA/LABA; bronchodilator; co-suspension delivery technology; exacerbations.

Conflict of interest statement

RC is an advisory committee member and speaker for AstraZeneca. NZ has received consultancy and lecture fees from Boehringer Ingelheim and Novartis and was on the advisory board of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee. XM and ZQ are speakers for AstraZeneca. JH and PNA are employees of AstraZeneca Shanghai, People's Republic of China. AM, SS, UJM, and CR are employees of AstraZeneca, with stock options. The authors report no other conflicts of interest in this work.

© 2020 Chen et al.

Figures

Figure 1
Figure 1
Patient disposition (all patients randomized in China). Abbreviations: FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GP, glycopyrrolate; MDI, metered dose inhaler.
Figure 2
Figure 2
Least squares mean change (±SE) from baseline in morning pre-dose trough FEV1 over 24 weeks (China ITT population). Note: Morning pre-dose trough FEV1 over 24 weeks was based on assessments at Weeks 2, 4, 8, 12, 16, 20, and 24. Abbreviations: FEV1, forced expiratory volume in 1 second; FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GP, glycopyrrolate; ITT, intent-to-treat; LSM, least squares mean; MDI, metered dose inhaler; SE, standard error.
Figure 3
Figure 3
Kaplan–Meier curves for (A) time to first moderate or severe COPD exacerbationa and (B) time to first CIDb (both China ITT population). Notes:aTime to first moderate or severe exacerbation (weeks) = (date of first COPD exacerbation – first treatment administration date + 1)/7. bTime to CID (weeks) = (date of CID – first treatment administration date + 1)/7. Abbreviations: CID, clinically important deterioration; COPD, chronic obstructive pulmonary disease; FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GP, glycopyrrolate; ITT, intent-to-treat; MDI, metered dose inhaler.

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