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

Background: The 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 methods: PINNACLE-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).

Results: The 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.

Conclusion: GFF 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.

Keywords: COPD; bronchodilator; co-suspension delivery technology; lung function; muscarinic antagonist; β2-agonist.

Conflict of interest statement

FJM reports personal fees and non-financial support from American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, Chiesi, Concert, Continuing Education, Gala, Genentech, GlaxoSmithKline, Inova Fairfax Health System, Miller Communications, National Association for Continuing Education, Novartis, Pearl – a member of the AstraZeneca Group, PeerView Communications, Prime Communications, Puerto Rican Respiratory Society, Roche, Sunovion, and Theravance; non-financial support from ProterixBio; personal fees from American Thoracic Society, Columbia University, Haymarket Communications, Integritas, inThought Research, MD Magazine, Methodist Hospital Brooklyn, New York University, Teva, Unity, UpToDate, WebMD/MedScape, and Western Connecticut Health Network; and grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and National Institutes of Health. KFR reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi Pharmaceuticals, InterMune, Novartis, Sanofi, and Teva; and grants from the Ministry of Education and Science, Germany. 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. MJ, UJM, and CR are employees of AstraZeneca and hold stock and/or stock options in the company. The authors report no other conflicts of interest in this work.

© 2020 Martinez et al.

Figures

Figure 1

Study Flow Diagram for GOLD Category A Patients in PINNACLE-1, -2, and -4. Notes: N indicates the number of GOLD category A patients in each treatment arm. aThe open-label tiotropium bromide 18 μg DPI treatment arm was only included in PINNACLE-1. Abbreviations: DPI, dry-powder inhaler; FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GP, glycopyrrolate; MDI, metered dose inhaler.

Figure 2

Change from Baseline in Morning Pre-dose Trough FEV1 for the Pooled PINNACLE-1, -2, and -4 Studies in GOLD 2017 Category A Patients (ITT Population). Note: Error bars represent standard error. Abbreviations: FEV1, forced expiratory volume in 1 second; FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GP, glycopyrrolate; ITT, intent-to-treat; LSM, least squares mean; MDI, metered dose inhaler.

Figure 3

Peak Change from Baseline in FEV1 Within 2 hrs Post-dose for the Pooled PINNACLE-1, -2, and -4 Studies in GOLD 2017 Category A Patients (ITT Population). Note: Error bars represent standard error. Abbreviations: FEV1, forced expiratory volume in 1 second; FF, formoterol fumarate; GFF, glycopyrrolate/formoterol fumarate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; GP, glycopyrrolate; ITT, intent-to-treat; LSM, least squares mean; MDI, metered dose inhaler.