François Maltais1, Gary T Ferguson2, Gregory J Feldman3, Gaëtan Deslee4, Arnaud Bourdin5, Harald Fjällbrant6, Agnieszka Siwek-Posłuszna7, Martin A Jenkins8, Ubaldo J Martin9. 1. Centre de Recherche, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada. Francois.Maltais@med.ulaval.ca. 2. Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA. 3. S. Carolina Pharmaceutical Research, Spartanburg, SC, USA. 4. Hôpital Maison Blanche, INSERM U1250, Service des Maladies Respiratoires, CHU de Reims, Reims, France. 5. CHU Montpellier, PhyMedExp, INSERM, CNRS, Université de Montpellier, Montpellier, France. 6. AstraZeneca Gothenburg, Mölndal, Sweden. 7. AstraZeneca, Warsaw, Poland. 8. AstraZeneca, Cambridge, UK. 9. AstraZeneca, Gaithersburg, MD, USA.
Abstract
INTRODUCTION:Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, is the only approved fixed-dose combination long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) delivered via MDI. Direct comparisons of GFF MDI versus other LAMA/LABAs have not previously been performed. We assessed the efficacy and safety of GFF MDI relative to umeclidinium/vilanterol dry powder inhaler (UV DPI) in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: In this phase IIIb randomized, double-blind, double-dummy, multicenter, 24-week study, patients received GFF MDI 18/9.6 μg (equivalent to glycopyrronium/formoterol fumarate dihydrate 14.4/10 μg; two inhalations per dose, twice-daily; n = 559) or UV DPI 62.5/25 μg (one inhalation, once-daily; n = 560). Primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) and peak change from baseline in FEV1 within 2 h post-dose, both over 24 weeks. Additional lung function, symptom and safety endpoints were also assessed. RESULTS: For the primary endpoints, GFF MDI was non-inferior to UV DPI (using a margin of - 50 mL) for peak FEV1 (least squares mean [LSM] difference - 3.4 mL, 97.5% confidence interval [CI] - 32.8, 25.9) but not for trough FEV1 (LSM difference - 87.2 mL; - 117.0, - 57.4). GFF MDI was nominally superior to UV DPI for onset of action (p < 0.0001) and was nominally non-inferior to UV DPI for all symptom endpoints (Transition Dyspnea Index focal score, Early Morning/Night-Time Symptoms COPD instrument scores, and COPD Assessment Test score). Exacerbation and safety findings were similar between groups. CONCLUSIONS: Over 24 weeks of treatment, GFF MDI was non-inferior to UV DPI for peak FEV1, but not for morning pre-dose trough FEV1. GFF MDI had a faster onset of action versus UV DPI. There were no clinically meaningful differences between treatments in symptom endpoints. Both treatments were well tolerated with similar safety profiles. TRIAL REGISTRATION: NCT03162055 (Clinicaltrials.gov) FUNDING: AstraZeneca.
RCT Entities:
INTRODUCTION:Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, is the only approved fixed-dose combination long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) delivered via MDI. Direct comparisons of GFF MDI versus other LAMA/LABAs have not previously been performed. We assessed the efficacy and safety of GFF MDI relative to umeclidinium/vilanterol dry powder inhaler (UV DPI) in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: In this phase IIIb randomized, double-blind, double-dummy, multicenter, 24-week study, patients received GFF MDI 18/9.6 μg (equivalent to glycopyrronium/formoterol fumarate dihydrate 14.4/10 μg; two inhalations per dose, twice-daily; n = 559) or UV DPI 62.5/25 μg (one inhalation, once-daily; n = 560). Primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) and peak change from baseline in FEV1 within 2 h post-dose, both over 24 weeks. Additional lung function, symptom and safety endpoints were also assessed. RESULTS: For the primary endpoints, GFF MDI was non-inferior to UV DPI (using a margin of - 50 mL) for peak FEV1 (least squares mean [LSM] difference - 3.4 mL, 97.5% confidence interval [CI] - 32.8, 25.9) but not for trough FEV1 (LSM difference - 87.2 mL; - 117.0, - 57.4). GFF MDI was nominally superior to UV DPI for onset of action (p < 0.0001) and was nominally non-inferior to UV DPI for all symptom endpoints (Transition Dyspnea Index focal score, Early Morning/Night-Time Symptoms COPD instrument scores, and COPD Assessment Test score). Exacerbation and safety findings were similar between groups. CONCLUSIONS: Over 24 weeks of treatment, GFF MDI was non-inferior to UV DPI for peak FEV1, but not for morning pre-dose trough FEV1. GFF MDI had a faster onset of action versus UV DPI. There were no clinically meaningful differences between treatments in symptom endpoints. Both treatments were well tolerated with similar safety profiles. TRIAL REGISTRATION: NCT03162055 (Clinicaltrials.gov) FUNDING: AstraZeneca.
Authors: John R Hurst; Kevin Gruffydd-Jones; Mousumi Biswas; Deniz Guranlioglu; Martin Jenkins; Neda Stjepanovic; Arushi Bamrara Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-07-01
Authors: Afisi S Ismaila; Katrin Haeussler; Alexandrosz Czira; Vanita Tongbram; Mia Malmenäs; Jatin Agarwal; Maria Nassim; Marija Živković-Gojović; Yunrong Shen; Xinzhe Dong; Maria Duarte; Chris Compton; Claus F Vogelmeier; David M G Halpin Journal: Adv Ther Date: 2022-07-20 Impact factor: 4.070