A Randomized, Double-Blind, Double-Dummy Study of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Relative to Umeclidinium/Vilanterol Dry Powder Inhaler in COPD

Adv Ther. 2019 Sep;36(9):2434-2449. doi: 10.1007/s12325-019-01015-3. Epub 2019 Jul 2.


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.

Keywords: Bronchodilators; Chronic obstructive pulmonary disease; LABA; LAMA; Respiratory.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Aged
  • Benzyl Alcohols / administration & dosage*
  • Bronchodilator Agents / therapeutic use
  • Chlorobenzenes / administration & dosage*
  • Double-Blind Method
  • Dry Powder Inhalers / methods*
  • Female
  • Forced Expiratory Volume / drug effects
  • Formoterol Fumarate / administration & dosage*
  • Glycopyrrolate / administration & dosage*
  • Humans
  • Male
  • Metered Dose Inhalers / statistics & numerical data*
  • Middle Aged
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Respiratory Function Tests
  • Treatment Outcome


  • Benzyl Alcohols
  • Bronchodilator Agents
  • Chlorobenzenes
  • Muscarinic Antagonists
  • vilanterol
  • Glycopyrrolate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT03162055
  • figshare/10.6084/m9.figshare.8229164