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

Int J Chron Obstruct Pulmon Dis. 2020 Jan 8:15:43-56. doi: 10.2147/COPD.S223638. eCollection 2020.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adrenergic beta-2 Receptor Agonists / therapeutic use*
  • Aged
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / adverse effects
  • China
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate / administration & dosage
  • Formoterol Fumarate / adverse effects
  • Formoterol Fumarate / therapeutic use*
  • Glycopyrrolate / adverse effects
  • Glycopyrrolate / therapeutic use*
  • Humans
  • Lung / drug effects*
  • Lung / physiopathology
  • Male
  • Metered Dose Inhalers*
  • Middle Aged
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / adverse effects
  • Muscarinic Antagonists / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Recovery of Function
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Drug Combinations
  • Muscarinic Antagonists
  • Glycopyrrolate
  • Formoterol Fumarate

Associated data

  • ClinicalTrials.gov/NCT02343458