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.

• Authors: Fernando J Martinez, Klaus F Rabe, Brian J Lipworth, Samir Arora, Martin Jenkins, Ubaldo J Martin, Colin Reisner
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 15 Pg. 99-106 ( 2020) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 32021148 (Publication Type: Journal Article)
• Copyright: © 2020 Martinez et al.

Chemical References

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

Topics

• Administration, Inhalation
• Adrenergic beta-2 Receptor Agonists (administration & dosage, adverse effects, therapeutic use)
• Aged
• Bronchodilator Agents (administration & dosage, adverse effects, therapeutic use)
• Clinical Trials, Phase III as Topic
• Drug Combinations
• Female
• Forced Expiratory Volume
• Formoterol Fumarate (administration & dosage, adverse effects, therapeutic use)
• Glycopyrrolate (administration & dosage, adverse effects, therapeutic use)
• Humans
• Lung (drug effects, physiopathology)
• Male
• Metered Dose Inhalers
• Middle Aged
• Multicenter Studies as Topic
• Muscarinic Antagonists (administration & dosage, adverse effects, therapeutic use)
• Pulmonary Disease, Chronic Obstructive (diagnosis, drug therapy, physiopathology)
• Randomized Controlled Trials as Topic
• Recovery of Function
• Severity of Illness Index
• Time Factors
• Treatment Outcome