A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids.

Abstract

BACKGROUND:

Patients with asthma uncontrolled on inhaled corticosteroids may benefit from umeclidinium (UMEC), a long-acting muscarinic antagonist.

METHODS:

This Phase IIb, double-blind study included patients with reversible, uncontrolled/partially-controlled asthma for ≥6 months, receiving ≥100 mcg/day fluticasone propionate (or equivalent) for ≥12 weeks. Following a 2-week run-in on open-label fluticasone furoate (FF) 100 mcg, patients were randomised (1:1:1) to receive UMEC 31.25 mcg, UMEC 62.5 mcg or placebo on top of FF 100 mcg once-daily for 24 weeks. As-needed salbutamol was provided. Primary and secondary endpoints were change from baseline in clinic trough forced expiratory volume in 1 s (FEV1) and clinic FEV1 3 h post-dose, respectively, at Week 24. Other endpoints included change from baseline in home daily spirometry (trough FEV1, evening FEV1, morning [pre-dose] and evening peak expiratory flow) over 24 weeks. Safety was assessed throughout the study.

RESULTS:

The intent-to-treat population comprised 421 patients (UMEC 31.25 mcg: n =139, UMEC 62.5 mcg: n =139, placebo: n =143). UMEC 31.25 mcg and 62.5 mcg demonstrated significantly greater improvements from baseline in clinic trough FEV1 at Week 24 (difference [95% CI]: 0.176 L [0.092, 0.260; p<0.001] and 0.184 L [0.101, 0.268; p<0.001], respectively), clinic FEV1 3 h post-dose at Week 24 (0.190 L [0.100, 0.279; p<0.001] and 0.198 L [0.109, 0.287; p<0.001], respectively) and mean change from baseline in daily home spirometry over 24 weeks versus placebo. No new safety signals were identified.

CONCLUSIONS:

UMEC is a highly effective bronchodilator that leads to improved lung function when administered as a single bronchodilator on top of FF in subjects with fully reversible, uncontrolled/partially-controlled moderate asthma. These data support a favourable benefit/risk profile for UMEC (31.25 mcg and 62.5 mcg).

TRIAL REGISTRATION:

GSK study ID: 205832; Clinicaltrials.gov ID: NCT03012061.

• Authors: Edward Kerwin, Steven Pascoe, Zelie Bailes, Robert Nathan, David Bernstein, Ronald Dahl, Robyn von Maltzahn, Kevin Robbins, Andrew Fowler, Laurie Lee
• Journal: Respiratory research (Respir Res) Vol. 21 Issue 1 Pg. 148 (Jun 12 2020) ISSN: 1465-993X [Electronic] England
• PMID: 32532275 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Bronchodilator Agents
• GSK573719
• Glucocorticoids
• Quinuclidines
• Fluticasone

Topics

• Administration, Inhalation
• Asthma (drug therapy, physiopathology)
• Bronchodilator Agents (administration & dosage)
• Double-Blind Method
• Drug Therapy, Combination
• Drug Tolerance
• Female
• Fluticasone (administration & dosage)
• Forced Expiratory Volume (drug effects)
• Glucocorticoids (administration & dosage)
• Humans
• Male
• Middle Aged
• Quinuclidines (administration & dosage)
• Treatment Outcome