Elsevier

Respiratory Medicine

Volume 109, Issue 1, January 2015, Pages 54-62
Respiratory Medicine

The effect of fluticasone furoate/umeclidinium in adult patients with asthma: A randomized, dose-ranging study

https://doi.org/10.1016/j.rmed.2014.09.012Get rights and content
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Summary

Background

We evaluated the dose–response of umeclidinium (UMEC; a long-acting muscarinic antagonist) combined with fluticasone furoate (FF; an inhaled corticosteroid [ICS]) in patients with asthma.

Methods

In a double-blind, three-period crossover study, 421 subjects (symptomatic on ICS), were randomized to a sequence of three of seven treatments: FF 100 mcg alone, FF 100 mcg combined with UMEC (15.6, 31.25, 62.5, 125, or 250 mcg), or vilanterol 25 mcg (a long-acting β-agonist), inhaled once-daily for 14 days (12–14-day washout). Trough forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and safety were assessed.

Results

Period baseline was a significant covariate, indicating a potential carryover effect between treatment periods. Across all treatment periods, trough FEV1 improved with FF/UMEC 125 and 250 versus FF (treatment difference 0.055 L [both doses]; p = 0.018). FF/UMEC increased morning (15.9–22.9 L/min) and evening (16.2–28.8 L/min) PEF versus FF. As intended assessments were confounded, post hoc Period 1 data analyses were performed, demonstrating significant increases in trough FEV1 with FF/UMEC 31.25, 62.5, and 250 versus FF. Trough FEV1 improvements with FF/UMEC were greater in subjects with fixed (0.095–0.304 L) versus non-fixed (−0.084 to 0.041 L) obstruction. The incidence of on-treatment adverse events was 13–25% across groups. No treatment-related effects on laboratory parameters were reported.

Conclusion

FF/UMEC may be a viable treatment for patients with asthma symptomatic on ICS; benefit may be most prominent in those with fixed obstruction. The carryover effect suggests future UMEC studies should use an alternative design.

ClinicalTrials.gov: NCT01573624.

Keywords

Asthma
Fixed-dose combination
Muscarinic antagonist
Inhaled corticosteroid
Trough FEV1

Abbreviations

AE
adverse event
CI
confidence interval
COPD
chronic obstructive pulmonary disease
DPI
dry powder inhaler
ECG
electrocardiogram
FEV1
forced expiratory volume in one second
FF
fluticasone furoate
FVC
forced vital capacity
GCP
Good Clinical Practice
ICS
inhaled corticosteroid
ICH
International Conference on Harmonisation
ITT
intent-to-treat
LABA
long-acting β-agonist
LAMA
long-acting muscarinic antagonist
LS
least squares
MedDRA
Medical Dictionary for Regulatory Activities
PEF
peak expiratory flow
SAE
serious adverse event
SD
standard deviation
SE
standard error
UMEC
umeclidinium bromide
VI
vilanterol

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