Effect of once-daily indacaterol maleate/mometasone furoate on exacerbation risk in adolescent and adult asthma: a double-blind randomised controlled trial

Abstract

ObjectiveTo investigate the safety and efficacy of QMF149, a once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol maleate and inhaled corticosteroid (ICS) mometasone furoate (MF) for the treatment of persistent asthma. The hypothesis was that QMF149 would not increase the risk of serious asthma exacerbations.Setting174 research centres in nine countries.Participants1519 adolescents and adults with persistent asthma who were treated or qualified for treatment with combination LABA/ICS were randomised, and 1508 were included in the intention-to-treat analysis.InterventionPatients were randomised to QMF149 (indacaterol maleate 500 µg/MF 400 µg) or MF (400 µg) once daily via Twisthaler inhalation device in a double-blind, parallel-group study for 6–21 months.Primary and secondary outcome measuresThe primary end point was time to first serious asthma exacerbation (resulting in hospitalisation, intubation or death). The key secondary end point was annual rate of exacerbations requiring systemic corticosteroids.ResultsTreatment with QMF149 resulted in no significant difference in time to first serious exacerbation compared to MF (2 (0.3%) vs 6 events (0.8%); difference −0.52 percentage point; 95% CI −1.25 to 0.21, p=0.160, HR=0.31; 95% CI 0.06 to 1.54, p=0.151). QMF149 significantly reduced the annual rate of exacerbations requiring systemic corticosteroids (rate ratio=0.71; 95% CI 0.55 to 0.90, p=0.005). Proportions of patients experiencing adverse events were similar across groups (74.0% in the QMF149 group and 73.4% in the MF group). Serious adverse events occurred in 4% and 5.8% of patients in the QMF149 and MF groups, respectively.ConclusionsNo significant difference was observed in the primary outcome of time to first serious asthma exacerbation in patients treated with QMF149 compared with patients treated with MF. Long-term treatment with QMF149 once daily had a favourable safety/efficacy profile in adolescent and adult patients with persistent asthma.Trial registration numberClinicalTrials.gov; NCT00941798.

Lung Delivery of Indacaterol and Mometasone Furoate Following Inhalation of QMF149 in Healthy Volunteers

“…All reported AEs were mild in intensity, and no serious AE was reported. These safety findings are in agreement with those of a previous study conducted in patients with asthma …”

“…These safety findings are in agreement with those of a previous study conducted in patients with asthma. 12 This study assessed the contribution of lung and GI absorption to the total systemic exposure of indacaterol and mometasone furoate following oral inhalation of QMF149 via the TH device. The data from this study indicate that lung and GI absorption accounted for 25% and 75%, respectively, of the total systemic exposure of indacaterol.…”

The Debate About the Use of Long-Acting Inhaled ß-agonists in Asthma

“…Formoterol has a rapid onset of bronchodilation, and is approved for the acute relief of airflow obstruction in many countries, unlike salmeterol, whose onset to peak bronchodilation takes significantly longer than formoterol 16 . More recently, the benefit of ultra-long acting LABAs, such as vilanterol, have been demonstrated when added to an ICS in asthma 11,17 , and this combination has been approved for use in many countries, while others are still under clinical development for use in asthma 12,18 .…”

The Statement of the Polish Society of Allergology Experts on the Treatment of Difficult-To-Treat Asthma

“…Indacaterol is an uLABA registered for use in treatment of patients with COPD in the USA and Europe. The results of a randomised, double-blind clinical trial demonstrated that indacaterol in combination with mometasone furoate was at least as efficacious as mometasone with respect to the time to the first serious asthma exacerbation (0.3% vs. 0.8%; p = 0.16) [28]. A combination of indacaterol and mometasone was superior to mometasone www.pneumonologia.viamedica.pl alone with respect to the total number of asthma exacerbations requiring oral glucocorticosteroids per year (rate ratio: 0.71; 95% CI: 0.55 to 0.90; p = 0.005).…”