Efficacy and Safety of Indacaterol/Glycopyrronium/Mometasone Furoate in Patients with Uncontrolled Asthma: The Phase III IRIDIUM Study

Aim:The IRIDIUM study (NCT02571777) assessed the efficacy and safety of indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF), a once-daily (o.d.) fixed-dose combination of a long-acting β2-agonist/long-acting muscarinic antagonist/inhaled corticosteroid (LABA/LAMA/ICS), versus LABA/ICS in patients with uncontrolled asthma.Methods:IRIDIUM was a Phase III, multicentre, 52-week, randomised, double-blind, double-dummy, parallel-group, active-control study that included patients (≥18–≤75 years) who were symptomatic (Asthma Control Questionnaire [ACQ-7] ≥1.5) at screening, had ≥1 severe exacerbation in previous year and forced expiratory volume in 1 second (FEV1) <80%. Patients were randomised (1:1:1:1:1) to receive IND/GLY/MF medium-dose (150/50/80 μg), IND/GLY/MF high-dose (150/50/160 μg), or IND/MF medium-dose (150/160 µg), IND/MF high-dose (150/320 µg) o.d., all via Breezhaler®, or salmeterol/fluticasone high-dose (Sal/Flu; 50/500 µg) twice-daily (b.i.d.), via Diskus®. Primary endpoint was superiority in trough FEV1 with IND/GLY/MF versus IND/MF at Week 26. Key secondary endpoint was improvement in ACQ-7 score after 26 weeks; other secondary endpoint was reduction in annualised rate of asthma exacerbations over 52 weeks.Results:In total, 3092 patients were randomised. At Week 26, the primary endpoint was met with both IND/GLY/MF medium- and high-dose demonstrating superiority in improvement in trough FEV1 versus the respective IND/MF doses (both p<0.001; Figure 1). Both IND/GLY/MF medium- and high-dose also demonstrated significant improvement in trough FEV1 versus Sal/Flu (p<0.001). These improvements were sustained through Week 52. Clinically meaningful improvements in ACQ-7 score from baseline were observed across all treatment arms (IND/GLY/MF medium-dose: −0.97; IND/GLY/MF high-dose: −0.99; IND/MF medium-dose: −0.90; IND/MF high-dose: −0.99; Sal/Flu: −0.89). The difference between doses of IND/GLY/MF and the respective IND/MF doses at Week 26 for ACQ-7 score however did not achieve statistical significance. IND/GLY/MF medium-dose reduced annualised rates of moderate/severe and severe asthma exacerbations by 13% (95% CI, 0.71–1.06; non-significant [ns]) and 7% (95% CI, 0.74–1.17; ns), respectively, versus IND/MF medium-dose. IND/GLY/MF high-dose reduced annualised rates of moderate/severe and severe asthma exacerbations by 15% (95% CI, 0.68–1.04; ns) and 22% (95% CI, 0.61–1.00; ns), respectively, versus IND/MF high-dose, and by 36% (95% CI, 0.52–0.78; p<0.001) and 42% (95% CI, 0.45–0.73; p<0.001), respectively, versus Sal/Flu. Safety was comparable across treatment arms and no new safety signals were observed.Conclusions:The combination inhaled therapy of once-daily IND/GLY/MF medium-dose and high-dose significantly improved lung function versus the comparators, demonstrated comparable improvements in asthma control from baseline versus the respective once-daily IND/MF doses and twice-daily Sal/Flu high-dose, and reduced asthma exacerbations versus this standard-of-care in patients with uncontrolled asthma. Implementation Science/Service Development Research Ideas on Respiratory Conditions and Tobacco Dependency Abstract Declaration of Interest Study funded by Novartis Pharma AG. References and Clinical Trial Registry Information Clinicaltrials.gov:NCT02571777