Efficacy And Safety Of Indacaterol/Glycopyrronium/Mometasone Furoate Versus Salmeterol/Fluticasone Plus Tiotropium In Uncontrolled Asthma: The ARGON Study

Aim: A once-daily (o.d.) fixed-dose combination of indacaterol (IND, long-acting β2-agonist [LABA]), glycopyrronium (GLY, long-acting muscarinic antagonist) and mometasone furoate (MF, inhaled corticosteroid [ICS]) is under development for maintenance treatment in asthma. This study evaluated efficacy and safety of IND/GLY/MF vs concurrent administration with salmeterol/fluticasone (Sal/Flu)+tiotropium (Tio) in patients with uncontrolled asthma (NCT0318311).Methods: This Phase IIIb,24-week, multicentre, 3-arm, parallel-group, partially blinded (for IND/GLY/MF doses), active treatment controlled (open-label), non-inferiority study randomised (1:1:1) patients (≥18 years) symptomatic (Asthma Control Questionnaire [ACQ-7] ≥1.5) prior to randomisation; with history of ≥1 severe asthma exacerbation during the previous year, despite LABA/ICS (medium- or high-dose) treatment to IND/GLY/MF medium- (150/50/80 μg) or high-dose (150/50/160 μg) o.d. via Breezhaler® or concurrent administration with Sal/Flu high-dose (50/500 μg) twice-daily (b.i.d.) via Diskus® + Tio 5 μg o.d. via Respimat®. The primary objective: non-inferiority (margin of −0.25) of IND/GLY/MF medium- or high-dose vs Sal/Flu+Tio in the change from baseline (CFB) in Asthma Quality of Life Questionnaire (AQLQ) total score at Week 24. The secondary endpoints: CFB in trough forced expiratory volume in 1 second (FEV1) at Week 24 and CFB in ACQ-7 total score over 24-weeks of treatment. Safety was also assessed.Results: In total, 1426 patients were randomised to IND/GLY/MF medium- or high-dose or Sal/Flu+Tio. IND/GLY/MF medium- and high-dose met the primary endpoint i.e., both doses showed non-inferiority when compared with Sal/Flu+Tio (least square mean treatment difference [LSMTD]: −0.038 and 0.073, respectively; one-sided non-inferiority p<0.001 for both comparisons) (Figure 1A) in terms of AQLQ. IND/GLY/MF high-dose showed greater improvements in trough FEV1 (LSMTD: 96 mL; p<0.001; Figure 1B) and asthma control (ACQ-7; LSMTD: −0.124; p=0.004) vs Sal/Flu+Tio. Improvements with IND/GLY/MF medium-dose in trough FEV1 (Figure 1B) and asthma control (LSMTD: −0.032; p=0.245) were comparable with Sal/Flu+Tio. Both IND/GLY/MF doses had a favourable safety profile and comparable with Sal/Flu+Tio.Conclusions: Two doses of IND/GLY/MF fixed-dose combination, single inhaler once-daily showed either comparable or better efficacy vs twice-daily Sal/Flu+ once-daily Tio (concurrent administration two inhalers). Both once-daily IND/GLY/MF doses showed non-inferiority with respect to improvements in quality of life vs twice-daily Sal/Flu high-dose + once-daily Tio. Once-daily IND/GLY/MF high-dose showed greater improvements in lung function and asthma control vs twice-daily Sal/Flu high-dose + once-daily Tio. Once-daily IND/GLY/MF medium-dose showed comparable improvements in lung function and asthma control vs twice-daily Sal/Flu high-dose + once-daily Tio with a reduced steroid exposure. Implementation Science/Service Development Research Ideas on Respiratory Conditions and Tobacco Dependency Abstract Declaration of Interest The study was funded by Novartis Pharma AG. References and Clinical Trial Registry Information Clinicaltrials.gov:NCT0318311