Indacaterol acetate/mometasone furoate provides sustained improvements in lung function compared with salmeterol xinafoate/fluticasone propionate in patients with moderate-to-very-severe COPD: results from a Phase II randomized, double-blind 12-week study

Abstract

Background and purposeFixed-dose combinations of a long-acting beta agonist and an inhaled corticosteroid are more effective than the individual components in COPD. The primary study objective was to demonstrate that the combination indacaterol acetate/mometasone furoate (IND/MF [QMF149]) was non-inferior to the twice-daily combination salmeterol xinafoate/fluticasone propionate (Sal/Flu) in terms of trough FEV1 at week 12 (day 85). Secondary objectives were to compare the efficacy of IND/MF (QMF149) vs Sal/Flu with respect to other lung function parameters, COPD exacerbations, symptoms and dyspnea, health status/health-related quality of life, and rescue medication use.Materials and methodsThis was a 12-week multicenter, randomized, double-blind, double-dummy, parallel-group, Phase II study in patients with moderate-to-very-severe COPD, who were randomized (1:1) to IND/MF (QMF149) (150/160 µg once daily; n=316) or Sal/Flu (50/500 µg twice daily; n=313).ResultsOver 90% of patients completed the study: 94.6% in the IND/MF (QMF149) group and 92.0% in the Sal/Flu group. The primary objective of non-inferiority of IND/MF (QMF149) to Sal/Flu for trough FEV1 at week 12 (day 85) was met: the lower limit of the CI (95% CI: 27.7, 83.3 mL) was greater than −60 mL. The analysis for superiority of IND/MF (QMF149) to Sal/Flu demonstrated superiority of IND/MF (QMF149), with a difference of 56 mL (P<0.001). In addition, IND/MF (QMF149) treatment significantly improved COPD exacerbation-related parameters during the 12-week period. Other significant improvements with IND/MF (QMF 149) vs Sal/Flu were noted for dyspnea at week 12 and other COPD symptoms and COPD rescue medication use over the 12 weeks. The safety and tolerability profiles of both the treatments were similar.ConclusionIND/MF (QMF149) (150/160 µg once daily) offered superior lung function and symptom efficacy and a favorable safety profile compared with Sal/Flu (50/500 µg twice daily) in patients with moderate-to-very severe COPD.

Formulation of Dry Powders for Inhalation Comprising High Doses of a Poorly Soluble Hydrophobic Drug

“…Indeed, an increase in post-inhalation cough was observed for inhaled indacaterol maleate where disproportionation is favored (Donohue et al, 2011;Beasley et al, 2015). This was mitigated by using a weaker acid to form the salt (acetic acid) or by formation of a co-crystal (Beasley et al, 2015;Beeh et al, 2018). For the suspension-based PulmoSphere formulation of GDC-A, the drug is maintained as the free base.…”

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

“…The impact of salt disproportionation may be mitigated by using a neutral form of the drug, through the use of a cocrystal or by forming salts from acids with higher pK a values [ 12 ]. This was demonstrated with inhaled bronchodilator, indacaterol, where a switch from the maleate salt (pK a = 1.85) to the acetate salt (pK a = 4.75) significantly reduced the incidence of post-inhalation cough [ 12 , 145 , 146 ].…”

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

“…The impact of salt disproportionation may be mitigated by using a neutral form of the drug, through the use of a co-crystal, or by forming salts from acids with higher pKa values [12]. This was demonstrated with the inhaled bronchodilator, indacaterol, where a switch from the maleate salt (pKa = 1.85) to the acetate salt (pKa = 4.75) significantly reduced the incidence of post-inhalation cough [12,[146][147].…”