Onset of action of indacaterol in patients with COPD: Comparison with salbutamol and salmeterol-fluticasone

Beatrix Balint¹, Henrik Watz², Carolynn Amos³, Roger Owen³, Mark Higgins³, Benjamin Kramer⁴, On behalf of the INSURE* Study Investigators

¹Csongrád Megyei Önkormányzat Mellkasi Betegségek Szakkórháza, Deszk, Hungary; ²Pulmonary Research Institute, Hospital Grosshansdorf, Grosshansdorf, Germany; ³Novartis Horsham Research Centre, Horsham, West Sussex, UK; 4Novartis Pharmaceuticals, East Hanover, NJ, USA; *Indacaterol: starting quickly and remaining effective in COPD

Background: Indacaterol is a novel, inhaled once-daily ultra-long-acting ß₂-agonist for the treatment of chronic obstructive pulmonary disease (COPD).

Objectives: This study compared the onset of action of single doses of indacaterol 150 and 300 µg with salbutamol 200 µg, salmeterol-fluticasone 50/500 µg, and placebo in moderate-to-severe COPD patients.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled crossover study. The primary variable was forced expiratory volume in one second (FEV₁) at five minutes postdose.

Results: Out of 89 patients randomized (mean age 62 years), 86 completed the study. At five minutes postdose, both indacaterol doses were statistically and clinically superior to placebo (P < 0.001), with treatment–placebo differences in FEV₁ of 100 (95% confidence interval [CI] 70–130) mL and 120 (95% CI 90–150) mL for indacaterol 150 and 300 µg, respectively. FEV₁ at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol (10 and 30 mL for indacaterol 150 and 300 µg, respectively) and significantly higher than for salmeterol-fluticasone (50 mL, P = 0.003; 70 mL, P < 0.001, respectively). Moreover, both indacaterol doses showed significantly higher FEV₁ than placebo (P < 0.001) at all postdose time points. The numbers of patients with an FEV₁ increase of at least 12% and 200 mL at five minutes postdose were 16 (18.8%), 24 (27.6%), 20 (23.3%), 8 (9.1%), and 3 (3.4%) for indacaterol 150 and 300 µg, salbutamol 200 µg, salmeterol-fluticasone 50/500 µg, and placebo, respectively.

Conclusions: Single doses of indacaterol 150 and 300 µg demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol-fluticasone.

Keywords: indacaterol, onset of action, chronic obstructive pulmonary disease