Bronchodilator efficacy and safety of indacaterol 150 μg once daily in patients with COPD: an analysis of pooled data

Abstract

Background: Indacaterol is an inhaled, once-daily long-acting β(2)-agonist bronchodilator for regular use in patients with chronic obstructive pulmonary disease (COPD). As indacaterol is the first once-daily β(2)-agonist to be developed, it is relevant to evaluate its bronchodilator efficacy, safety, and tolerability.

Methods: Data were pooled from three randomized, double-blind, clinical studies in patients with moderate-to-severe COPD treated with indacaterol 150 μg qd (n = 627) or placebo (n = 1021). Bronchodilator efficacy was assessed as trough (24-hour post-dose) forced expiratory volume in 1 second (FEV(1)) after 12 weeks (primary endpoint in individual studies) and FEV(1) measured serially post-dose. Rescue use of albuterol was monitored.

Results: At week 12, indacaterol increased trough FEV(1) by 160 mL compared with placebo (P < 0.001), exceeding the 120 mL level prespecified as clinically important. FEV(1) during the first 12-hour post-dose at week 12 averaged 210 mL higher with indacaterol than with placebo (P < 0.001). Patients receiving indacaterol recorded 53% of days without use of rescue albuterol, compared with 38% of days in the placebo group (P < 0.001). Adverse events (mostly mild or moderate) were reported for 52% and 46% of patients receiving indacaterol and placebo, respectively, and serious adverse events for 4% and 5%. Worsening of COPD was the most frequent adverse event (10% indacaterol; 15% placebo). Indacaterol had little effect on pulse or blood pressure or measures of systemic β(2)-adrenoceptor activity (blood glucose, serum potassium, and corrected QT interval).

Conclusion: Indacaterol was an effective bronchodilator and was well tolerated, with a good safety profile over 12 weeks of treatment. It should prove a useful treatment for patients with moderate-to-severe COPD.

Trial registration: ClinicalTrials.gov NCT00393458 NCT00624286.

Keywords: chronic obstructive pulmonary disease; inhaled corticosteroids; tolerability.

Figure 1

Trough forced expiratory volume in 1 second: differences between indacaterol and placebo treatment after first dose (measured on day 2) and after 12 weeks’ treatment. Broken line indicates prespecified level of clinical importance. Notes: Data are least squares means and 95% confidence intervals. ***Denotes P < 0.001 vs placebo.

Figure 2

Trough FEV₁ after the first dose (day 2) and after 12 weeks of treatment, expressed as change from baseline (absolute (A) and percentage (B)). Note: Data are unadjusted means ± standard error. Abbreviation: FEV₁, forced expiratory volume in 1 second.

Figure 3

FEV₁ measured at serial time points post-dose on day 1 and week 12. Note: Data are unadjusted means (error bars omitted for clarity). Abbreviation: FEV₁, forced expiratory volume in 1 second.

Figure 4

FEV₁ measured at serial time points up to 60 minutes post-dose on day 1. Notes: Data are least squares means ± standard error. ***Denotes P < 0.001 vs placebo. Abbreviation: FEV1, forced expiratory volume in 1 second.

Figure 5

FVC measured at serial time points post-dose after 12 weeks in a single study. Notes: Data are least squares means ± standard error. Differences between indacaterol and placebo were statistically significant (P < 0.001) at each time point. Abbreviation: FVC, forced vital capacity.

Figure 6

Percentage of days with no use of rescue albuterol over 3 months of treatment. Notes: Data are least squares means ± standard error. ***Denotes P < 0.001 vs placebo.