Indacaterol is a novel once-daily (qd) inhaled long-acting β2-agonist. This double-blind, randomized study investigated efficacy and safety of indacaterol in COPD patients versus placebo and salmeterol.
Moderate-severe COPD patients received indacaterol 150 μg qd, salmeterol 50 μg twice-daily, or placebo for 26 weeks. Efficacy assessments included 24-h post-dose (trough) FEV1 after 12 weeks (primary endpoint), health status (St George s Respiratory Questionnaire, SGRQ), transition dyspnea index (TDI), and days without use of rescue albuterol.
998 patients (age 63.5 years, post-albuterol FEV1 53.4% predicted, FEV1/FVC 0.53) were treated; 84% completed. Trough FEV1 after 12 weeks with indacaterol was 170 mL higher than placebo (p<0.001), exceeding the prespecified 120 mL level of clinical significance, and 60 mL higher than salmeterol (p<0.001). These significant treatment differences (p<0.001) were maintained at Week 26. Indacaterol-treated patients reported improved health status, with a clinically important difference of 6.3 units versus placebo in SGRQ total score (p<0.001), and a 2.1-unit difference over salmeterol (p<0.05), at Week 12. A clinically important difference over placebo was maintained at 26 weeks (5 units; p<0.001). Indacaterol improved the Week 12 TDI total score by a clinically meaningful difference of 1.45 over placebo (p<0.001) and by 0.55 over salmeterol (p=0.015), and allowed significantly more rescue-free days over 26 weeks (60% with indacaterol vs 42% with placebo [p<0.001] and 55% with salmeterol [p<0.05]). The incidence of adverse events for indacaterol, salmeterol, and placebo, respectively, was 51%, 46% and 47%. Most common were COPD worsening (18%, 15%, 19%) and nasopharyngitis (7%, 9%, 6%). Five deaths were reported (one indacaterol, one salmeterol, three placebo), none suspected related to study treatment.
Once-daily indacaterol 150 μg was superior to twice-daily salmeterol in its 24-h bronchodilator effect, provided better health status and improved other clinical outcomes more than salmeterol. The incidence of adverse events was similar to placebo.
The effective bronchodilation and improved clinical outcomes predict indacaterol will be a useful maintenance treatment for patients with moderate-severe COPD.
Employee: RO, AL, CL and BK are Novartis employees. Consultant fee, speaker bureau, advisory committee, etc: OK has presented at symposia sponsored by Astra Zeneca, Boehringer, GlaxoSmithKline, Novartis, Pfizer, and received fees for consulting from Altana, Boehringer, Novartis.