ONCE-DAILY INDACATEROL PROVIDES SUPERIOR BRONCHODILATION, HEALTH STATUS AND CLINICAL OUTCOMES COMPARED WITH SALMETEROL IN PATIENTS WITH CHRONIC OBSTRUCTIVE COPD: A 26-WEEK PLACEBO-CONTROLLED STUDY

Abstract

PURPOSE: 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. METHODS: Moderate-severe COPD patients received indacaterol 150 μg qd, salmeterol 50 μg twicedaily, 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. RESULTS: 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. CONCLUSION: 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. CLINICAL IMPLICATIONS: The effective bronchodilation and improved clinical outcomes predict indacaterol will be a useful maintenance treatment for patients with moderate-severe COPD.