FLIGHT1 and FLIGHT2: Efficacy and Safety of QVA149 (Indacaterol/Glycopyrrolate) versus Its Monocomponents and Placebo in Patients with Chronic Obstructive Pulmonary Disease

摘要

Rationale: Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy recommends the combination of two long-acting bronchodilators of different pharmacologic classes for the management of chronic obstructive pulmonary disease (COPD) if symptoms are not adequately controlled by a single bronchodilator. Objectives: The FLIGHT1 and FLIGHT2 studies evaluated the efficacy and safety of QVA149 (indacaterol/glycopyrrolate), a fixed-dose combination of a long-acting β_2-agonist (indacaterol) and a long-acting muscarinic antagonist (glycopyrrolate), compared with its monocomponents and placebo in patients with moderate-to-severe COPD. Methods: FLIGHT1 and FLIGHT2 were 12-week, identical, multicenter, randomized, double-blind, parallel-group, placebo-and active-controlled studies. Patients were randomized (1:1:1:1) to indacaterol/glycopyrrolate (27.5/15.6 μg twice daily), indacaterol (27.5 μg twice daily), glycopyrrolate (15.6 μg twice daily), or placebo, all delivered via the Neohaler device. The primary objective was to demonstrate the superiority of indacaterol/glycopyrrolate versus its monocomponents for standardized area under the curve from 0-12 hours for FEV_1 at Week 12. Secondary objectives included St. George's Respiratory Questionnaire total score and transition dyspnea index total score and reduction in daily rescue medication use with indacaterol/glycopyrrolate versus placebo. Measurements and Main Results: In total, 2,038 patients were included in the pooled analysis. Indacaterol/glycopyrrolate was statistically superior in terms of FEV_1 area under the curve from 0-12 hours compared with its monocomponents (P ＜ 0.001). Statistically and clinically meaningful improvements in St. George's Respiratory Questionnaire total score, transition dyspnea index total score, and reduction in rescue medication use were observed with indacaterol/ glycopyrrolate compared with placebo (P ＜ 0.001). The safety profile was comparable across the treatment groups. Conclusions: Indacaterol/glycopyrrolate twice daily can be an alternative treatment option for the management of symptomatic patients with moderate-to-severe COPD.