title: FLIGHT1 and FLIGHT2: Efficacy and Safety of QVA149 (Indacaterol/Glycopyrrolate) versus Its Monocomponents and Placebo in Patients with Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The FLIGHT1 and FLIGHT2 studies evaluated the efficacy and safety of QVA149 (indacaterol/glycopyrrolate), a fixed-dose combination of a long-acting β2-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 FEV1 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.
  
  
  RESULTS
  In total, 2,038 patients were included in the pooled analysis. Indacaterol/glycopyrrolate was statistically superior in terms of FEV1 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. Clinical trial registered with www.clinicaltrials.gov (NCT 01727141 and NCT 0171251).
authors.affiliation: 1 Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.|2 Valley Regional Hospital, Claremont, New Hampshire.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Mahler
authors.affiliation: 3 Clinical Research Institute of Southern Oregon, Medford, Oregon.
authors.forename: Edward
authors.initials: E
authors.lastname: Kerwin
authors.affiliation: 4 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Tim
authors.initials: T
authors.lastname: Ayers
authors.affiliation: 4 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Angel
authors.initials: A
authors.lastname: FowlerTaylor
authors.affiliation: 5 Novartis Healthcare Pvt. Ltd., Hyderabad, India; and.
authors.forename: Samopriyo
authors.initials: S
authors.lastname: Maitra
authors.affiliation: 4 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Chau
authors.initials: C
authors.lastname: Thach
authors.affiliation: 4 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Mark
authors.initials: M
authors.lastname: Lloyd
authors.affiliation: 6 Novartis Pharma AG, Basel, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patalano
authors.affiliation: 4 Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D001993:Bronchodilator Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006024:Glycopyrrolate / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000627:therapeutic use*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D018727:Muscarinic Antagonists; D015363:Quinolones; C554862:indacaterol-glycopyrronium combination; C510790:indacaterol; D006024:Glycopyrrolate
keywords: COPD; clinical trial; fixed-dose combination; long-acting muscarinic antagonist; long-acting β2-agonists