title: Pooled safety analysis of the fixed-dose combination of indacaterol and glycopyrronium (QVA149), its monocomponents, and tiotropium versus placebo in COPD patients.
abstract: BACKGROUND
  To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases.
  
  
  METHODS
  Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of ≥3 month's duration with at least two of the treatment groups: QVA149 110/50 μg, glycopyrronium 50 μg, indacaterol 150 μg, placebo or tiotropium 18 μg. Overall hazard ratio (HR) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction, inhaled corticosteroid use, cardiovascular risk factors, sex, age and body mass index for death, serious cases of cardio- and cerebrovascular (CCV) events, major adverse cardiovascular events (MACEs), pneumonia, COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation (AF/F).
  
  
  RESULTS
  The HR for QVA149 versus placebo showed no significant increase in the overall risk for death (HR [95% confidence interval]: 0.93 [0.34-2.54]); CCV events (0.60 [0.29-1.24]); MACE (1.04 [0.45-2.42]); pneumonia (1.10 [0.54-2.25]); COPD exacerbations (0.60 [0.40-0.91]); and AF/F (1.03 [0.49-2.18]). Similar results were observed for indacaterol, glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups.
  
  
  CONCLUSIONS
  There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149, and it had a comparable safety profile as its monocomponents and tiotropium versus placebo.
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: j.wedzicha@imperial.ac.uk.
authors.forename: Jadwiga A
authors.initials: JA
authors.lastname: Wedzicha
authors.affiliation: Allergy Department, Odense University Hospital, Odense, Denmark.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Pulmonary Department, Mainz University Hospital, Mainz, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Buhl
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Agnes
authors.initials: A
authors.lastname: Schubert-Tennigkeit
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Hungta
authors.initials: H
authors.lastname: Chen
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: D'Andrea
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Fogel
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Banerji
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; 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; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000627:therapeutic use*; D012307:Risk Factors; D012602:Scopolamine Derivatives / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C554862:indacaterol-glycopyrronium combination; C510790:indacaterol; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: Glycopyrronium; Indacaterol; Pooled analysis; QVA149; Safety; Tiotropium