title: Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study.
abstract: BACKGROUND
  QVA149 is a once-daily (o.d.) inhaled dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium for the treatment of COPD. The QUANTIFY study compared QVA149 with a free-dose bronchodilator combination of tiotropium plus formoterol (TIO+FOR) in improving health-related quality of life (HRQoL) of patients with COPD.
  
  
  METHODS
  This multicentre, blinded, triple-dummy, parallel-group, non-inferiority study randomised patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s (FEV1) ≥30% to <80% predicted) to QVA149 110/50 µg o.d. or TIO 18 µg o.d.+ FOR 12 µg twice daily (1:1) for 26 weeks. The primary endpoint was to demonstrate non-inferiority in HRQoL assessed using St George's Respiratory Questionnaire-COPD (SGRQ-C). The prespecified non-inferiority margin was 4 units. Secondary endpoints included Transition Dyspnoea Index (TDI) score, pre-dose FEV1, forced vital capacity (FVC) and safety.
  
  
  RESULTS
  Of the 934 patients randomised (QVA149=476 and TIO+FOR=458), 87.9% completed the study. At week 26, non-inferiority was met for SGRQ-C (QVA149 vs TIO+FOR; difference: -0.69 units; 95% CI -2.31 to 0.92; p=0.399). A significantly higher percentage of patients achieved a clinically relevant ≥1 point improvement in TDI total score with QVA149 (49.6%) versus TIO+FOR (42.4%; p=0.033). QVA149 significantly increased pre-dose FEV1 (+68 mL, 95% CI 37 mL to 100 mL; p<0.001) and FVC (+74 mL, 95% CI 24 mL to 125 mL; p=0.004) compared with TIO+FOR at week 26. The incidence of adverse events was comparable between both treatments (QVA149=43.7% and TIO+FOR=42.6%).
  
  
  CONCLUSIONS
  QVA149 is non-inferior to TIO+FOR in improving HRQoL, with clinically meaningful and significant improvements in breathlessness and lung function in patients with COPD.
  
  
  BACKGROUND
  NCT01120717.
authors: III.Medizinische Klinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz K.d.ö.R., Mainz, Germany.
authors: Roland
authors: R
authors: Buhl
authors: Universitätsklinikum Leipzig, Leipzig, Germany POIS Leipzig GbR, Leipzig, Germany.
authors: Christian
authors: C
authors: Gessner
authors: Pneumologische Praxis, Marburg, Germany.
authors: Wolfgang
authors: W
authors: Schuermann
authors: Kardio-Pneumologische Praxis, Berlin, Germany.
authors: Karin
authors: K
authors: Foerster
authors: Novartis Pharma GmbH, Nürnberg, Germany.
authors: Christian
authors: C
authors: Sieder
authors: Novartis Pharma GmbH, Nürnberg, Germany.
authors: Simone
authors: S
authors: Hiltl
authors: Universitätsmedizin der Johannes Gutenberg-Universität, Mainz, Germany.
authors: Stephanie
authors: S
authors: Korn
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006024:Glycopyrrolate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012602:Scopolamine Derivatives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069447:Tiotropium Bromide; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D007189:Indans; D015363:Quinolones; D012602:Scopolamine Derivatives; C554862:indacaterol-glycopyrronium combination; D006024:Glycopyrrolate; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
keywords: COPD Pharmacology