Journal Article

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

Korn, Stephanie, Gessner, Christian, Foerster, Karin, Schuermann, Wolfgang, Sieder, Christian, Hiltl, Simone, Buhl, Roland

2015

Overview

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. Trial registration number NCT01120717.

• Publisher: BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adrenergic beta-2 Receptor Agonists - administration & dosage / Adrenergic beta-2 Receptor Agonists - adverse effects / Adrenergic beta-2 Receptor Agonists - therapeutic use / Aged / Antibiotics / Bronchodilator Agents - administration & dosage / Bronchodilator Agents - adverse effects / Bronchodilator Agents - therapeutic use / Chronic Obstructive Pulmonary Disease / Double-Blind Method / Drug Administration Schedule / Drug Combinations / Drug dosages / Dyspnea / Ethanolamines - administration & dosage / Ethanolamines - adverse effects / Ethanolamines - therapeutic use / Female / Forced Expiratory Volume - drug effects / Formoterol Fumarate / Glycopyrrolate - administration & dosage / Glycopyrrolate - adverse effects / Glycopyrrolate - analogs & derivatives / Glycopyrrolate - therapeutic use / Hospitalization / Humans / Indans - administration & dosage / Indans - adverse effects / Indans - therapeutic use / Inhalers / Male / Middle Aged / Patients / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - physiopathology / Quality of Life / Quinolones - administration & dosage / Quinolones - adverse effects / Quinolones - therapeutic use / Scopolamine Derivatives - administration & dosage / Scopolamine Derivatives - adverse effects / Scopolamine Derivatives - therapeutic use / Spirometry / Steroids / Tiotropium Bromide / Treatment Outcome / Vital Capacity - drug effects