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.

Trial registration number: NCT01120717.

Keywords: COPD Pharmacology.

Figure 1

Study design. b.i.d., twice daily; o.d., once daily; Pbo, placebo.

Figure 2

Patient disposition. FOR, formoterol; TIO, tiotropium.

Figure 3

SGRQ-C score at week 26, change from baseline in each treatment group (by FAS and PPS). The non-inferiority margin was –4 to 4 units (shown by dotted line). FAS, full analysis set; FOR, formoterol; PPS, per-protocol set; SGRQ-C, St George's Respiratory Questionnaire for patients with COPD; TIO, tiotropium.

Figure 4

SGRQ-C total score after 26 weeks. (A) LSM change from baseline in SGRQ-C total scores during treatment and (B) percentages of patients achieving the minimum clinically important difference (≥4 units) in SGRQ-C score after 26 weeks (FAS). FOR, formoterol; FAS, full analysis set; LSM, least squares mean; RR, risk ratio; SGRQ-C, St George's Respiratory Questionnaire in patients with COPD; TIO, tiotropium; ns, not significant.

Figure 5

TDI total score. (A) TDI total score (LSM) after 26 weeks and (B) percentages of patients achieving the minimum clinically important difference (≥1 units) (FAS). FOR, formoterol; FAS, full analysis set; LSM, least squares mean; RR, risk ratio; TDI, Transition Dyspnoea Index; TIO, tiotropium. ns, not significant. ^@p<0.05.

Figure 6

Lung function at week 12 and week 26 (FAS). (A) Pre-dose and post-dose FEV₁ and (B) pre-dose and post-dose FVC. FAS, full analysis set; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity. *p<0.001; ^#p<0.01; ns, not significant.