Nicola Gallagher

Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study

We investigated the efficacy and safety of dual bronchodilation with QVA149 versus its monocomponents indacaterol and glycopyrronium, tiotropium and placebo in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). This was a multicentre, randomised, double-blind, placebo- and active-controlled, 26-week trial. Patients (n = 2144) were randomised (2:2:2:2:1) to receive once-daily QVA149 (indacaterol 110 &mgr;g/glycopyrronium 50 &mgr;g), indacaterol 150 &mgr;g, glycopyrronium 50 &mgr;g, open-label tiotropium 18 &mgr;g or placebo. The primary end-point was trough forced expiratory volume in 1 s (FEV1) at week 26 for QVA149 versus its monocomponents. Secondary end-points included dyspnoea, health status, rescue medication use and safety. Trough FEV1 at week 26 was significantly improved (p<0.001) with QVA149 compared with indacaterol and glycopyrronium (least squares mean (LSM) differences 0.07 L and 0.09 L, respectively), tiotropium and placebo (LSM differences 0.08 L and 0.20 L, respectively); these beneficial effects were sustained throughout the 26-week study. QVA149 significantly improved dyspnoea and health status versus placebo (p<0.001 and p = 0.002, respectively) and tiotropium (p = 0.007 and p = 0.009, respectively) at week 26. All treatments were well tolerated. Dual bronchodilation with once-daily QVA149 demonstrated superior and clinically meaningful outcomes versus placebo and superiority versus treatment with a single bronchodilator, with a safety and tolerability profile similar to placebo, supporting the concept of fixed-dose long-acting muscarinic antagonist/long-acting &bgr;2-agonist combinations for the treatment of COPD. Dual indacaterol/glycopyrronium therapy was safe and more efficacious than monotherapy in moderate-to-severe COPD http://ow.ly/p3H5E

Efficacy and safety of NVA237 versus placebo and tiotropium in patients with COPD: the GLOW2 study

NVA237 (glycopyrronium bromide) is a once-daily long-acting muscarinic antagonist (LAMA) in development for chronic obstructive pulmonary disease (COPD). The GLycopyrronium bromide in COPD airWays clinical Study 2 (GLOW2) evaluated the efficacy and safety of NVA237 in moderate-to-severe COPD over 52 weeks. Patients were randomised 2:1:1 to NVA237 50 μg, placebo or open-label tiotropium 18 μg for 52 weeks. Primary end-point was trough forced expiratory volume in 1 s (FEV1) at 12 weeks. 1,066 patients were randomised, 810 completed the study. At week 12, trough FEV1 increased significantly by 97 mL with NVA237 (95% CI 64.6–130.2; p<0.001) and 83 mL with tiotropium (95% CI 45.6–121.4; p<0.001). Compared with placebo, NVA237 produced significant improvements in dyspnoea (Transition Dyspnoea Index at week 26; p=0.002) and health status (St Georges Respiratory Questionnaire at week 52; p<0.001). NVA237 significantly reduced the risk of moderate-to-severe COPD exacerbations by 34% (p=0.001) and the use of rescue medication (p=0.039), versus placebo. NVA237-placebo and tiotropium-placebo differences were comparable for all outcomes. Safety profiles were similar across groups. NVA237 50 μg provided significant improvements in lung function, dyspnoea, health status, exacerbations and rescue medication use, versus placebo, and was comparable to tiotropium. NVA237 can potentially be an alternative choice of LAMA for COPD patients.

Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study

We evaluated the effect of QVA149, a dual bronchodilator combining indacaterol and glycopyrronium, on direct patient-reported dyspnoea in patients with moderate-to-severe chronic obstructive pulmonary disease. In this multicentre, blinded, double-dummy, three-period crossover study, 247 patients were randomised to once-daily QVA149 110/50 μg, placebo or tiotropium 18 μg. Superiority of QVA149 versus placebo (primary objective) and tiotropium (secondary objective) was assessed for improvement in dyspnoea via the self-administered computerised (SAC) version of the Baseline and Transition Dyspnoea Index after 6 weeks. Secondary end-points included lung function, rescue medication use and safety. After 6 weeks, the SAC Transition Dyspnoea Index total score was significantly higher with QVA149 versus placebo (least squares mean (LSM) treatment difference 1.37, p<0.001) and tiotropium (LSM treatment difference 0.49, p=0.021). QVA149 provided significant improvements in lung function, with higher forced expiratory volume in 1 s area under the curve from 0–4 h post-dose versus placebo and tiotropium at day 1 and week 6 (all p<0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p<0.001) and tiotropium (p=0.002). All treatments were well tolerated. Once-daily QVA149 provided superior improvements in patient-reported dyspnoea and lung function versus placebo and tiotropium. These benefits were associated with improvements in other symptoms and reduced use of rescue medication. Two different bronchodilators in a single inhaler were effective in relieving patient-reported dyspnoea in COPD http://ow.ly/qjIpe

P236 Superior lung function with once-daily QVA149 translates into improvements in patient-reported breathlessness compared with placebo and tiotropium in COPD patients: the BLAZE study

Introduction QVA149, a novel once-daily inhaled dual bronchodilator combining a fixed dose of the long-acting β2 agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium, has demonstrated improvements in dyspnoea versus its mono-components (indacaterol and glycopyrronium), tiotropium, and salmeterol/fluticasone using the interviewer-based Transition Dyspnoea Index (TDI) questionnaire.1,2 The BLAZE study evaluated the effect of once-daily QVA149 on patient-reported dyspnoea versus placebo and blinded tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods This was a 6 week, multicentre, randomised, blinded, double-dummy, placebo-controlled, 3-period, cross-over study. Patients aged ≥40 years with moderate-to-severe COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <80% of the predicted normal, and post-bronchodilator FEV1/ forced vital capacity <0.7 were randomised to receive QVA149 110/50 μg (via the Breezhaler® device) or placebo (via the Breezhaler®/ HandiHaler® device) or blinded tiotropium 18 μg (via the HandiHaler® device). The primary objective of the study was to evaluate the superiority of QVA149 versus placebo in the improvement of patient-reported dyspnoea as assessed by Self-Administered Computerised (SAC) version of the Baseline Dyspnoea Index (BDI)/TDI after 6 weeks of treatment. Other objectives included; standardised FEV1 area under the curve from 0 to 4 hours post-dose (AUC0–4 h); rescue medication use; safety and tolerability. Abstract P236 Figure 1. TDI total score after 6 Weeks. Results Of the 247 patients (mean age 62.8 years) randomised, 191 completed the study. The SAC TDI total score was significantly improved with QVA149 compared with placebo and tiotropium after 6 weeks (figure). FEV1 AUC 0–4 h was significantly higher for QVA149 versus placebo and tiotropium at Day 1 and Week 6 (all p < 0.001). Rescue medication use was significantly lower with QVA149 versus placebo (p < 0.001) and tiotropium (p = 0.002). Incidence rate of adverse events was similar across all the treatment groups (QVA 149: 35.0%; tiotropium: 35.5%; placebo: 39.4%). Conclusion The BLAZE study provides evidence that the improved lung function with QVA149 translates into greater relief of breathlessness and improved patient-reported outcomes. Reference Bateman et al. Eur Respir J. 2013 May 30. Vogelmeier et al. Lancet Respir Med. 2013; 1:51–60.

P234 QVA149 once daily improves lung function, dyspnoea and health status independent of prior medications and disease severity: the SHINE study

Introduction QVA149 is a novel, inhaled, once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and the long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) in development for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The SHINE study compared the effects of QVA149 110/50 µg, indacaterol 150 µg, glycopyrronium 50 µg, tiotropium 18 µg and placebo in patients with COPD.1 Here, we present the data on improvements in lung function (forced expiratory volume in 1 second area under the curve [FEV1 AUC5 min-4 h] and trough FEV1), transition dyspnoea index (TDI) and St George’s Respiratory Questionnaire (SGRQ - total score) by prior medication use and COPD disease severity subgroups. Methods In this 26-week, multicentre, double-blind, parallel-group, placebo- and active-controlled (open-label tiotropium) study, patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 and FEV1 ≥30% to <80% predicted) and a smoking history of ≥10 pack-years were randomised to receive once-daily QVA149, indacaterol, glycopyrronium, tiotropium or placebo (2:2:2:2:1). Results Of the 2144 patients (mean age 63.9 years; mean FEV1 post-bronchodilator 55.2% predicted) who were randomised (QVA149 [n = 475], indacaterol [n = 477], glycopyrronium [n = 475], tiotropium [n = 483] and placebo [n = 234]), 89.1% completed the study. QVA149 showed significant improvements in lung function, dyspnoea and health status compared with placebo in patient subgroups based on prior medication use and COPD disease severity (Table 1). Additionally, FEV1 AUC5 min-4 hwas significantly improved for QVA149 versus placebo (p < 0.001) regardless of the prior medication use and disease severity. Conclusion With once-daily QVA149, significant improvements were seen in both moderate and severe COPD patients and independent of medications used before recruitment and randomisation into the SHINE study. Reference Bateman et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013 May 30. [Epub ahead of print]. Abstract P234 Table 1. Lung function, dyspnoea and health status improvements in QVA149 vs placebo — subgroup analyses based on prior medicationuse and disease severity. 1 LSM (SE) treatment difference of QVA149 vs placebo FEV1AUC5min-4h(L) Trough FEV1(L) TDI total score SGRQ total score Prior medication use β-agonist plus steroid 0.34 (0.030)*** 0.19 (0.030)*** 1.21 (0.406)** –4.09 (1.705)* LABA 0.36 (0.059)*** 0.25 (0.058)*** 0.71 (0.798)ns –0.34 (3.103)ns LAMA 0.33 (0.028)*** 0.22 (0.029)*** 1.48 (0.443)*** –5.94 (1.770)*** SABA 0.37 (0.032)*** 0.22 (0.031)*** 1.29 (0.430)** –3.10 (1.780)ns SAMA 0.30 (0.074)*** 0.18 (0.073)* 2.27 (1.135)* –3.24 (4.495)ns β-agonist plus anticholinergic 0.31 (0.075)*** 0.08 (0.079)ns 1.13 (1.222)ns –4.66 (4.935)ns None 0.30 (0.033)*** 0.17 (0.034)*** 0.97 (0.500)ns –2.30 (2.198)ns COPD severity Moderate 0.37 (0.021)*** 0.24 (0.021)*** 1.17 (0.294)*** –2.74 (1.257)* Severe 0.26 (0.031)*** 0.12 (0.031)*** 1.00 (0.433)* –3.77 (1.840)* ***P<0.001 **;P<0.01; *P<0.05; ns, non-significant LSM, least squares mean; SABA,short-acting β2-agonist; SAMA, short-acting muscarinic antagonist; SE, standard error