Michelle Henley

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

Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD

Two, once daily (q.d.) inhaled bronchodilators are available for the treatment of chronic obstructive pulmonary disease (COPD): the &bgr;2-agonist indacaterol and the anticholinergic tiotropium. This blinded study compared the efficacy of these two agents and assessed their safety and tolerability. Patients with moderate-to-severe COPD were randomised to treatment with indacaterol 150 μg q.d. (n=797) or tiotropium 18 μg q.d. (n=801) for 12 weeks. After 12 weeks, the two treatments had similar overall effects on “trough” (24 h post-dose) forced expiratory volume in 1 s. Indacaterol-treated patients had greater improvements in transition dyspnoea index (TDI) total score (least squares means 2.01 versus 1.43; p<0.001) and St George’s Respiratory Questionnaire (SGRQ) total score (least squares means 37.1 versus 39.2; p<0.001; raw mean change from baseline -5.1 versus -3.0), and were significantly more likely to achieve clinically relevant improvements in these end-points (indacaterol versus tiotropium odds ratios of 1.49 for TDI and 1.43 for SGRQ, both p<0.001). Adverse events were recorded for 39.7% and 37.2% of patients in the indacaterol and tiotropium treatment groups, respectively. The most frequent adverse events were COPD worsening, cough and nasopharyngitis. Both bronchodilators demonstrated spirometric efficacy. The two treatments were well tolerated with similar adverse event profiles. Compared with tiotropium, indacaterol provided significantly greater improvements in clinical outcomes.

Effect of QVA149 on lung volumes and exercise tolerance in COPD patients: The BRIGHT study

INTRODUCTION QVA149 is a novel, inhaled, once-daily dual bronchodilator containing a fixed-dose combination of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), for the treatment of chronic obstructive pulmonary disease (COPD). This study evaluated the effects of QVA149 on exercise tolerance, hyperinflation, lung function and lung volumes versus placebo and tiotropium. METHODS Patients with moderate-to-severe COPD were randomized to QVA149 110/50 μg, placebo or tiotropium 18 μg once daily in a blinded, 3-period crossover study for 3 weeks. The primary endpoint was exercise endurance time at Day 21 for QVA149 versus placebo. RESULTS Eighty-five patients were randomized; 86% completed the study. QVA149 significantly improved exercise endurance time at Day 21 compared with placebo (least squares mean treatment difference 60 s [p = 0.006]). No significant improvements in exercise endurance time at Day 21 between QVA149 and tiotropium were found. Dynamic inspiratory capacity (IC) at exercise isotime, trough forced expiratory volume in 1 s, residual volume and functional residual capacity showed significant improvements with QVA149 from Day 1 of treatment that were maintained throughout the study. The safety profiles were similar across groups. CONCLUSIONS In patients with moderate-to-severe COPD, once-daily QVA149 significantly improved exercise endurance time compared with placebo which was associated with sustained reductions of lung hyperinflation as indicated by significant improvement in IC at rest and during exercise. TRIAL REGISTRATION ClinicalTrials.gov NCT01294787. TAKE HOME MESSAGE Dual bronchodilation with QVA149 decreases lung hyperinflation and improves exercise tolerance and lung function in patients with moderate-to-severe COPD.

Effect of once‐daily indacaterol in a predominantly Chinese population with chronic obstructive pulmonary disease: A 26‐week Asia‐Pacific study

This study, in a predominantly Chinese population, investigated the efficacy and safety of a once‐daily (o.d.) inhaled ultra‐long‐acting β2‐agonist indacaterol for the treatment of moderate‐to‐severe chronic obstructive pulmonary disease (COPD).

Efficacy and safety of twice-daily glycopyrrolate in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation: the GEM1 study

Background The purpose of this study was to confirm the efficacy and safety of twice-daily glycopyrrolate 15.6 µg, a long-acting muscarinic antagonist, in patients with stable, symptomatic, chronic obstructive pulmonary disease (COPD) with moderate-to-severe airflow limitation. Methods The GEM1 study was a 12-week, multicenter, double-blind, parallel-group, placebo-controlled study that randomized patients with stable, symptomatic COPD with moderate-to-severe airflow limitation to twice-daily glycopyrrolate 15.6 µg or placebo (1:1) via the Neohaler® device. The primary objective was to demonstrate superiority of glycopyrrolate versus placebo in terms of forced expiratory volume in 1 second area under the curve between 0 and 12 hours post morning dose at week 12. Other outcomes included additional spirometric end points, transition dyspnea index, St George’s Respiratory Questionnaire, COPD Assessment Test, rescue medication use, and symptoms reported by patients via electronic diary. Safety was also assessed during the study. Results Of the 441 patients randomized (glycopyrrolate, n=222; placebo, n=219), 96% of patients completed the planned treatment phase. Glycopyrrolate demonstrated statistically significant (P<0.001) improvements in lung function versus placebo. Glycopyrrolate showed statistically significant improvement in the transition dyspnea index focal score, St George’s Respiratory Questionnaire total score, COPD Assessment Test score, rescue medication use, and daily total symptom score versus placebo at week 12. Safety was comparable between the treatment groups. Conclusion Significant improvement in lung function, dyspnea, COPD symptoms, health status, and rescue medication use suggests that glycopyrrolate is a safe and effective treatment option as maintenance bronchodilator in patients with stable, symptomatic COPD with moderate-to-severe airflow limitation.

P233 Efficacy and safety of once-daily glycopyrronium compared with blinded tiotropium in patients with COPD: the GLOW5 study

Background Glycopyrronium, a once-daily long-acting muscarinic antagonist (LAMA), has demonstrated a similar efficacy and safety profile to open-label tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).1 The GLOW5 study compared the efficacy and safety of glycopyrronium with blinded tiotropium. Methods In this multicentre, 12-week, blinded study, patients ≥ 40 years with moderate-to-severe COPD (post-bronchodilator FEV1 ≥ 30% and < 80% of the predicted normal, post-bronchodilator FEV1/FVC < 0.70) and a smoking history of ≥10 pack-years were randomised to glycopyrronium 50μg (via Breezhaler® device) or tiotropium 18μg (via HandiHaler® device). The primary objective was to demonstrate non-inferiority of glycopyrronium versus tiotropium for trough FEV1 at Week 12 (non-inferiority margin: –50 mL). Other endpoints included FEV1 area under the curve from 0 to 4 hours (AUC0–4hr) on Day 1, Transition Dyspnoea Index (TDI), St Georges Respiratory Questionnaire (SGRQ), rescue medication use, exacerbation rate, safety and tolerability. Results Of the 657 patients randomised, (glycopyrronium [n = 327]; tiotropium [n = 330]; mean age: 63.5 years, mean post-bronchodilator FEV1: 53.5% predicted), 95.9% completed the study. Glycopyrronium demonstrated non-inferiority to tiotropium for trough FEV1 at Week 12 (Least Squares Mean [LSM] = 1.41L for both the groups; 95% confidence interval [CI]: –0.032, 0.031L). Glycopyrronium had a rapid onset of bronchodilation in the morning as demonstrated by a higher FEV1 AUC0–4hr on Day 1 compared to tiotropium (LSM treatment difference [Td] = 58mL; p < 0.001). At Week 12, TDI total score (Td = –0.188; p = 0.385), SGRQ total score (Td = 0.65; p = 0.488) and percentage of days with no rescue medication use (Td = –1.5; p = 0.528) were comparable between the groups. No significant treatment difference was observed with respect to rate of moderate/severe COPD exacerbations per year (glycopyrronium 0.38 versus tiotropium 0.35 [rate ratio = 1.10, 95% CI: 0.62, 1.93]; p = 0.754). Overall, the incidence of adverse events was similar in the glycopyrronium (40.4%) and tiotropium (40.6%) groups. Conclusion Glycopyrronium and blinded tiotropium showed similar improvements in lung function, dyspnoea, health status, exacerbation rate and rescue medication use, with a similar safety and tolerability profile. Onset of bronchodilation with glycopyrronium was significantly more rapid following the first dose. Reference Kerwin, E. et al. Eur Resp J 2012;40:1106–1114.