A dose-ranging study of indacaterol in obstructive airways disease, with a tiotropium comparison

SummaryThis dose-ranging study assessed the bronchodilator efficacy and tolerability of indacaterol, a novel once-daily inhaled β2-agonist, in subjects clinically diagnosed with COPD. Comparative data with tiotropium were collected.In the double-blind, core period of the study, 635 subjects with COPD (prebronchodilator FEV1⩾40% of predicted and ⩾1.0L; FEV1/FVC <70%) were randomized to receive indacaterol 50, 100, 200 or 400μg or placebo via multi-dose dry powder inhaler, or indacaterol 400μg via single-dose dry powder inhaler, once daily for 7 days. After completing double-blind treatment and washout, a subset of subjects from each treatment group entered an open-label extension and received tiotropium 18μg once daily for 8 days. The primary efficacy variable was the trough bronchodilator effect: standardized area under the FEV1 curve between 22 and 24h post-dose (FEV1 AUC22–24h) on Day 1.Clinically relevant improvements versus placebo in FEV1 AUC22–24h were seen for 400 and 200μg doses on Day 1 and all doses on Day 7. All indacaterol doses significantly (P<0.05) increased FEV1 from 5min to 24h post-dose; the 400 and 200μg doses were most effective. All doses were well tolerated. Indacaterol trough FEV1 levels compared favorably with the improvement seen by Day 8 in subjects treated with tiotropium in the open-label extension.The results confirm that indacaterol has a 24-h duration of bronchodilator effect and a fast onset of action in COPD and suggest that indacaterol could be an effective once-daily inhaled β2-agonist bronchodilator. Indacaterol demonstrated a good overall safety and tolerability profile

A blinded evaluation of the efficacy and safety of glycopyrronium, a once-daily long-acting muscarinic antagonist, versus tiotropium, in patients with COPD: the GLOW5 study

Abstract Background Two once-daily long-acting muscarinic antagonists (LAMAs) are currently available for the treatment of chronic obstructive pulmonary disease (COPD) – tiotropium and glycopyrronium. Previous studies have compared glycopyrronium with open-label tiotropium. In the GLOW5 study, we compare glycopyrronium with blinded tiotropium. Methods In this blinded, double-dummy, parallel group, 12-week study, patients with moderate-to-severe COPD were randomized 1:1 to glycopyrronium 50 μg once daily or tiotropium 18 μg once daily. The primary objective was to demonstrate the non-inferiority of glycopyrronium versus blinded tiotropium with respect to trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment (non-inferiority margin: –50 mL). Secondary objectives were to evaluate glycopyrronium versus tiotropium for other spirometric outcomes, breathlessness (Transition Dyspnea Index; TDI), health status (St George’s Respiratory Questionnaire; SGRQ), daily rescue medication use, COPD exacerbations and COPD symptoms over 12 weeks of treatment. Results 657 patients were randomized (glycopyrronium: 327; tiotropium: 330); 96% (630 patients) completed the study. Least squares mean trough FEV1 for both glycopyrronium and tiotropium was 1.405 L at Week 12, meeting the criterion for non-inferiority (mean treatment difference: 0 mL, 95% CI: –32, 31 mL). Glycopyrronium demonstrated rapid bronchodilation following first dose on Day 1, with significantly higher FEV1 at all time points from 0–4 h post-dose versus tiotropium (all p < 0.001). FEV1 area under the curve from 0–4 h (AUC0–4h) post-dose with glycopyrronium was significantly superior to tiotropium on Day 1 (p < 0.001) and was comparable to tiotropium at Week 12. Glycopyrronium demonstrated comparable improvements to tiotropium in TDI focal score, SGRQ total score, rescue medication use and the rate of COPD exacerbations (all p = not significant). Patients on glycopyrronium also had a significantly lower total COPD symptom score versus patients on tiotropium after 12 weeks (p = 0.035). Adverse events were reported by a similar percentage of patients receiving glycopyrronium (40.4%) and tiotropium (40.6%). Conclusion In patients with moderate-to-severe COPD, 12-week blinded treatment with once-daily glycopyrronium 50 μg or tiotropium 18 μg, provided similar efficacy and safety, with glycopyrronium having a faster onset of action on Day 1 versus tiotropium. Trial registration ClinicalTrial.gov, NCT0161332