QVA149 demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease.
BACKGROUND
This randomised, double-blind, placebo controlled, four-period crossover study assessed the efficacy and safety of once-daily QVA149, a dual bronchodilator consisting of the long-acting β2-agonist indacaterol and the long-acting muscarinic antagonist glycopyrronium (NVA237), in patients with moderate to severe chronic obstructive pulmonary disease (COPD).


METHODS
Patients (N=154) were randomly assigned to receive QVA149 (indacaterol/NVA237) 300/50 μg, indacaterol 300 μg, indacaterol 600 μg, or placebo, once daily for 7 days with a 7-day washout period between each treatment. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) (mean of 23 h 15 min and 23 h 45 min post-dose values) on day 7. Other endpoints included trough FEV1 on day 1, individual time point FEV1 and monitoring and recording of all adverse events.


RESULTS
A total of 135 (87.7%) patients completed the study (all randomly assigned patients: mean age 61.7 years, 61.4% male, post-bronchodilator FEV1 52.2% predicted, FEV1/forced vital capacity 47.6%). The estimated treatment difference (95% CI) for trough FEV1 on day 7 between QVA149 and placebo was 226 ml (192 to 260; p<0.001). The estimated treatment difference between QVA149 and indacaterol 300 and 600 μg was 123 ml (89 to 157; p<0.001) and 117 ml (83 to 150; p<0.001), respectively. The improvements in mean trough FEV1 exceeded the predefined minimal clinically important differences of 100–140 ml for QVA149 versus placebo and indacaterol. Similar results were observed on day 1. All treatments were well tolerated.


CONCLUSIONS
QVA149 demonstrated rapid and sustained bronchodilation with significant improvements compared with indacaterol monotherapy and placebo in patients with COPD.


BACKGROUND
NCT00570778.
van Noord
Jan A
JA
Department of Respiratory Diseases, Atrium Medisch Centrum, Heerlen, The Netherlands. j.a.vannoord@atriummc.nl
Buhl
Roland
R
Laforce
Craig
C
Martin
Carmen
C
Jones
Francis
F
Dolker
Michael
M
Overend
Tim
T
D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004812:Epidemiologic Methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006024:Glycopyrrolate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D001993:Bronchodilator Agents; D004338:Drug Combinations; D007189:Indans; D015363:Quinolones; C554862:indacaterol-glycopyrronium combination; C510790:indacaterol; D006024:Glycopyrrolate