Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD.
BACKGROUND
Indacaterol is a long-acting inhaled beta(2)-agonist (LABA) for the treatment of chronic obstructive pulmonary disease (COPD). In previous studies, indacaterol provided 24 h bronchodilation on once-daily dosing with a fast onset of action. This study compared the efficacy and safety of indacaterol with the twice-daily LABA formoterol and placebo over 1 year.


METHODS
Patients with moderate to severe COPD were randomised to receive once-daily indacaterol 300 microg (n=437) or 600 microg (n=428), twice-daily formoterol 12 microg (n=435) or placebo (n=432) for 52 weeks in a double-blind double-dummy parallel group study. The primary efficacy variable was forced expiratory volume in 1 s (FEV(1)) measured 24 h postdose after 12 weeks (indacaterol vs placebo). Other outcomes included dyspnoea (transition dyspnoea index, TDI), use of as-needed salbutamol, symptom-based measures recorded on diary cards, exacerbations, health status (St George's Respiratory Questionnaire), BODE index (body mass index, obstruction, dyspnoea, exercise), safety and tolerability.


RESULTS
Indacaterol increased 24 h postdose FEV(1) after 12 weeks by 170 ml (both doses) versus placebo and by 100 ml versus formoterol (all p<0.001). These significant differences were maintained at 52 weeks. Symptomatic outcomes were improved compared with placebo with all active treatments, and indacaterol was more effective than formoterol in improving TDI score and reducing the need for as-needed salbutamol. Indacaterol was well tolerated and had a good overall safety profile, including minimal impact on QTc interval and systemic beta(2)-mediated events.


CONCLUSIONS
Once-daily indacaterol is an effective 24 h bronchodilator that improves symptoms and health status and confers clinical improvements over a twice-daily 12 h LABA as a treatment for patients with moderate to severe COPD.


BACKGROUND
NCT 00393458.
Department of Respiratory Diseases, Aarhus University Hospital, Aarhus, Denmark. ronadahl@rm.dk
Ronald
R
Dahl
Kian Fan
KF
Chung
Roland
R
Buhl
Helgo
H
Magnussen
Vladimir
V
Nonikov
Damon
D
Jack
Patricia
P
Bleasdale
Roger
R
Owen
Mark
M
Higgins
Benjamin
B
Kramer
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D007189:Indans; D015363:Quinolones; C510790:indacaterol; D000068759:Formoterol Fumarate