Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study.
BACKGROUND
Indacaterol is a novel, once-daily beta(2)-agonist in development for the treatment of asthma and chronic obstructive pulmonary disease. Studies were required to determine optimal dose(s) for continuing investigation.


OBJECTIVE
A dose-ranging study was undertaken to evaluate efficacy and safety of indacaterol.


METHODS
A total of 436 patients with persistent asthma receiving inhaled corticosteroids were randomized to 7 days treatment with once-daily indacaterol 50, 100, 200, or 400 microg via multi-dose dry-powder inhaler (MDDPI; Certihaler), indacaterol 400 microg via single-dose dry-powder inhaler (SDDPI), or placebo. Serial 24-h spirometry was performed on days 1 and 7. Vital signs, laboratory evaluations, and adverse events were monitored.


RESULTS
All doses of indacaterol increased the mean time-standardized area under the curve of forced expiratory volume in 1 s (FEV(1)) from 22 to 24 h postdose (P <or= 0.001 vs placebo) on days 1 and 7, with clinically relevant treatment-placebo differences of 240, 260, 350, 300, and 380 ml on day 1 and 230, 220, 320, 250, and 270 ml on day 7 for indacaterol 50, 100, 200, and 400 microg via MDDPI and 400 microg via SDDPI, respectively. All doses increased mean FEV(1) (P < 0.05 vs placebo) from 5 min to 24 h postdose on days 1 and 7. All doses were well tolerated. Most adverse events were mild-to-moderate in severity: most frequently reported were respiratory, thoracic, and mediastinal disorders.


CONCLUSIONS
Once-daily dosing with indacaterol provided sustained 24-h bronchodilation in patients with moderate-to-severe asthma, with a satisfactory overall safety profile. Indacaterol 200 microg appears the optimum dose, offering the best efficacy/safety balance.
Department of Pediatrics, University of North Carolina School of Medicine, North Carolina Clinical Research, Raleigh, NC 27607, USA.
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C
LaForce
M
M
Alexander
R
R
Deckelmann
L M
LM
Fabbri
Z
Z
Aisanov
R
R
Cameron
R
R
Owen
M
M
Higgins
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D015363:Quinolones / Q000008:administration & dosage*; D012016:Reference Values; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013147:Spirometry; D016896:Treatment Outcome
D007189:Indans; D015363:Quinolones; C510790:indacaterol