title: Safety and tolerability of indacaterol in asthma: a randomized, placebo-controlled 28-day study.
abstract: The safety and tolerability of indacaterol, a novel once-daily beta(2)-agonist bronchodilator with a fast onset of action, were assessed in 156 asthma patients in a multicentre, randomized, double-blind, placebo-controlled study. Patients received indacaterol 200, 400 or 600 microg or placebo once daily for 28 days. Adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, spirometry and physical examinations were monitored. Indacaterol pharmacokinetics were assessed. There was no evidence of dose-related increases in AE incidence or clinically significant hypokalaemia or hyperglycaemia in indacaterol-treated patients. Mean pulse rate changes were minor in any group, with maximum 1-h post-dose changes from baseline of -3.7, -3.3 and -2.2 bpm for indacaterol 200, 400 and 600 microg, respectively, and -2.9 bpm for placebo. Mean QTc interval was similar between groups; change from baseline >60 ms occurred in only two patients. Mean FEV(1) increased after the first indacaterol dose; baseline-adjusted pre-dose (trough) values remained >or=166 mL higher than placebo at all subsequent visits, supporting a 24-h bronchodilator effect. Pre-dose (but not post-dose) serum indacaterol concentrations indicated a slight trend for accumulation. Once-daily indacaterol 200-600 microg has a favourable therapeutic index. It is well tolerated, and is not associated with any adverse cardiac or metabolic effects, while providing effective 24-h bronchodilation.
authors.affiliation: Pulmonology Research Institute, Parkovaya Street, 32/61, 105077 Moscow, Russian Federation. chuchalin@hotmail.com
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Chuchalin
authors.forename: Alla N
authors.initials: AN
authors.lastname: Tsoi
authors.forename: Kai
authors.initials: K
authors.lastname: Richter
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.forename: P B
authors.initials: PB
authors.lastname: Luursema
authors.forename: Ray
authors.initials: R
authors.lastname: Cameron
authors.forename: Weibin
authors.initials: W
authors.lastname: Bao
authors.forename: Mark
authors.initials: M
authors.lastname: Higgins
authors.forename: Ralph
authors.initials: R
authors.lastname: Woessner
authors.forename: Andre
authors.initials: A
authors.lastname: van As
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013147:Spirometry / Q000379:methods; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D007189:Indans; D015363:Quinolones; C510790:indacaterol