title: Efficacy, safety and pharmacokinetics of indacaterol in Caucasian and Japanese patients with chronic obstructive pulmonary disease: a comparison of data from two randomized, placebo-controlled studies.
abstract: BACKGROUND
  Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-adrenoceptor agonist that has been approved in the EU for the treatment of chronic obstructive pulmonary disease (COPD). Ethnic differences may influence the pharmacokinetics and pharmacodynamics of a drug, and it is therefore important to compare these parameters in different populations.
  
  
  OBJECTIVE
  To compare the efficacy, safety and pharmacokinetics of indacaterol between Caucasian and Japanese patients with COPD.
  
  
  METHODS
  Data from two randomized, double-blind, single-dose crossover, placebo-controlled studies in Caucasian and Japanese patients with moderate-to-severe COPD were compared. The two studies were similar in terms of study design, study population (inclusion/exclusion criteria), parameters examined and the indacaterol doses (150, 300 or 600 μg) tested. Efficacy (primary endpoint: 24-hour post-dose [trough] forced expiratory volume in 1 second [FEV1]), pharmacokinetics, and safety were assessed for 24 hours post-dose in each treatment period.
  
  
  RESULTS
  Fifty-one Caucasian (86.3% male; mean age 61.8 years) patients were randomized into the first study and 50 Japanese (92.0% male; mean age 67.2 years) patients were randomized into the second study; ≥90% of patients completed the studies. In both studies, 24-hour post-dose trough FEV1 was significantly higher for all indacaterol doses versus placebo (p<0.001), with clinically relevant differences of 140 and 130 mL for the lowest (150 μg) dose in the Caucasian and Japanese studies, respectively. In both studies, single doses of indacaterol provided improvements in FEV1 that were sustained for 24 hours (p<0.001 vs placebo at all time points). In both populations, the average maximum serum concentration (Cmax) of indacaterol was observed at the first sampling time point and pharmacokinetic profiles were similar between populations. The increase in exposure (Cmax and area under the serum concentration-time curve from time zero to 24 hours) with increasing indacaterol dose was similar in both populations. All indacaterol doses in both studies demonstrated similar safety profiles.
  
  
  CONCLUSIONS
  Indacaterol provided 24-hour bronchodilation with a fast onset of action and similar pharmacokinetic and safety profiles in Caucasian and Japanese patients. These findings suggest that ethnic factors do not influence the treatment of COPD with indacaterol.
authors.affiliation: Novartis Pharma KK, Tokyo, Japan. motoi.hosoe@novartis.com
authors.forename: Motoi
authors.initials: M
authors.lastname: Hosoe
authors.forename: Ralph
authors.initials: R
authors.lastname: Woessner
authors.forename: Soichiro
authors.initials: S
authors.lastname: Matsushima
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kramer
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use*; D000368:Aged; D044466:Asian People; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044465:White People
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; C510790:indacaterol