title: Efficacy and tolerability of indacaterol 75 μg once daily in patients aged ≥40 years with chronic obstructive pulmonary disease: results from 2 double-blind, placebo-controlled 12-week studies.
abstract: BACKGROUND
  Indacaterol is the first once-daily, long-acting, inhaled β(2)-agonist bronchodilator for maintenance treatment of chronic obstructive pulmonary disease (COPD). Two studies (previously reported in a Congress abstract) were performed in 2010 to provide efficacy and tolerability data to support the application for approval in the United States of indacaterol 75 μg once daily, a dose lower than that previously investigated in most studies.
  
  
  OBJECTIVE
  The primary objective was to evaluate the efficacy of indacaterol 75 μg once daily in terms of 24-hour post-dose ("trough") forced expiratory volume in the first second of respiration (FEV(1)) compared with placebo after 12 weeks of treatment.
  
  
  METHODS
  Patients with moderate to severe COPD were randomized to receive double-blind treatment with indacaterol 75 μg once daily (n = 163 and 159) or placebo (n = 160 and 159) for 12 weeks. In addition to trough FEV(1) after 12 weeks, rescue albuterol use, health status (St. George's Respiratory Questionnaire [SGRQ]), and tolerability were evaluated. Clinically relevant differences between active and placebo treatments were defined as ≥120 mL for trough FEV(1) and a decrease of ≥4 units in SGRQ total score.
  
  
  RESULTS
  Of patients enrolled in the 2 studies, 54% were men, and 90% and 94% were white, with mean age 64 and 61 years. Mean duration of COPD was 7 years; smoking history was 52 pack-years; and 45% and 37% of patients were receiving inhaled corticosteroid therapy. At week 12, indacaterol demonstrated clinically relevant bronchodilator efficacy, increasing trough FEV(1) by ≥120 mL versus placebo (P < 0.001), with significant bronchodilation maintained at all time points from 5 minutes to 24 hours post-dose. Over 12 weeks, relative to placebo, in patients receiving indacaterol therapy, rescue albuterol use was reduced by 1.2 and 0.7 puffs per day (P < 0.01), and the percentage of rescue-free days was increased by 13.7 and 8.4 (P < 0.01). At week 12, the SGRQ total score differed in the indacaterol group versus the placebo group by -3.8 and -3.6, respectively (P ≤ 0.01). Adverse events were reported for 49% and 45% of patients receiving indacaterol therapy, and for 46% and 41% receiving placebo.
  
  
  CONCLUSIONS
  Compared with placebo, indacaterol 75 μg once daily provided statistically significant and clinically relevant 24-hour bronchodilation and was well tolerated. In patients receiving indacaterol, the reduction in rescue albuterol use was statistically significant. Changes in health status also were statistically significant compared with placebo, although the differences of 3.6 and 3.8 units were below the predefined 4-unit level of clinical relevance. The results of these studies suggest that indacaterol 75 μg once daily is an effective maintenance treatment in patients with moderate to severe COPD. ClinicalTrials.gov identifiers: NCT01072448 and NCT01068600.
authors.affiliation: Clinical Research Institute of Southern Oregon PC, Medford, Oregon 97504, USA. ekerwin@allergyasthmaso.com
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.forename: Mark H
authors.initials: MH
authors.lastname: Gotfried
authors.forename: David
authors.initials: D
authors.lastname: Lawrence
authors.forename: Cheryl
authors.initials: C
authors.lastname: Lassen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Kramer
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage; D000704:Analysis of Variance; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D007189:Indans; D010919:Placebos; D015363:Quinolones; C510790:indacaterol; D000420:Albuterol