title: A cumulative dose, safety and tolerability study of arformoterol in pediatric subjects with stable asthma.
abstract: OBJECTIVE
  Short-acting β(2) -agonists (SABAs) are recommended for treating acute pediatric asthma. The long-acting β(2) -agonist (LABA) arformoterol is approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Arformoterol acts rapidly, is delivered via nebulization, and, as such, raises concerns from the FDA over possible off-label use in acute asthma in children. As a step to investigate this issue, this study evaluated the safety and tolerability of three consecutive doses of arformoterol administered over 1 hr in children with stable asthma.
  
  
  METHODS
  This study consisted of a double-blind, crossover period in which subjects (ages 2-11 years) with stable asthma were randomized to three consecutive nebulized doses of arformoterol (7.5 µg/dose) or levalbuterol (0.63 mg/dose) administered over 1-hr (0, 30, and 60 min) followed by an open-label period with three consecutive doses of arformoterol (15 µg/dose) administered over 1 hr. Endpoints were change in heart rate, blood pressure, and serum potassium and glucose levels. Other endpoints included adverse events and pulmonary function.
  
  
  RESULTS
  There were no clinically important mean changes from pre-dose in heart rate, blood pressure, or serum glucose levels, across treatment groups. Substantial declines in serum potassium levels were observed both 2 and 6 hr post-dosing. Two subjects had declines to 2.8 mEq/L and 2.9 mEq/L 2-hr post-dosing. Adverse events were infrequent and differences in forced expiratory volume in 1 sec and peak expiratory flow across treatment groups were not clinically meaningful.
  
  
  CONCLUSIONS
  In this study, in children with stable asthma, three consecutive doses of arformoterol (7.5 and 15 µg) and levalbuterol were overall well tolerated. Nonetheless, serum potassium levels demonstrated substantial mean declines after dosing. These findings do not address or support the safety and tolerability of arformoterol use in acute exacerbations of asthma in children.
authors.affiliation: Sunovion Pharmaceuticals Inc., 84 Waterford Drive, Marlborough, MA 01752, USA. joseph.hinkle@sunovion.com
authors.forename: J
authors.initials: J
authors.lastname: Hinkle
authors.forename: J
authors.initials: J
authors.lastname: Hinson
authors.forename: E
authors.initials: E
authors.lastname: Kerwin
authors.forename: E
authors.initials: E
authors.lastname: Goodwin
authors.forename: K
authors.initials: K
authors.lastname: Sciarappa
authors.forename: L
authors.initials: L
authors.lastname: Curry
authors.forename: J P
authors.initials: JP
authors.lastname: Hanrahan
mesh_terms: D000420:Albuterol / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009330:Nebulizers and Vaporizers; D056687:Off-Label Use; D011188:Potassium / Q000097:blood
chemical_list: D001786:Blood Glucose; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000420:Albuterol; D011188:Potassium; D000068759:Formoterol Fumarate