title: Inhaled fluticasone furoate/vilanterol does not affect hypothalamic-pituitary-adrenal axis function in adolescent and adult asthma: randomised, double-blind, placebo-controlled study.
abstract: BACKGROUND
  Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24-h activity. FF is in development as a once-daily treatment for asthma as monotherapy and in combination with vilanterol (VI), a long-acting β2 agonist. Corticosteroids can have systemic effects on hypothalamic-pituitary-adrenal (HPA) axis function, potentially resulting in cortisol suppression.
  
  
  OBJECTIVE
  To assess the effect of FF/VI compared with placebo on the HPA axis by evaluating 24-h weighted mean serum cortisol levels in adolescent and adult patients with persistent asthma.
  
  
  METHODS
  One hundred eighty-five patients with >12 weeks history of asthma were randomised in a 4:4:4:1 ratio to one of two once-daily FF/VI treatments (100/25 μg or 200/25 μg), placebo or an active control group that received inhaled placebo plus one prednisolone 10 mg capsule daily for the last 7 days of the study. Twenty-four-hour serum and urinary cortisol was measured at baseline and on day 42.
  
  
  RESULTS
  Non-inferiority in 24-h weighted mean serum cortisol after 6 weeks of treatment with once-daily FF/VI at either strength was shown. Treatment ratios [95% confidence interval (CI)] to placebo for FF/VI 100/25 μg [0.99 (0.87-1.12)] or FF/VI 200/25 μg [0.97 (0.86-1.10)] indicated non-inferiority of both FF/VI doses to placebo as the lower limit of the 95% CI was greater than the predefined 0.8. Prednisolone substantially reduced 24-h weighted mean serum cortisol [treatment ratio to placebo 0.34 (0.28-0.41)]. FF/VI was well-tolerated, and no safety concerns were identified.
  
  
  CONCLUSIONS
  FF/VI was found to be non-inferior to placebo on HPA axis function, with no indication of significant cortisol suppression after 42 days.
authors.affiliation: Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Stevenage, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Allen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schenkenberger
authors.forename: Roopa
authors.initials: R
authors.lastname: Trivedi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Cole
authors.forename: Wesley
authors.initials: W
authors.lastname: Hicks
authors.forename: Nadeem
authors.initials: N
authors.lastname: Gul
authors.forename: Loretta
authors.initials: L
authors.lastname: Jacques
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D010919:Placebos; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D005938:Glucocorticoids; D010919:Placebos; C550468:vilanterol; C523187:fluticasone furoate; D006854:Hydrocortisone
keywords: asthma; cortisol; fluticasone furoate; hypothalamic-pituitary-adrenal axis; inhaled corticosteroid; long-acting beta2 agonist; vilanterol