title: Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β2 agonist vilanterol administered once daily for 52 weeks in patients >=12 years old with asthma: a randomised trial.
abstract: BACKGROUND
  The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease.
  
  
  OBJECTIVE
  To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma.
  
  
  METHODS
  Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate.
  
  
  RESULTS
  On-treatment AEs were similar across groups (FF/VI 66-69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6-7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2-1.1 bpm FF/VI vs 5 bpm FP; Week 52).
  
  
  CONCLUSIONS
  FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern. CLINICALTRIALS.GOV: NCT01018186.
authors: Department of Medicine, University of Wisconsin, Madison, WI, USA. wwb@medicine.wisc.edu
authors: William W
authors: WW
authors: Busse
authors: Paul M
authors: PM
authors: O'Byrne
authors: Eugene R
authors: ER
authors: Bleecker
authors: Jan
authors: J
authors: Lötvall
authors: Ashley
authors: A
authors: Woodcock
authors: Leslie
authors: L
authors: Andersen
authors: Wesley
authors: W
authors: Hicks
authors: Jodie
authors: J
authors: Crawford
authors: Loretta
authors: L
authors: Jacques
authors: Ludovic
authors: L
authors: Apoux
authors: Eric D
authors: ED
authors: Bateman
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058672:Adrenergic beta-2 Receptor Antagonists / Q000008:administration & dosage*; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001592:Benzyl Alcohols / Q000008:administration & dosage*; D002648:Child; D002722:Chlorobenzenes / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D002722:Chlorobenzenes; D005938:Glucocorticoids; C550468:vilanterol; C523187:fluticasone furoate
keywords: Asthma