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

Thorax. 2013 Jun;68(6):513-20. doi: 10.1136/thoraxjnl-2012-202606. Epub 2013 Feb 25.

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.

Keywords: Asthma.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-2 Receptor Antagonists / administration & dosage*
  • Adult
  • Androstadienes / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Benzyl Alcohols / administration & dosage*
  • Child
  • Chlorobenzenes / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Drug Tolerance
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Glucocorticoids / administration & dosage*
  • Humans
  • Male
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Adrenergic beta-2 Receptor Antagonists
  • Androstadienes
  • Benzyl Alcohols
  • Chlorobenzenes
  • Glucocorticoids
  • vilanterol
  • fluticasone furoate

Associated data

  • ClinicalTrials.gov/NCT01018186