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Thorax 68:513-520 doi:10.1136/thoraxjnl-2012-202606
  • Asthma
  • Original article

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

Open Access
  1. Eric D Bateman10
  1. 1Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
  2. 2Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada
  3. 3Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
  4. 4Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden
  5. 5Institute of Inflammation and Repair, University of Manchester, Manchester, UK
  6. 6Respiratory Medicines Development Center, GlaxoSmithKline, Raleigh-Durham, North Carolina, USA
  7. 7Respiratory Medicine Development Centre, GlaxoSmithKline, London, UK
  8. 8Quantitative Sciences Division, GlaxoSmithKline, London, UK
  9. 9Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, London, UK
  10. 10Department of Medicine, University of Cape Town, Cape Town, South Africa
  1. Correspondence to Professor William W Busse, Department of Medicine, University of Wisconsin, K4/910 CSC, 600 Highland Avenue, Madison, WI 53792, USA; wwb{at}medicine.wisc.edu
  • Received 21 August 2012
  • Revised 2 January 2013
  • Accepted 21 January 2013
  • Published Online First 25 February 2013

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

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