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
- William W Busse1,
- Paul M O'Byrne2,
- Eugene R Bleecker3,
- Jan Lötvall4,
- Ashley Woodcock5,
- Leslie Andersen6,
- Wesley Hicks7,
- Jodie Crawford8,
- Loretta Jacques7,
- Ludovic Apoux9,
- Eric D Bateman10
- 1Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA
- 2Michael G DeGroote School of Medicine, Hamilton, Ontario, Canada
- 3Center for Genomics and Personalized Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
- 4Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden
- 5Institute of Inflammation and Repair, University of Manchester, Manchester, UK
- 6Respiratory Medicines Development Center, GlaxoSmithKline, Raleigh-Durham, North Carolina, USA
- 7Respiratory Medicine Development Centre, GlaxoSmithKline, London, UK
- 8Quantitative Sciences Division, GlaxoSmithKline, London, UK
- 9Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, London, UK
- 10Department of Medicine, University of Cape Town, Cape Town, South Africa
- Correspondence to Professor William W Busse, Department of Medicine, University of Wisconsin, K4/910 CSC, 600 Highland Avenue, Madison, WI 53792, USA;
- Received 21 August 2012
- Revised 2 January 2013
- Accepted 21 January 2013
- Published Online First 25 February 2013
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.
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