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 Busse, Paul M O'Byrne, Eugene R Bleecker, Jan Lötvall, Ashley Woodcock, Leslie Andersen, Wesley Hicks, Jodie Crawford, Loretta Jacques, Ludovic Apoux, Eric D Bateman, William W Busse, Paul M O'Byrne, Eugene R Bleecker, Jan Lötvall, Ashley Woodcock, Leslie Andersen, Wesley Hicks, Jodie Crawford, Loretta Jacques, Ludovic Apoux, Eric D Bateman
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.
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References
- Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention. Updated 2011. (accessed 16 Jul 2012).
- National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) 2007. NHLBI, August; 2007. NIH publication no. 08-4051. (accessed 16 Jul 2012).
- Colice GL. Emerging therapeutic options for asthma. Am J Manag Care 2011;(Suppl 3):S82–9
- Price D, Robertson A, Bullen K, et al. Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study. BMC Pulm Med 2010;10:1.
- Bateman ED, Bleecker ER, Busse W, et al. Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial. Resp Med 2012;106:642–50
- Bleecker ER, Bateman ED, Busse W, et al. Fluticasone furoate (FF), an inhaled corticosteroid (ICS), is efficacious in asthma patients symptomatic on low doses of ICS therapy. Eur Respir J 2010;36(Suppl 54):204s
- Busse W, Bleecker ER, Bateman ED, et al. Fluticasone furoate demonstrates efficacy in asthma patients symptomatic on medium doses of inhaled corticosteroid therapy: a randomised, placebo-controlled trial. Thorax 2012;67:35–41
- Lötvall J, Bateman ED, Bleecker ER, et al. 24-hour duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids. Eur Respir J 2012;40:570–9
- Sterling R, Lim J, Frith L, et al. Dose-related efficacy and optimal once-daily (OD) dosing interval of the long-acting beta2 agonist (LABA), vilanterol trifenatate (VI), in adults with persistent asthma. Respir Med 2012;106:1110–15
- Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59–99
- Chylack LT, Wolfe JK, Singer DM, et al. The lens opacities classification system III. Arch Ophthalmol 1993;111:831–6
- Flovent™ prescribing information 2010. (accessed 16 Jul 2012).
- Adams NP, Bestall JC, Jones P, et al. Fluticasone at different doses for chronic asthma in adults and children. Cochrane Database Syst Rev 2008;4:CD003534.
- Kurt E, Yildirim H, Kiraz N, et al. Oropharyngeal candidiasis with dry-powdered fluticasone propionate: 500 microg/day versus 200 microg/day. Allergol Immunopathol (Madr) 2008;36:17–20
- Derom E, Louis R, Tiesler C, et al. Effects of ciclesonide and fluticasone on cortisol secretion in patients with persistent asthma. Eur Respir J 2009;33:1277–86
- Kempsford R, Allen A, Kelly K, et al. A repeat dose, double-blind, placebo-controlled ‘Thorough QT/QTc study’ to assess the cardiac safety of fluticasone furoate (FF) and vilanterol (VI) administered in combination. Am J Respir Crit Care Med 2012;185:A2841
- Bjerregaard P. Premature beats in healthy subjects 40–79 years of age. Eur Heart J 1982;3:493–503
- Stinson JC, Pears JS, Williams AJ, et al. Use of 24 h ambulatory ECG recordings in the assessment of new chemical entities in healthy volunteers. Br J Clin Pharmac 1995;39:651–6
- Grimm W, Liedtke J, Muller H-H. Prevalence of potential noninvasive arrhythmia risk predictors in healthy, middle-aged persons. Ann Noninvasive Electrocardiol 2003;8:37–46
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