• Ann Allen, Isabelle Schenkenberger, Roopa Trivedi, Jeremy Cole, Wesley Hicks, Nadeem Gul, and Loretta Jacques.
• Clinical Pharmacology Modelling and Simulation, GlaxoSmithKline, Stevenage, UK.
• Clin Respir J. 2013 Oct 1;7(4):397-406.

IntroductionFluticasone furoate (FF) is a novel inhaled corticosteroid with 24-h activity. FF is in development as a once-daily treatment for asthma as monotherapy and in combination with vilanterol (VI), a long-acting β2 agonist. Corticosteroids can have systemic effects on hypothalamic-pituitary-adrenal (HPA) axis function, potentially resulting in cortisol suppression.ObjectivesTo assess the effect of FF/VI compared with placebo on the HPA axis by evaluating 24-h weighted mean serum cortisol levels in adolescent and adult patients with persistent asthma.MethodsOne hundred eighty-five patients with >12 weeks history of asthma were randomised in a 4:4:4:1 ratio to one of two once-daily FF/VI treatments (100/25 μg or 200/25 μg), placebo or an active control group that received inhaled placebo plus one prednisolone 10 mg capsule daily for the last 7 days of the study. Twenty-four-hour serum and urinary cortisol was measured at baseline and on day 42.ResultsNon-inferiority in 24-h weighted mean serum cortisol after 6 weeks of treatment with once-daily FF/VI at either strength was shown. Treatment ratios [95% confidence interval (CI)] to placebo for FF/VI 100/25 μg [0.99 (0.87-1.12)] or FF/VI 200/25 μg [0.97 (0.86-1.10)] indicated non-inferiority of both FF/VI doses to placebo as the lower limit of the 95% CI was greater than the predefined 0.8. Prednisolone substantially reduced 24-h weighted mean serum cortisol [treatment ratio to placebo 0.34 (0.28-0.41)]. FF/VI was well-tolerated, and no safety concerns were identified.ConclusionsFF/VI was found to be non-inferior to placebo on HPA axis function, with no indication of significant cortisol suppression after 42 days.© 2013 John Wiley & Sons Ltd.

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