Inhaled fluticasone furoate/vilanterol does not affect hypothalamic-pituitary-adrenal axis function in adolescent and adult asthma: randomised, double-blind, placebo-controlled study

Authors


  • Authorship and contributorship

    A.A., W.H and L.J. developed the design and concept of the study, and A.A. was the study pharmacokineticist. J.C. and I.S. were study Principal Investigators at their respective investigational sites. R.T. was the clinical study investigation lead; N.G. was the lead statistical contact.

  • Ethics

    The study was approved by local ethics review committees and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from each patient prior to the performance of any study-specific procedures.

  • Conflict of interest

    J.C. has received investigator and travel fees for his role in conducting multicentre clinical trials organised by GlaxoSmithKline, administered by his employer facility IPS Research, which has also received site funding and support in association with such trials, which include the study described in this work. I.S. declares no conflicts of interest.A.A., R.T., W.H., N.G. and L.J. are employees of and hold stock/shares in GlaxoSmithKline. All authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors, had full access to and interpreted the data, and wrote the manuscript. All authors vouch for the accuracy and completeness of the data and the data analysis.

  • Funding

    This study was funded by GlaxoSmithKline (GSK study number HZA106851; http://www.clinicaltrials.gov registration number NCT01086410).

Abstract

Introduction

Fluticasone 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.

Objectives

To 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.

Methods

One 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.

Results

Non-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.

Conclusions

FF/VI was found to be non-inferior to placebo on HPA axis function, with no indication of significant cortisol suppression after 42 days.

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