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

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.

• Authors: Ann Allen, Isabelle Schenkenberger, Roopa Trivedi, Jeremy Cole, Wesley Hicks, Nadeem Gul, Loretta Jacques
• Journal: The clinical respiratory journal (Clin Respir J) Vol. 7 Issue 4 Pg. 397-406 (Oct 2013) ISSN: 1752-699X [Electronic] England
• PMID: 23578031 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Androstadienes
• Benzyl Alcohols
• Chlorobenzenes
• Glucocorticoids
• Placebos
• vilanterol
• fluticasone furoate
• Hydrocortisone

Topics

• Administration, Inhalation
• Adolescent
• Adult
• Aged
• Androstadienes (administration & dosage, adverse effects)
• Asthma (drug therapy)
• Benzyl Alcohols (administration & dosage, adverse effects)
• Child
• Chlorobenzenes (administration & dosage, adverse effects)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Glucocorticoids (administration & dosage, adverse effects)
• Humans
• Hydrocortisone (blood)
• Hypothalamo-Hypophyseal System (drug effects)
• Male
• Middle Aged
• Pituitary-Adrenal System (drug effects)
• Placebos
• Treatment Outcome
• Young Adult