The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma

Sukh Singh, Dave Singh, Frank Petavy, Alex J. Macdonald, Aili L. Lazaar, Brian J. O'Connor

    Research output: Contribution to journalArticlepeer-review

    Abstract

    GSK256066 is a selective phosphodiesterase 4 inhibitor that can be given by inhalation, minimising the potential for side effects. We evaluated the effects of GSK256066 on airway responses to allergen challenge in mild asthmatics.Methods: In a randomised, double blind, cross-over study, 24 steroid naive atopic asthmatics with both early (EAR) and late (LAR) responses to inhaled allergen received inhaled GSK256066 87.5 mcg once per day and placebo for 7 days, followed by allergen challenge. Methacholine reactivity was measured 24 h post-allergen. Plasma pharmacokinetics were measured. The primary endpoint was the effect on LAR.Results: GSK256066 significantly reduced the LAR, attenuating the fall in minimum and weighted mean FEV1 by 26.2% (p = 0.007) and 34.3% (p = 0.005) respectively compared to placebo. GSK256066 significantly reduced the EAR, inhibiting the fall in minimum and weighted mean FEV1 by 40.9% (p = 0.014) and 57.2% (p = 0.014) respectively compared to placebo. There was no effect on pre-allergen FEV1 or methacholine reactivity post allergen. GSK256066 was well tolerated, with low systemic exposure; plasma levels were not measurable after 4 hours in the majority of subjects.Conclusions: GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma.Trial Registration: This study is registered on clinicaltrials.gov NCT00380354. © 2010 Singh et al; licensee BioMed Central Ltd.
    Original languageEnglish
    Article number26
    JournalRespiratory research
    Volume11
    DOIs
    Publication statusPublished - 1 Mar 2010

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