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

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. In a randomised, double blind, cross-over study, 24 steroid naive ato...

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Bibliographic Details
Published in:Respiratory research 2010-03, Vol.11 (1), p.26-26, Article 26
Main Authors: Singh, Dave, Petavy, Frank, Macdonald, Alex J, Lazaar, Aili L, O'Connor, Brian J
Format: Article
Language:English
Subjects:
Adenylic acid
Administration, Inhalation
Allergens
Aminoquinolines - administration & dosage
Asthma
Asthma - diagnosis
Asthma - drug therapy
Bronchial Provocation Tests
Drug therapy
Female
Health aspects
Humans
Male
Middle Aged
Phosphodiesterase 4 Inhibitors
Risk factors
Sulfones - administration & dosage
Treatment Outcome
Young Adult
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Summary: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. 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. 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. GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma.
ISSN:1465-993X
1465-9921
1465-993X
DOI:10.1186/1465-9921-11-26