The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma
<p>Abstract</p> <p/> <p>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.</p> <p>Me...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2010-03-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/11/1/26 |
| _version_ | 1811335329664204800 |
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| author | Macdonald Alex J Petavy Frank Singh Dave Lazaar Aili L O'Connor Brian J |
| author_facet | Macdonald Alex J Petavy Frank Singh Dave Lazaar Aili L O'Connor Brian J |
| author_sort | Macdonald Alex J |
| collection | DOAJ |
| description | <p>Abstract</p> <p/> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma.</p> <p>Trial Registration</p> <p>This study is registered on clinicaltrials.gov NCT00380354</p> |
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| format | Article |
| id | doaj.art-acc7146a5a2c4dfb95e6574a45a65406 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-04-13T17:22:32Z |
| publishDate | 2010-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-acc7146a5a2c4dfb95e6574a45a654062022-12-22T02:37:55ZengBMCRespiratory Research1465-99212010-03-011112610.1186/1465-9921-11-26The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthmaMacdonald Alex JPetavy FrankSingh DaveLazaar Aili LO'Connor Brian J<p>Abstract</p> <p/> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>GSK256066 demonstrated a protective effect on the EAR and LAR. This is the first inhaled PDE4 inhibitor to show therapeutic potential in asthma.</p> <p>Trial Registration</p> <p>This study is registered on clinicaltrials.gov NCT00380354</p>http://respiratory-research.com/content/11/1/26 |
| spellingShingle | Macdonald Alex J Petavy Frank Singh Dave Lazaar Aili L O'Connor Brian J The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma Respiratory Research |
| title | The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma |
| title_full | The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma |
| title_fullStr | The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma |
| title_full_unstemmed | The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma |
| title_short | The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma |
| title_sort | inhaled phosphodiesterase 4 inhibitor gsk256066 reduces allergen challenge responses in asthma |
| url | http://respiratory-research.com/content/11/1/26 |
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