The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma
(2013) In Clinical and Experimental Allergy 43(2). p.177-186- Abstract
- Background GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). Objective To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. Methods Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100 mg and placebo orally once daily for 5 days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. Results GSK2190915 attenuated the early (02 h) and late (410 h)... (More)
- Background GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). Objective To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. Methods Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100 mg and placebo orally once daily for 5 days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. Results GSK2190915 attenuated the early (02 h) and late (410 h) asthmatic responses to inhaled allergen compared with placebo. There was a statistically significant attenuation of the early asthmatic response (EAR) by GSK2190915; treatment difference of GSK2190915 vs. placebo for the minimum FEV1 EAR was 0.408 L (0.205, 0.611). There was a statistically significant attenuation of the late asthmatic response (LAR) by GSK2190915; the treatment difference of GSK2190915 vs. placebo for the minimum FEV1 LAR was 0.229 L (0.041, 0.417). There was a statistically significant attenuation of allergen-induced sputum eosinophil count on Day 4 following GSK2190915: mean treatment difference (95% CI) between GSK2190915 and placebo was -9.95% (-18.15%, -1.77%). Compared with placebo, GSK2190915 100 mg reduced median sputum LTB4 by > 90% on Days 4 and 6. There was no effect on methacholine PC20 post allergen. GSK2190915 was generally well tolerated. Conclusion and Clinical Relevance GSK2190915 shows potential as a treatment for patients with asthma. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3590181
- author
- Kent, S. E. ; Boyce, M. ; Diamant, Zuzana LU ; Singh, D. ; O'Connor, B. J. ; Saggu, P. S. and Norris, V.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 5-lipoxygenase-activating protein inhibitor, AM803, bronchial allergen, challenge, GSK2190915, leukotriene, sputum eosinophils
- in
- Clinical and Experimental Allergy
- volume
- 43
- issue
- 2
- pages
- 177 - 186
- publisher
- Wiley
- external identifiers
-
- wos:000313815300006
- scopus:84872561296
- ISSN
- 1365-2222
- DOI
- 10.1111/cea.12002
- language
- English
- LU publication?
- yes
- id
- 1f42eab4-63e4-4762-af8f-aceb3594fce8 (old id 3590181)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23331559
- date added to LUP
- 2016-04-01 11:00:34
- date last changed
- 2022-02-02 23:03:18
@article{1f42eab4-63e4-4762-af8f-aceb3594fce8,
abstract = {{Background GSK2190915, a potent 5-lipoxygenase-activating protein inhibitor, prevents the synthesis of leukotrienes and 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE). Objective To assess the effect of GSK2190915 on the allergen-induced asthmatic responses. Methods Nineteen eligible male subjects with mild asthma were enrolled in and completed this four-centre, double-blind, two-way crossover study (ClinicalTrials.gov NCT00748306). Subjects took GSK2190915 100 mg and placebo orally once daily for 5 days in randomized order. On Day 1 and 4 they had a methacholine challenge, on Day 3 they had an inhaled allergen challenge, and on Days 4 and 6 they had sputum induction. Results GSK2190915 attenuated the early (02 h) and late (410 h) asthmatic responses to inhaled allergen compared with placebo. There was a statistically significant attenuation of the early asthmatic response (EAR) by GSK2190915; treatment difference of GSK2190915 vs. placebo for the minimum FEV1 EAR was 0.408 L (0.205, 0.611). There was a statistically significant attenuation of the late asthmatic response (LAR) by GSK2190915; the treatment difference of GSK2190915 vs. placebo for the minimum FEV1 LAR was 0.229 L (0.041, 0.417). There was a statistically significant attenuation of allergen-induced sputum eosinophil count on Day 4 following GSK2190915: mean treatment difference (95% CI) between GSK2190915 and placebo was -9.95% (-18.15%, -1.77%). Compared with placebo, GSK2190915 100 mg reduced median sputum LTB4 by > 90% on Days 4 and 6. There was no effect on methacholine PC20 post allergen. GSK2190915 was generally well tolerated. Conclusion and Clinical Relevance GSK2190915 shows potential as a treatment for patients with asthma.}},
author = {{Kent, S. E. and Boyce, M. and Diamant, Zuzana and Singh, D. and O'Connor, B. J. and Saggu, P. S. and Norris, V.}},
issn = {{1365-2222}},
keywords = {{5-lipoxygenase-activating protein inhibitor; AM803; bronchial allergen; challenge; GSK2190915; leukotriene; sputum eosinophils}},
language = {{eng}},
number = {{2}},
pages = {{177--186}},
publisher = {{Wiley}},
series = {{Clinical and Experimental Allergy}},
title = {{The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma}},
url = {{http://dx.doi.org/10.1111/cea.12002}},
doi = {{10.1111/cea.12002}},
volume = {{43}},
year = {{2013}},
}