The 5‐lipoxygenase‐activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma. Issue 2 (18th January 2013)

• Record Type: Journal Article
• Authors: Kent, S. E.; Boyce, M.; Diamant, Z.; Singh, D.; O'Connor, B. J.; Saggu, P. S.; Norris, V.
• Is Part Of: Clinical & experimental allergy. Volume 43:Issue 2(2013:Feb.)
• Page Start: 177
• Page End: 186
• Publication Date: 2013-01-18
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12002
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" xml:lang="en" id="cea12002-abs-0001"> <title>Summary</title> <sec id="cea12002-sec-0001" sec-type="section"> <title>Background</title> <p>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).</p> </sec> <sec id="cea12002-sec-0002" sec-type="section"> <title>Objective</title> <p>To assess the effect of GSK2190915 on the allergen‐induced asthmatic responses.</p> </sec> <sec id="cea12002-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="cea12002-sec-0004" sec-type="section"> <title>Results</title> <p>GSK2190915 attenuated the early (0–2 h) and late (4–10 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 FEV<sub>1</sub> 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 FEV<sub>1</sub> LAR was 0.229 L (0.041, 0.417).</p> <p>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 LTB<sub>4</sub> by > 90% on Days 4 and 6. There was no effect on methacholine PC<sub>20</sub> post allergen. GSK2190915 was generally well tolerated.</p> </sec> <sec id="cea12002-sec-0005" sec-type="section"> <title>Conclusion and Clinical Relevance</title> <p>GSK2190915 shows potential as a treatment for patients with asthma.</p> </sec> </abstract>