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 (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(1) 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(1) 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 LTB(4) by > 90% on Days 4 and 6. There was no effect on methacholine PC(20) post allergen. GSK2190915 was generally well tolerated. CONCLUSION AND CLINICAL RELEVANCE: GSK2190915 shows potential as a treatment for patients with asthma.
