This is a randomised, double blind, placebo-controlled, two-way cross-over study to evaluate the effect of treatment with repeat dose GSK2190915, a 5-lipoxygenase-activating protein (FLAP) inhibitor, as an add-on to current therapy on the percentage of neutrophils in induced sputum in asthmatic patients with elevated sputum neutrophils. Approximately 20 subjects will be enrolled onto the study to ensure that approximately 14 evaluable subjects complete the study. All subjects will receive oral placebo and GSK2190915 100mg once daily for up to 16 days. Sputum neutrophilia will be assessed prior to treatment and on treatment. Key assessments: sputum cell counts, biomarker samples in sputum, blood and urine, and pharmacokinetics. Safety will be assessed by vital signs, electrocardiograms (ECGs), clinical laboratory safety tests and collection of adverse events (AEs).~GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5-lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli. As GSK2190915 reproducibly inhibits the production of leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) both in vitro and in vivo it has strong potential utility in the treatment of asthma.
The purpose of this study is to investigate the effect on repeat doses of GSK2190915 in asthmatic patients with a high percentage of neutrophils in their sputum. GSK2190915 will be given as an add on to current therapy, and its effects on the percentage of sputum neutrophils in the patients will be assessed.