title: The 5-lipoxygenase-activating protein inhibitor, GSK2190915, attenuates the early and late responses to inhaled allergen in mild asthma.
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.
  
  
  CONCLUSIONS
  GSK2190915 shows potential as a treatment for patients with asthma.
authors: GlaxoSmithKline, London, United Kingdom.
authors: S E
authors: SE
authors: Kent
authors: M
authors: M
authors: Boyce
authors: Z
authors: Z
authors: Diamant
authors: D
authors: D
authors: Singh
authors: B J
authors: BJ
authors: O'Connor
authors: P S
authors: PS
authors: Saggu
authors: V
authors: V
authors: Norris
mesh_terms: D058946:5-Lipoxygenase-Activating Protein Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001985:Bronchial Provocation Tests; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000097:blood / Q000652:urine; D008297:Male; D010421:Pentanoic Acids / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use*; D012129:Respiratory Function Tests; D013183:Sputum / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C552410:3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid; D058946:5-Lipoxygenase-Activating Protein Inhibitors; D000485:Allergens; D007211:Indoles; D010421:Pentanoic Acids; D007975:Leukotriene B4