The effect of GSK2190915, a 5-lipoxygenase‐activating protein inhibitor, on exercise-induced bronchoconstriction
Exercise-induced bronchoconstriction (EIB) describes the condition whereby exercise causes airflow obstruction that lasts for up to 90 minutes without treatment. This double-blind, placebo-controlled, five-way crossover study investigated the dose response and duration of action of
a 5-lipoxygenase‐activating protein inhibitor, GSK2190915, to inhibit EIB in subjects with asthma. Forty-seven subjects with EIB were enrolled. Exercise challenge testing was scheduled at 2, 9.5, and 24 hours after receiving a single dose of GSK2190915 (10, 50, 100, and 200 mg) or placebo
in randomized order. GSK2190915 at 200 and 100 mg significantly attenuated the response to exercise at 2 and 9.5 hours postdose, respectively, compared with placebo. The adjusted mean maximum percentage change from baseline forced expiratory volume at 1 second within 60 minutes postexercise
challenge (FEV1 (0‐60)) treatment difference for GSK2190915 at 200 mg compared with placebo at 2 hours postdose was 6.30% (95% CI, 3.06, 9.54), corresponding to a 40% attenuation of the placebo response to exercise; the treatment difference between GSK2190915 at 100 mg and
placebo at 9.5 hours postdose was 3.49% (95% CI, 1.02, 5.95), corresponding to a 41% attenuation of the placebo response to exercise. No significant effect was seen at 24 hours postdose with any dose; however, investigation of statistically significant treatment-related effects at this time
point was limited because of the small fall in adjusted mean FEV1 (0‐60) (−7.61%; 95% CI, −10.23, −4.99) after placebo. GSK2190915 may be of benefit in EIB prevention. GSK Clinical Study LPA112025; ClinicalTrials.gov identifier number: NCT00812929.
Keywords: 5-lipoxygenase activating protein; Asthma; FLAP inhibitor; GSK2190915; cysteinyl leukotrienes; exercise challenge testing; exercise model; exercise-induced asthma; exercise-induced bronchoconstriction; leukotriene antagonist
Document Type: Research Article
Affiliations: GlaxoSmithKline, London, UK
Publication date: 01 March 2014
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