Efficacy, safety and tolerability of GSK2190915, a 5-lipoxygenase activating protein inhibitor, in adults and adolescents with persistent asthma: a randomised dose-ranging study

摘要: GSK2190915 is a high affinity 5-lipoxygenase-activating protein inhibitor being developed for the treatment of asthma. The objective this study was to evaluate efficacy, dose–response and safety in subjects with persistent asthma treated short-acting beta2-agonists (SABAs) only. Eight-week multicentre, randomised, double-blind, double-dummy, stratified (by age smoking status), parallel-group, placebo-controlled aged ≥12 years forced expiratory volume 1 second (FEV1) 50–85% predicted. Subjects (n = 700) were randomised receive once-daily (QD) oral (10–300 mg), twice-daily inhaled fluticasone propionate 100 μg, montelukast 10 mg QD or placebo. primary endpoint mean change from baseline (randomisation) trough (morning pre-dose pre-rescue bronchodilator) FEV1 at end 8-week period. Secondary endpoints included morning evening peak flow, symptom-free days nights, rescue-free day night-time symptom scores, rescue medication use, withdrawals due lack Asthma Control Questionnaire Quality Life scores. For endpoint, there no statistically significant difference between any dose However, repeated measures sensitivity analysis demonstrated nominal statistical significance 30 mg compared placebo (mean difference: 0.115 L [95% confidence interval: 0.00, 0.23], p = 0.044); nominally differences observed other doses. secondary endpoints, decreases day-time scores SABA use versus (p ≤ 0.05). No relationship across range studied; appeared be sub-optimal. associated dose-dependent reduction urinary leukotriene E4. profile incidence adverse events similar groups. Efficacy use. additional improvement on efficacy gained by administration doses greater than 30 mg. well-tolerated. These results may support further studies Clinicaltrials.gov: NCT01147744 .