Bareille Philippe, Hardes Kelly, Donald Alison C
GlaxoSmithKline, Gunnels Wood Road, Stevenage , Hertfordshire , UK .
J Asthma. 2013 Dec;50(10):1077-82. doi: 10.3109/02770903.2013.837480. Epub 2013 Oct 1.
To assess the efficacy of inhaled, repeat doses (28 days) of the glucocorticoid agonist GW870086, which has been designed to inhibit gene transrepression of the glucocorticoid receptor while preserving its transactivation.
This was a randomised, placebo-controlled, two-way crossover study, approved by the independent ethics committees of the study centres. Subjects with FEV(1) 40-85% of the predicted normal value (n = 36) received GW870086 (1 mg, once-daily) and placebo.
No significant change from baseline in forced expiratory volume in one second (FEV(1)) was seen following administration of GW8780086 1 mg relative to placebo; mean FEV(1) (day 28), relative to placebo, was (95% confidence intervals [CI]) -0.077 L (-0.192, 0.038). A moderate positive placebo response was observed on Days 14 and 28: Mean FEV(1) (95% CI) was 0.115 L (0.040, 0.189) and 0.115 L (0.019, 0.212), respectively. The placebo response was more notable in treatment period 1 and was larger than the response to GW870086 1 mg on day 28, irrespective of period. Peak expiratory flow rate results were consistent with FEV(1) and no difference was seen between the GW870086 and placebo for rescue medication usage.
This total lack of effect suggests that repeat-dose GW8700861 mg has suboptimal efficacy in mild to moderate asthma.
评估吸入性重复剂量（28天）糖皮质激素激动剂GW870086的疗效，该药物旨在抑制糖皮质激素受体的基因反式抑制作用，同时保留其反式激活作用。
这是一项随机、安慰剂对照、双向交叉研究，经研究中心独立伦理委员会批准。第一秒用力呼气量（FEV₁）为预测正常值40 - 85%的受试者（n = 36）接受GW870086（1毫克，每日一次）和安慰剂治疗。
与安慰剂相比，给予1毫克GW8780086后，一秒用力呼气量（FEV₁）与基线相比无显著变化；相对于安慰剂，第28天的平均FEV₁（95%置信区间[CI]）为-0.077升（-0.192，0.038）。在第14天和第28天观察到适度的阳性安慰剂反应：平均FEV₁（95% CI）分别为0.115升（0.040，0.189）和0.115升（0.019，0.212）。安慰剂反应在治疗期1更显著，且无论治疗期如何，在第28天均大于对1毫克GW870086的反应。呼气峰值流速结果与FEV₁一致，GW870086与安慰剂在使用缓解药物方面无差异。
完全缺乏效果表明，重复剂量的1毫克GW870086在轻度至中度哮喘中的疗效欠佳。
