哮喘联盟

   摘要
   目的：有两项剂量范围交叉研究，研究1评估长效毒蕈碱拮抗剂芜地溴铵(UMEC)单用治疗未使用吸入糖皮质激素(NCT01641692)的哮喘患者的效果，研究2评估长效毒蕈碱拮抗剂芜地溴铵(UMEC)联合吸入性糖皮质激素糠酸氟替卡松治疗有症状的使用吸入糖皮质激素(NCT01573624)的哮喘患者的效果。该研究的目的是通过测量（第15天）1秒用力呼气容积(FEV1)谷值自基线的改变从而进一步揭示UMEC的剂量-效应关系。
   方法：使用采用了非线性混合效应分析的基于模型的方法评估研究1和2的数据。
   结果：在研究1的剂量范围内，不存在显著的剂量-效应关系。在研究2中，对数-剂量模型的斜率-截距显示出轻微的剂量-效应关系：当FF/UMEC为100/250 mcg时，FEV1增加0.075L的可能性是10%，而有段时间的数据（存在遗留效应）显示FEV1增加0.075L的可能性是88%。
   结论：研究2中的基于模型的方法确定了用于进一步研究的FF/UMEC剂量。
 

（苏欣 审校）
Eur J Clin Pharmacol. 2015 Jul 16. [Epub ahead of print]
 

Dose-response modelling of umeclidinium and fluticasone furoate/umeclidinium inasthma.
 

Yang S1, Goyal N, Beerahee M, Trivedi R, Lee L, Pascoe S.
 

Abstract
PURPOSE:In two dose-ranging crossover studies, the long-acting muscarinic antagonist umeclidinium (UMEC) was assessed as monotherapy in patients with asthma not treated with inhaled corticosteroids (ICS) (NCT01641692 [study 1]) and combined with the ICS fluticasone furoate (FF) in patients with asthmasymptomatic on ICS (NCT01573624 [study 2]). The present study aimed to further characterise the UMEC dose-response relationship with change from baseline trough forced expiratory volume in one second (FEV1) (day 15).
METHODS:A model-based approach using non-linear mixed-effects analyses was used to assess data from studies 1 and 2.
RESULTS:Within the Study 1 dose range, no significant dose-response was demonstrated. In study 2, the slope-intercept on log-dose model showed a mild dose-response, with a 10 % probability of a 0.075-L FEV1improvement with FF/UMEC 100/250 mcg; period 1 data (with an absent carryover effect) indicated an 88 % probability of a 0.075-L FEV1 improvement.
CONCLUSION:The model-based approach in study 2 identified FF/UMEC doses warranting further investigation.

Eur J Clin Pharmacol. 2015 Jul 16. [Epub ahead of print]