Abstract:
AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George\'s Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.
摘要:
AVANT是第3阶段,24周,随机化,平行组,双盲,双假人,安慰剂对照研究评估阿地铵/福莫特罗400μg/12μg组合与单药治疗和阿地铵与安慰剂(1:1:1:1)的疗效和安全性亚洲患者(~70%为中国人)患有中度至重度稳定期慢性阻塞性肺疾病.对终点进行分层分析,以纳入I型错误控制。在第24周,阿地铵/福莫特罗在1秒内给药后1小时的用力呼气量(FEV1)与阿地铵(最小二乘[LS]平均92mL;95%置信区间[CI]60,124mL;p<0.001),在FEV1与福莫特罗之间(LS平均85mL;95%CI53,117mL;p<0.001)。此外,与安慰剂相比,阿地铵改善了FEV1的低谷(LS均值134mL;95%CI103,166mL;p<0.001)。在第24周,阿地铵/福莫特罗与安慰剂组的过渡性呼吸困难指数局灶性评分有所改善(LS平均0.8;95%CI0.2,1.3;p=0.005),但阿地铵与安慰剂组没有改善(LS平均0.4;95%CI-0.1,1.0;p=0.132)。阿地溴铵/福莫特罗与安慰剂(LS均值-4.0;95%CI-6.7-1.4;p=0.003)和阿地溴铵与安慰剂(LS均值-2.9;95%CI-5.5,-0.3;p=0.031)的圣乔治呼吸问卷总分有所改善。阿地铵/福莫特罗和阿地铵耐受性良好,安全性发现与已知概况一致;治疗引起的不良事件(AE)发生率(阿地铵/福莫特罗:54.8%;阿地铵:47.4%;安慰剂:53.9%),严重不良事件(7.2、7.9和7.8%,分别),以及导致研究药物停止的不良事件(2.3、1.5和2.2%,分别)组间相似。