A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder.
A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder.
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DOI：
10.1017/s1461145711001027
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发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
Artigas F
中科院分区：
文献类型：
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作者：
Alvarez E;Perez V;Dragheim M;Loft H;Artigas F
使用文拉法辛XR作为DSM-IV-TR重度抑郁症（MDD）患者的活性对照，评价Lu AA 21004与安慰剂相比的疗效、安全性和耐受性。Lu AA 21004是一种新型抗抑郁药，在重组细胞系中是5-HT 3和5-HT 7受体拮抗剂、5-HT 1A受体激动剂、5-HT 1B受体部分激动剂和5-HT转运蛋白抑制剂。在这项为期6周的多中心研究中，429例患者被随机分配（1：1：1：1）至5或10 mg Lu AA 21004、安慰剂或225 mg文拉法辛XR组。所有患者的基线蒙哥马利-卡斯伯格抑郁评定量表（MADRS）总分> 30。主要疗效分析基于MADRS总分，使用分层检验程序调整多重性，从最高剂量与安慰剂开始。Lu AA 21004在第6周MADRS总评分较基线的平均变化方面统计学显著上级优于安慰剂（n=105）（p<0.0001，末次观察值结转），与安慰剂相比的平均治疗差异为5.9（5 mg，n=108）和5.7（10 mg，n=100）分。文拉法辛XR（n=112）在第6周也显著上级安慰剂（p<0.0001）。总共有30名患者因不良事件（AE）而退出研究-安慰剂组：4名（4%）; 5 mg Lu AA 21004组：3名（3%）; 10 mg Lu AA 21004组：7名（7%）;文拉法辛组：16名（14%）。最常见的AE为恶心、头痛、多汗和口干。在临床实验室结果、生命体征、体重或ECG参数中未观察到随时间推移的临床相关变化。在这项研究中，5 mg和10 mg Lu AA 21004治疗6周在MDD患者中有效且耐受性良好。
The efficacy, safety, and tolerability of Lu AA21004 vs. placebo using venlafaxine XR as active reference in patients with DSM-IV-TR major depressive disorder (MDD) were evaluated. Lu AA21004 is a novel antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. In this 6-wk, multi-site study, 429 patients were randomly assigned (1:1:1:1) to 5 or 10 mg Lu AA21004, placebo or 225 mg venlafaxine XR. All patients had a baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total score ⩾30. The primary efficacy analysis was based on the MADRS total score adjusting for multiplicity using a hierarchical testing procedure starting with the highest dose vs. placebo. Lu AA21004 was statistically significantly superior to placebo (n=105) in mean change from baseline in MADRS total score at week 6 (p<0.0001, last observation carried forward), with a mean treatment difference vs. placebo of 5.9 (5 mg, n=108), and 5.7 (10 mg, n=100) points. Venlafaxine XR (n=112) was also significantly superior to placebo at week 6 (p<0.0001). In total, 30 patients withdrew due to adverse events (AEs) – placebo: four (4%); 5 mg Lu AA21004: three (3%); 10 mg Lu AA21004: seven (7%); and venlafaxine: 16 (14%). The most common AEs were nausea, headache, hyperhidrosis, and dry mouth. No clinically relevant changes over time were seen in the clinical laboratory results, vital signs, weight, or ECG parameters. In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD.