Metabolic and Atherosclerosis Research Center, Cincinnati, OH 45212, USA.
Eur Heart J. 2010 Feb;31(4):480-8. doi: 10.1093/eurheartj/ehp601. Epub 2010 Jan 22.
Co-primary objectives were to evaluate dalcetrapib (JTT-705/RO4607381), which targets cholesteryl ester transfer protein (CETP), effects on high-density lipoprotein cholesterol (HDL-C) in participants with coronary heart disease or risk equivalents and to evaluate potential changes in mesenteric lymph nodes.
Double-blind trial with participants randomized (2:1) to dalcetrapib 900 mg/day (higher than 600 mg phase III dose) or placebo, both with atorvastatin, for 24 weeks (n = 135; one without post-baseline efficacy data was excluded from intent-to-treat population); a subset continued for 24-week extension (n = 77). Lipid changes and safety parameters were assessed. Mesenteric lymph nodes were evaluated by magnetic resonance imaging. Dalcetrapib increased HDL-C (33.4%, Week 24; 33.8%, Week 48), decreased CETP activity (-53.5%, Week 24; -56.5%, Week 48), and increased apolipoprotein A-I (11.4%, Week 24; 16.4%, Week 48). Dalcetrapib showed no clinically relevant differences vs. placebo in adverse events, laboratory parameters including aldosterone, electrocardiograms, and vital signs including blood pressure (BP). Dalcetrapib had no measurable, clinically relevant effect on lymph node size.
Dalcetrapib 900 mg administered for up to 48 weeks showed no clinically relevant changes in lymph nodes, BP, or other safety parameters. Dalcetrapib effectively increased HDL-C over 48 weeks of treatment.
主要目的是评估 dalcetrapib（JTT-705/RO4607381），它针对胆固醇酯转移蛋白（CETP），在患有冠心病或风险等同物的参与者中对高密度脂蛋白胆固醇（HDL-C）的影响，并评估肠系膜淋巴结的潜在变化。
双盲试验，参与者随机（2:1）接受 dalcetrapib 900mg/天（高于 III 期 600mg 剂量）或安慰剂，均与阿托伐他汀联合使用，持续 24 周（n=135；一名无基线后疗效数据的患者被排除在意向治疗人群之外）；亚组继续进行 24 周的扩展（n=77）。评估脂质变化和安全性参数。通过磁共振成像评估肠系膜淋巴结。Dalcetrapib 增加了 HDL-C（24 周时为 33.4%，48 周时为 33.8%），降低了 CETP 活性（24 周时为-53.5%，48 周时为-56.5%），并增加了载脂蛋白 A-I（24 周时为 11.4%，48 周时为 16.4%）。与安慰剂相比，Dalcetrapib 在不良反应、包括醛固酮在内的实验室参数、心电图和包括血压（BP）在内的生命体征方面没有显示出临床上有意义的差异。Dalcetrapib 对淋巴结大小没有可测量的、临床上有意义的影响。
在长达 48 周的时间内，给予 900mg/d 的 dalcetrapib 没有在淋巴结、BP 或其他安全性参数方面显示出临床上有意义的变化。Dalcetrapib 在 48 周的治疗期间有效地增加了 HDL-C。
