Zafgen, Inc., Cambridge, MA, USA.
Obesity (Silver Spring). 2013 Sep;21(9):1782-8. doi: 10.1002/oby.20356. Epub 2013 May 25.
Evaluate the safety and tolerability of beloranib, a fumagillin-class methionine aminopetidase-2 (MetAP2) inhibitor, in obese women over 4 weeks.
Thirty-one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).
The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was -3.8 kg (95% CI -5.1, -0.9; N = 8) versus -0.6 kg with placebo (-4.5, -0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL-cholesterol, as well as improvement in C-reactive protein and reduced sense of hunger. Changes in β-hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor-21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.
Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C-reactive protein, and adiponectin.
评估贝洛拉尼布（一种新型烟曲霉素类甲硫氨酸氨肽酶-2（MetAP2）抑制剂）在肥胖女性中的安全性和耐受性，疗程为 4 周。
31 名肥胖女性（平均 BMI 为 38kg/m2）被随机分为静脉 0.1、0.3 或 0.9mg/m2 贝洛拉尼布或安慰剂，每周 2 次，共 4 周（每组 N = 7、6、9 和 9）。
最常见的不良反应为头痛、输注部位损伤、恶心和腹泻。与安慰剂相比，贝洛拉尼布更易引起恶心和输注部位损伤。最常见的停药原因是静脉通路丧失。无临床意义的实验室检查异常。在完成 4 周疗程的受试者中，与安慰剂（-0.6kg，95%CI -4.5，-0.1；N=6）相比，0.9mg/m2 贝洛拉尼布组的中位体重减轻量为-3.8kg（95%CI -5.1，-0.9；N=8）。0.1 和 0.3mg/m2 贝洛拉尼布的体重变化与安慰剂相似。贝洛拉尼布（0.9mg/m2）可使甘油三酯和 LDL 胆固醇分别显著降低 42%和 18%，并改善 C 反应蛋白和降低饥饿感。β-羟基丁酸、脂联素、瘦素和成纤维细胞生长因子-21 的变化与 MetAP2 抑制的假定机制一致。血糖和血压保持不变。
贝洛拉尼布治疗耐受性良好，与快速减肥以及改善血脂、C 反应蛋白和脂联素有关。
