A Prospective, Multicentre, Open-Label Single-Arm Exploratory Study to Evaluate Efficacy and Safety of Saroglitazar on Hypertriglyceridemia in HIV Associated Lipodystrophy

Objective
This study was designed to explore the efficacy and safety of saroglitazar 4 mg on hypertriglyceridemia in patients with HIV associated lipodystrophy.
Methods
During this 12-week prospective, multi-centric, open-label, single arm exploratory study, 50 patients were enrolled to receive saroglitazar 4 mg orally once daily in the morning before breakfast. The primary efficacy endpoint was the percent change in triglyceride (TG) levels from baseline to Week 6 and Week 12. The secondary efficacy endpoints were assessment of low-density-lipoprotein (LDL), very-low-density-lipoprotein (VLDL), high-density-lipoprotein (HDL), non-HDL cholesterol, total cholesterol, apo-lipoprotein (Apo) A1, Apo B, and C-peptide and fasting insulin for HOMA beta and HOMA IR. Safety assessment was performed during the study.
Results
Saroglitazar 4 mg significantly decreased the serum TG levels from baseline at Week 6 (percent change: -40.98; 95% CI: -50.82, -31.15) and Week 12 (percent change -45.11; 95% CI: -52.37, -37.86). Reduction in VLDL cholesterol (percent change: -46.33; 95% CI: -52.89, -39.76) and total cholesterol (percent change: 7.37; 95% CI: 1.96, 12.78) was observed at week 12 from baseline. Saroglitazar increased HDL cholesterol (percent change: 34.56, 95% CI: 22.22, 46.90), Apo A1 (percent change: 33.16; 95% CI: 18.69, 47.63) and Apo B (percent change: 10.55, 95% CI: 2.86, 18.25) levels at week 12 from baseline. Saroglitazar treatment led to increase in the C-peptide (percent change: 59.42, 95% CI: 48.78, 70.06), fasting insulin levels (percent change: 47.10; 95% CI: 38.63, 55.57), HOMA of beta cell function for C-peptide (percent change: 71.67; 95% CI: 39.09, 104.26) and HOMA of insulin resistance for C-peptide (percent change: 58.29, 95% CI: 46.74, 69.83) at week 12 from baseline. Saroglitazar treatment was safe and well tolerated in this study.
Conclusion
Overall, the observed changes in lipid profile after 12 weeks of saroglitazar treatment were in the direction of improvement in patients with HIV associated lipodystrophy.
Trial Registration
Clinical Trial Registry of India Phase II/CTRI/2010/091/000107

研究目的
本研究旨在探讨萨拉格列扎（saroglitazar）4 mg治疗HIV相关脂肪营养不良患者高甘油三酯血症的有效性与安全性。

研究方法
本项为期12周的前瞻性、多中心、开放标签、单臂探索性研究共纳入50例患者，予萨拉格列扎（saroglitazar）4 mg每日晨起早餐前口服一次。主要疗效终点为基线至第6周、第12周时甘油三酯（triglyceride, TG）水平的百分比变化。次要疗效终点包括低密度脂蛋白（low-density-lipoprotein, LDL）、极低密度脂蛋白（very-low-density-lipoprotein, VLDL）、高密度脂蛋白（high-density-lipoprotein, HDL）、非HDL胆固醇、总胆固醇、载脂蛋白（apo-lipoprotein, Apo）A1、Apo B，以及用于评估HOMAβ细胞功能与HOMA胰岛素抵抗的C肽与空腹胰岛素水平。研究期间同步开展安全性评估。

研究结果
萨拉格列扎4 mg可显著降低患者血清TG水平：第6周时较基线变化百分比为-40.98%（95%置信区间：-50.82%，-31.15%），第12周时为-45.11%（95%置信区间：-52.37%，-37.86%）。至第12周时，患者VLDL胆固醇水平较基线降低46.33%（95%置信区间：-52.89%，-39.76%），总胆固醇水平较基线升高7.37%（95%置信区间：1.96%，12.78%）；HDL胆固醇水平较基线升高34.56%（95%置信区间：22.22%，46.90%），Apo A1升高33.16%（95%置信区间：18.69%，47.63%），Apo B升高10.55%（95%置信区间：2.86%，18.25%）。同时，第12周时患者C肽水平较基线升高59.42%（95%置信区间：48.78%，70.06%），空腹胰岛素水平升高47.10%（95%置信区间：38.63%，55.57%）；基于C肽的HOMAβ细胞功能指数升高71.67%（95%置信区间：39.09%，104.26%），HOMA胰岛素抵抗指数升高58.29%（95%置信区间：46.74%，69.83%）。本研究中，萨拉格列扎治疗安全性良好，患者耐受性佳。

研究结论
总体而言，经12周萨拉格列扎治疗后，HIV相关脂肪营养不良患者的血脂谱所出现的变化均指向临床改善。

试验注册
印度临床试验注册中心II期/CTRI/2010/091/000107