Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Clin Ther. 2013 Jan;35(1):77-86. doi: 10.1016/j.clinthera.2012.11.009. Epub 2012 Dec 28.
A manufacturer of atorvastatin is seeking marketing approval in Korea of a generic product for adult patients with primary hypercholesterolemia.
The objective of this study was to compare the efficacy and tolerability of a new generic formulation of atorvastatin (test) with those of an original formulation of atorvastatin (reference) to satisfy regulatory requirements for marketing of the generic product in Korea.
Patients enrolled were aged 20 to 79 years with documented primary hypercholesterolemia who did not respond adequately to therapeutic lifestyle changes and with a LDL-C level >100 mg/dL from a high-risk group of coronary artery disease patients. Eligible patients were randomized to receive 1 of the 2 formulations of atorvastatin 20 mg per day for 8 weeks. The primary end point was the percent change in LDL-C level from baseline to week 8. Secondary end points included the percent change in total cholesterol, triglycerides, HDL-C level, apolipoprotein B:apolipoprotein A-I ratio, LDL:HDL ratio, LDL-C particle size, high-sensitivity C-reactive protein from baseline to week 8, and achievement rate of the LDL-C goal.
A total of 298 patients (141 men and 157 women; 149 patients in each group; mean [SD] age, 62.4 [9.2] in the test group vs 60.3 [8.9] years in the reference group) were included. LDL-C levels were significantly decreased from baseline to week 8 in both groups, and there was no significant difference in the percent change in LDL-C level between groups (-44.0% [17.2%] in the test group, -45.4% [16.9%] in the reference group; P = 0.49). The between-group differences in the percent changes in total cholesterol and triglyceride levels were not statistically significant. In addition, there was no significant difference between the 2 groups in percent changes in HDL-C, apolipoprotein B:apolipoprotein A-I ratio, LDL-C:HDL-C ratio, LDL-C particle size, high-sensitivity C-reactive protein, and the achievement rate of the LDL-C goal. Two (1.3%) patients in the reference group (N = 150) experienced treatment-related serious adverse events (AEs): toxic hepatitis and aggravation of chest pain. Common AEs were cough (4.1%), myalgia (2.1%), and indigestion (1.4%) in the test formulation group and cough (5.3%), creatine kinase elevation (2.7%), and edema (0.7%) in the reference formulation group; however, the differences in overall prevalence of AEs between the 2 treatment groups was not significant (P = 0.88).
There were no significant differences observed in the efficacy and tolerability between the test and reference formulations of atorvastatin in these Korean adult patients with primary hypercholesterolemia.
阿托伐他汀的制造商正在寻求在韩国为患有原发性高胆固醇血症的成年患者批准一种仿制药。
本研究旨在比较阿托伐他汀新仿制药（试验）与阿托伐他汀原研药（参照）的疗效和耐受性，以满足该仿制药在韩国上市的监管要求。
入组患者年龄为 20 至 79 岁，确诊为原发性高胆固醇血症，经生活方式治疗后未得到充分缓解，且高危冠心病患者的 LDL-C 水平＞100mg/dL。合格患者被随机分配至每天接受 1 种阿托伐他汀 20mg 的 2 种制剂治疗 8 周。主要终点是第 8 周时 LDL-C 水平从基线的变化百分比。次要终点包括总胆固醇、甘油三酯、HDL-C 水平、载脂蛋白 B:载脂蛋白 A-I 比值、LDL:HDL 比值、LDL-C 颗粒大小、第 8 周时高敏 C 反应蛋白和 LDL-C 目标达标率的变化百分比。
共有 298 例患者（男性 141 例，女性 157 例；试验组 149 例，参照组 149 例；平均[标准差]年龄分别为试验组 62.4[9.2]岁，参照组 60.3[8.9]岁）纳入研究。两组患者的 LDL-C 水平均较基线显著降低，组间 LDL-C 水平的变化百分比无显著差异（试验组为-44.0%[17.2%]，参照组为-45.4%[16.9%]；P=0.49）。两组间总胆固醇和甘油三酯水平的变化百分比差异无统计学意义。此外，两组间 HDL-C、载脂蛋白 B:载脂蛋白 A-I 比值、LDL:HDL 比值、LDL-C 颗粒大小、高敏 C 反应蛋白和 LDL-C 目标达标率的变化百分比均无显著差异。参照组（n=150）有 2 例（1.3%）患者发生与治疗相关的严重不良事件（AE）：药物性肝炎和胸痛加重。试验组常见 AE 为咳嗽（4.1%）、肌痛（2.1%）和消化不良（1.4%），参照组为咳嗽（5.3%）、肌酸激酶升高（2.7%）和水肿（0.7%）；然而，两组间总体 AE 发生率差异无统计学意义（P=0.88）。
在这些韩国原发性高胆固醇血症成年患者中，阿托伐他汀仿制药与原研药在疗效和耐受性方面无显著差异。
