Division of Nephrology, Department of Medicine, Showa University School of Medicine, Namics 301, 4-24-51 Takanawa, Minato-ku, Tokyo, 108-0074, Japan.
R&D Division, Kyowa Hakko Kirin Co. Ltd., 1-9-2 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
Clin Drug Investig. 2018 Oct;38(10):945-954. doi: 10.1007/s40261-018-0687-4.
Evocalcet is a novel calcimimetic agent with potential to improve the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. This study aimed to determine the pharmacokinetics, pharmacodynamics, and safety of evocalcet in healthy Japanese subjects.
This was a single-blind, placebo-controlled, single-dose study and an 8-day multiple-dose study of evocalcet (MT-4580/KHK7580) in 66 healthy Japanese subjects.
After a single dose of evocalcet 1-20 mg, the time to maximum plasma concentration was attained in 1.5-2 h (median), and the elimination half-life was 12.98-19.77 h (mean). Within this dose range, the maximum plasma concentration and area under plasma concentration-time curve increased dose proportionally, confirming linearity. The trough plasma concentrations were relatively unchanged after multiple administration of evocalcet 6 and 12 mg. Evocalcet decreased intact parathyroid hormone and corrected calcium and phosphorus levels in a dose-proportional manner. Regarding its safety, no upper gastrointestinal adverse event occurred after the single and multiple administration of evocalcet at doses up to 12 mg. Tetany was detected in 1 subject (17%) after multiple administration of evocalcet 12 mg. In healthy subjects, the tolerability and safety of evocalcet were observed for a single dose of evocalcet at doses up to 20 mg, and for multiple doses up to 12 mg.
These results suggest that evocalcet may have a comparable efficacy and better safety profile than that of cinacalcet, one of the current treatments for secondary hyperparathyroidism in patients with chronic kidney disease.
依卡路特是一种新型的拟钙剂，有望改善慢性肾脏病患者继发性甲状旁腺功能亢进症的治疗效果。本研究旨在评估依卡路特在日本健康受试者中的药代动力学、药效学和安全性。
这是一项单盲、安慰剂对照、单次和 8 天多次给予依卡路特（MT-4580/KHK7580）的研究，共纳入 66 例日本健康受试者。
单次给予依卡路特 1-20mg 后，最大血浆浓度的时间在 1.5-2h（中位数）达到，消除半衰期为 12.98-19.77h（均值）。在该剂量范围内，最大血浆浓度和血浆浓度-时间曲线下面积呈剂量依赖性增加，表明具有线性特征。多次给予 6mg 和 12mg 依卡路特后，谷浓度保持相对稳定。依卡路特以剂量依赖性方式降低全段甲状旁腺激素和校正钙磷水平。关于安全性，单次和多次给予依卡路特剂量达 12mg 时，未发生上消化道不良事件。12mg 多次给药后，1 例（17%）受试者出现抽搐。在健康受试者中，单次给予依卡路特剂量达 20mg 和多次给予剂量达 12mg 时，依卡路特具有良好的耐受性和安全性。
这些结果表明，依卡路特可能具有与西那卡塞相当的疗效和更好的安全性，西那卡塞是目前治疗慢性肾脏病患者继发性甲状旁腺功能亢进症的一种药物。
