Phase I Clinical Trial Unit, First Hospital, Jilin University, Changchun, China.
Department of pharmacy, Maternal and Child Health and Family Planning Service Center of Changchun, Changchun, China.
Expert Opin Investig Drugs. 2021 Dec;30(12):1241-1248. doi: 10.1080/13543784.2021.2008906. Epub 2021 Nov 29.
Glucagon-like peptide-1 (GLP-1) mimetics are widely used for treating type 2 diabetes (T2D) with pleiotropic effects on heart and kidneys. The safety/tolerability and pharmacokinetics/pharmacodynamics ((PK/PD) of CJC-1134-PC (a long-acting GLP-1) were investigated in Chinese.
Two randomized, double-blind, placebo-controlled phase I studies were conducted. Study A: 30 healthy subjects received (subcutaneously injected) a single dose (2 mg) or titrate doses (2 + 3 and 2 + 3 + 4 mg at weekly intervals) of CJC-1134-PC. Study B: 49 T2D subjects received 10 weekly doses (1, 2, 3, and 4 mg).
CJC-1134-PC was well tolerated with gastrointestinal (GI) side effects. Higher doses increased the adverse events risk. CJC-1134-PC was steadily absorbed, with maximum plasma concentrations(C) occurring at 36-72 h and 48 h after administration in healthy and T2D subjects, respectively. The steady-state exposures in T2D subjects increased more than the dose-proportionality(1-3 mg). The mean t ranged from 111.6 to 127.6 h. After four- five weeks of targeting doses, steady state was reached in T2D subjects with apparent accumulation effect. At week 11 for T2D subjects, HbA1c mean baseline change was significantly different than that of the placebo, and the fasting plasma glucose (FPG) was not significantly altered.
The safety and PK/PD profiles of weekly CJC-1134-PC doses support Phase II studies with guidance on optimal-dose selection. Clinical trial registration: ChiCTR-IPC-15007190.
胰高血糖素样肽-1 (GLP-1) 类似物广泛用于治疗 2 型糖尿病 (T2D)，对心脏和肾脏具有多种作用。在中国，对 CJC-1134-PC（一种长效 GLP-1）的安全性/耐受性和药代动力学/药效学 (PK/PD) 进行了研究。
进行了两项随机、双盲、安慰剂对照的 I 期研究。研究 A：30 名健康受试者接受（皮下注射）单剂量（2 毫克）或滴定剂量（2+3 和 2+3+4 毫克，每周间隔）CJC-1134-PC。研究 B：49 名 T2D 患者接受 10 周剂量（1、2、3 和 4 毫克）。
CJC-1134-PC 耐受性良好，有胃肠道 (GI) 副作用。较高剂量增加了不良事件的风险。CJC-1134-PC 吸收稳定，健康受试者和 T2D 受试者分别在给药后 36-72 小时和 48 小时达到最大血浆浓度 (C)。T2D 受试者的稳态暴露量超过剂量比例性 (1-3 毫克)。平均 t 范围为 111.6 至 127.6 小时。在 T2D 患者中，经过四周至五周的靶向剂量治疗，达到稳态，并出现明显的蓄积效应。在 T2D 患者第 11 周，HbA1c 平均基线变化与安慰剂明显不同，空腹血糖 (FPG) 没有明显改变。
每周 CJC-1134-PC 剂量的安全性和 PK/PD 特征支持 II 期研究，为最佳剂量选择提供了指导。临床试验注册：ChiCTR-IPC-15007190。
