Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Drug Des Devel Ther. 2022 Sep 6;16:2967-2980. doi: 10.2147/DDDT.S372575. eCollection 2022.
Sotagliflozin (LX4211) is a dual inhibitor of sodium-glucose cotransporter (SGLT)1 and SGLT2 being investigated to improve glycemic control in adults with diabetes. This study was firstly conducted to assess the pharmacokinetic (PK), pharmacodynamic (PD) profiles, safety and tolerability in Chinese healthy subjects after administration of sotagliflozin.
This was a Phase I, randomized, double-blind, placebo-controlled, ascending multiple-dose study. Healthy subjects received 200mg or 400mg of sotagliflozin or placebo once daily for 8 days, respectively. PK parameters of sotagliflozin and LX4211-GLU (main metabolite), as measured by blood samples collected pre/postdose on Day 1/predose on Day 2-Day 8/postdose on Day 8, and PD parameters of absolute urinary glucose excretion (UGE) were determined. Treatment-emergent adverse events (TEAEs) were evaluated.
Overall, 24 subjects were enrolled and randomized to sotagliflozin 200 mg (N = 9), sotagliflozin 400 mg (N = 9), or placebo (N = 6) group, and all subjects completed the study. Sotagliflozin was rapidly absorbed with dose-proportional systemic exposure and a moderate degree (less than 2-fold) of accumulation. Sotagliflozin plasma concentrations peaked at 1.0 h post dose. On Day 8, the estimated increases for C and AUC were 1.89-fold and 1.70-fold. The pooled accumulation ratio of sotagliflozin was 1.57 for C and 1.84 for AUC. LX4211-GLU had similar PK features. UGE was significantly elevated in both sotagliflozin groups relative to the placebo group. All TEAEs were mild and resolved without sequelae. There were no serious AEs or other significant TEAEs.
Sotagliflozin was rapidly absorbed with dose-proportional systemic exposure and a moderate degree of accumulation. Both 200 mg and 400 mg sotagliflozin per day were well tolerated in Chinese healthy subjects.
索格列净（LX4211）是一种钠-葡萄糖共转运蛋白（SGLT）1和 SGLT2 的双重抑制剂，正在研究用于改善糖尿病成人的血糖控制。本研究首次评估了索格列净在中国健康受试者中的药代动力学（PK）、药效学（PD）特征、安全性和耐受性。
这是一项 I 期、随机、双盲、安慰剂对照、递增剂量的研究。健康受试者分别接受 200mg 或 400mg 索格列净或安慰剂，每日一次，连续 8 天。通过第 1 天给药前/后和第 2-8 天给药前/第 8 天给药后采集的血样，测定索格列净和 LX4211-GLU（主要代谢物）的 PK 参数（以血药浓度-时间曲线下面积[AUC]和峰浓度[C]表示），并测定绝对尿葡萄糖排泄（UGE）的 PD 参数。评估治疗中出现的不良事件（TEAE）。
共有 24 名受试者入组并随机分为索格列净 200mg 组（N=9）、索格列净 400mg 组（N=9）或安慰剂组（N=6），所有受试者均完成了研究。索格列净吸收迅速，呈剂量比例的全身暴露，蓄积程度适中（<2 倍）。索格列净血浆浓度在给药后 1.0 小时达到峰值。第 8 天，C 和 AUC 的估计增加分别为 1.89 倍和 1.70 倍。索格列净的累积比为 C 为 1.57，AUC 为 1.84。LX4211-GLU 具有相似的 PK 特征。与安慰剂组相比，索格列净组的 UGE 均显著升高。所有 TEAEs 均为轻度，无后遗症。无严重不良事件或其他重要的 TEAEs。
索格列净吸收迅速，呈剂量比例的全身暴露，蓄积程度适中。每天 200mg 和 400mg 索格列净在中国健康受试者中均耐受良好。
