Objectives: Janagliflozin (JGZ) is a novel sodium-glucose cotransporter 2 (SGLT2) inhibitor in development for the treatment of type 2 diabetes mellitus (T2DM). This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of JGZ in Chinese patients with T2DM.
Methods: In this double-blind, parallel-controlled study, 36 patients with inadequately controlled T2DM were randomized into JGZ 25 mg, JGZ 50 mg, dapagliflozin 10 mg, or placebo cohort in a 1:1:1:1 ratio. Patients were treated with a single dose on Day 1, and then once daily from Day 4 to Day 17.
Results: JGZ was readily absorbed with Cmax observed at 2.00 hours (median). The half-life was estimated to be 21.2-23.3 hours at steady state. Plasma JGZ exposure increased in a dose-proportional manner and the accumulation rates were relatively low in Cmax (1.46-1.49) and AUC0-24 (1.67-1.81). Mean (SD) changes from baseline in 24 hour urinary glucose excretion (UGE) were 72.8 (26.2), 78.7 (17.3), 85.8 (25.2), and 2.20 (7.22) g after single dose, and were 92.4 (25.4), 94.2 (29.1), 87.6 (32.2), and 6.26 (24.3) g after multiple doses with JGZ 25 mg, JGZ 50 mg, dapagliflozin 10 mg, and placebo, respectively. Mean (SD) changes from baseline in fasting plasma glucose on Day 17 were 2.18 (1.62), 2.66 (2.01), 2.79 (1.44), and 1.70 (2.04) mmol/L for the four groups, respectively. Mean (SD) changes from baseline in A1C on Day 18 were 0.45% (0.29%), 0.33% (0.57%), 0.62% (0.35%), and 0.07% (0.80%) for the four groups, respectively. Adverse events were mostly mild or moderate with no hypoglycemia episode, serious adverse event, or discontinuation due to adverse event.
Conclusions: JGZ exhibited favorable pharmacokinetics profiles in Chinese patients with T2DM and was well tolerated. JGZ treatments resulted in increase in UGE and improvement in glycemic control. JGZ 25 mg and 50 mg are recommended for further clinical studies.
Y. Ding: None.
XuanZhu Pharma Co., Ltd.