Journal Article

Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of SY-004, a Glucokinase Activator, in Healthy Chinese Adults: A Randomized, Phase Ia, Single-Ascending Dose Study

Wang, Yarong, Zhao, Yuqing, Zhuo, Lang, Shao, Feng, Zhang, Hongwen, Wang, Lu, Wang, Libin, Xie, Lijun, Zhou, Sufeng, Liu, Yun, Ou, Ning, Chen, Juan

2022

Overview

SY-004, a dual-acting full glucokinase activator, is under development to provide a dose-dependent improvement of glucose control. This study aimed to assess the tolerability, safety, and pharmacokinetic and pharmacodynamic properties of SY-004 in healthy Chinese adults. Two study participants were administered 2 mg of SY-004 in the 2-mg cohort, whereas 6 study participants were randomized with 4 study participants receiving SY-004 and 2 receiving placebo in the 20-mg cohort. In each of other 3 dose cohorts (40, 80, and 120 mg), 12 participants were randomized in a 10:2 ratio to receive single oral SY-004 capsules or placebos. Drug concentrations, glucose and insulin levels, and safety data were assessed and analyzed. Noncompartmental analysis was used to determine SY-004 pharmacokinetic parameters. SY-004 was generally well tolerated. Nine of the 44 study participants reported 17 treatment-related adverse events, and most treatment-related adverse events were mild. SY-004 had approximately dose-proportional increases in systemic exposure. The mean t½ ranged from 37.6 to 49.9 hours, and CL/F values ranged from 67.1 to 110 L/h across all doses. The cumulative amounts of the unchanged drug excreted in urine were very low, accounting for no more than 1.53% of the given doses. No significant difference in sex was observed in pharmacokinetic parameters. The pharmacodynamic response appeared to slightly correlate with dose. SY-004, a new potential glucokinase activator, had favorable safety profiles and good PK characteristics. The glucose-lowering effects were slightly dose related. The SY-004 data in healthy Chinese adults supports further development. ClinicalTrials.gov identifier: NCT03171623.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Adult / Adverse events / Area Under Curve / China / Chinese / Diabetes / Dose-Response Relationship, Drug / Double-Blind Method / Drug dosages / Enzymes / FDA approval / Glucokinase / Glucokinase - metabolism / glucokinase activator / Glucose / Healthy Volunteers / Humans / Hyperglycemia / Hypoglycemia / Insulin / Insulin resistance / Internal Medicine / Medical laboratories / Metabolism / Metabolites / Pharmaceutical industry / Pharmacodynamics / Pharmacokinetics / Placebos / Plasma / Safety / SY-004 / tolerability / Urine / Vital signs