A Multi-center 12-week Study of HMS5552 in T2DM

A Multi-center, Randomized, Double-blind, Placebo-controlled, 12-week Phase II Study to Evaluate the Safety, Tolerability, Efficacy and Population PK of HMS5552 in Type 2 Diabetic Adult Subjects

This study evaluates the safety, tolerability, efficacy and population PK of HMS5552 in type 2 diabetic adult subjects,there will be 5 groups ,4 groups will receive HMS5552,while 1 will receive placebo.

Glucokinase (GK, also called hexokinase IV or D) can phosphosphorylate glucose to glucose-6-phosphate (G-6-P) in pancreatic β-cells and liver cells, which represents the first step of glucose metabolism. GK also acts as a glucose sensor and exerts a key role in maintaining glucose homeostasis. HMS5552 is a 4th-generation GK agonist or activator (GKA), which was originally licensed from Roche and subsequently developed by Hua Medicine. HMS5552 has been shown to activate GK in pancreatic beta cells, liver and intestinal epithelial cells. It regulates systemic blood glucose through a variety of mechanisms including directly enhancing insulin release (pancreas), inhibiting production of endogenous glucose (liver) and by indirectly promoting GLP-1 release (enteroendocrine L-cells).

Inclusion Criteria:

1. Male & female, 40~75 years old
2. T2DM patients，anti-hyperglycemic drug-naïve and on diet & exercise for at least 3 months, or with glucose controlled by Metformin or α-glucosidase inhibitor alone
3. HbA1c 7.5~10.5% at screening and pre-randomization
4. Fasting plasma glucose (FPG)7.0~11.1 millimole/liter (mmol/L, local lab) at screening, and 7.0~13.3 millimole/liter (mmol/L, central lab) at pre-randomization
5. BMI: 19~30kg/m^2 & TG<5.5mmol/L

Exclusion Criteria:

1. T1D，secondary DM, pre-DM
2. kidney diseases or eGFR MDRD<60ml/min/1.73m^2
3. unstable CVDs
4. liver diseases
5. mental or CNS diseases