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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: HMS5552
* Drug: HMS5552
* Drug: HMS5552
* Drug: HMS5552
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male & female, 40 75 years old 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 HbA1c 7.5 10.5% at screening and pre-randomization 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 BMI: 19 30kg/m^2 & TG<5.5mmol/L Exclusion Criteria: T1D，secondary DM, pre-DM kidney diseases or eGFR MDRD<60ml/min/1.73m^2 unstable CVDs liver diseases mental or CNS diseases

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HMS5552 dose 1<br>75mgQD oral administration | Drug: HMS5552<br>* 75mgQD<br>* Other names: GKA;|
| Experimental: HMS5552 dose 2<br>100mgQD oral administration | Drug: HMS5552<br>* 100mgQD<br>* Other names: GKA;|
| Experimental: HMS5552 dose 3<br>50mgBID oral administration | Drug: HMS5552<br>* 50mgBID<br>* Other names: GKA;|
| Experimental: HMS5552 dose 4<br>75mgBID oral administration | Drug: HMS5552<br>* 75mgBID<br>* Other names: GKA;|
| Placebo Comparator: Placebo<br>Placebo, BID/QD oral administration | Other: Placebo<br>* QD/BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| After 12-week Treatment, the Change From Baseline in HbA1c | Assess the percentage of Hemoglobin A1c (HbA1c) changes at week 12. In the group HMS5552 dose3, a subject without follow-up data for HbA1c available was excluded. And in the group HMS5552 dose4, two subjects without follow-up data for HbA1c available were excluded. So the overall number of baseline participants is not consistent with numbers provided in any of the rows in the participant flow module. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2hPPG | Using a standard meal tolerance test, to assess 2-h postprandial glucose (2hPPG). In this test, subjects were received meals standardised by China National Cereals, which supplied by Oils and Foodstuffs Corporation and contained 353 kcal, 75 g carbohydrate, 1.48 g fat, and 8.0 g protein. Collect the blood samples to detect blood glucose 2 hours after starting the meal. | Baseline and 12 weeks | 
| Change From Baseline in FPG |  | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GKA,T2DM,HMS5552