Clinical trial NCT02561338: A Multi-center 12-week Study of HMS5552 in T2DM
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: GKA,T2DM,HMS5552
Lead sponsor: Hua Medicine Limited
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2015-09-28
Enrollment: 258
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: After 12-week Treatment, the Change From Baseline in HbA1c
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change From Baseline in 2hPPG
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in FPG
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
affiliation: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: Dalong Zhu, MD，PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhu D, Gan S, Liu Y, Ma J, Dong X, Song W, Zeng J, Wang G, Zhao W, Zhang Q, Li Y, Fang H, Lv X, Shi Y, Tian H, Ji L, Gao X, Zhang L, Bao Y, Lei M, Li L, Zeng L, Li X, Hou X, Zhao Y, Hu T, Ge X, Zhao G, Li Y, Zhang Y, Chen L. Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study. Lancet Diabetes Endocrinol. 2018 Aug;6(8):627-636. doi: 10.1016/S2213-8587(18)30105-0. Epub 2018 May 4.