The Assessment of Single-Dose Safety,Tolerability, Pharmacokinetics and Pharmacodynamic of Globalagliatin Hydrochloride

Study Overview
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Brief Summary
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This is a phase 1 randomized,double-blind,placebo-controlled study with single oral dose of globalagliatin hydrochloride (SY-004) administered to chinese healthy subjects to evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of globalagliatin hydrochloride (SY-004).

Detailed Description
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Glucokinase is a characteristic hexokinase isoenzyme in hepatocytes that catalyzes the first step in glucose metabolism. In addition to its role in glucose metabolism, glucokinase is expressed in pancreatic islet beta cells where it acts as a glucose sensor for insulin release. Activation of glucokinase increases the glucose sensitivity of insulin secretion, effectively lowering the glucose threshold for insulin secretion. Because of its potential to enhance insulin secretion and affect hepatic glucose metabolism, is being investigated for use as a treatment for hyperglycaemia,glubalagliatin( the active ingredient in SY-004 capsule) is being investigated for use as a treatment for T2DM patients. This is a phase 1 randomized,double-blind,placebo-controlled study with single oral dose of SY-004 administered to chinese healthy subjects to evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of SY-004.

Official Title
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A Randomised,Double-blind,Placebo-controlled Study to Assessment of Single-Dose Safety,Tolerability, Pharmacokinetics and Pharmacodynamic of Globalagliatin Hydrochloride (SY-004) in Chinese Healthy Subjects

Conditions
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Hyperglycaemia (Diabetic), Healthy Volunteers

Intervention / Treatment
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* Drug: globalagliatin hydrochloride
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males and females between the ages of 18 and 65 years, inclusive, healthy subjects A screening body mass index (BMI) of 18 to 26 kg/m2 inclusive, body weight above 50kg FPG≥3.9mmol/L and <6.1 mmol/L Have medical history, physical examination, laboratory tests and other relative test results within the normal range or with abnormalities deemed clinically insignificant by the investigator. Have given written informed consent. The subjects took effective contraceptive measures, and had no birth plan within 3 months.Female subjects should be non lactating, negative pregnancy test, or no fertility potential (Women who were 12 months of menopause or without uterus were found to have no potential for pregnancy ) Exclusion Criteria: There is a serious history of systemic disease, or a family history (including cardiovascular system, digestive system, urinary system, etc.) Have taken a special diet or exercise before 48 hours of drug administration or other factors are capable of significantly altering the absorption, or metabolism or elimination of drugs. A significant abnormality in ALT,AST or other lab test results Frontal chest X light result is clinical significantly abnormal. Have known intolerance of or allergies to glucokinase activators, or related compounds. Have known allergies to other compounds or biologic products. Have a major surgery in the last 4 weeks before dosing. To inoculate any live vaccine within 4 weeks before drug administration. Have a history of drug abuse Use any prescription drugs within 4 weeks prior to administration or use OTC or traditional Chinese medicine within 1 weeks before enrollment. Regular drinkers within 6 months before or during the trial (Subjects who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) [1 unit = 360 mL of beer; or 150 mL of wine; or 45 mL of distilled spirits]) The amount of daily cigarette smoking was more than 5/day in last 3 months, or subjects unwilling to stop cigarette consumption during the trial. Are enrolled in 4 or more clinical trials within last year, or participated any clinical trail within 3 months before enrollment ; plan to donate blood or blood donation of 450 mL or more in the last 3 months; or have blood transfusion 4 weeks before the trial. An clinical significant abnormality in the 12-lead ECG at screening or baseline: QT interval> 450 ms Subjects deemed unsuitable by the Investigator for low compliance or any other reason. investigator and their immediate families.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SY-004 2mg<br>SY-004 (globalagliatin hydrochloride) 2mg by mouth, single dose | Drug: globalagliatin hydrochloride<br>* orally administration, single dose<br>* Other names: SY-004 capsule;|
| Placebo Comparator: SY-004 20mg&placebo<br>SY-004 (globalagliatin hydrochloride) 20mg or placebo by mouth, single dose | Drug: globalagliatin hydrochloride<br>* orally administration, single dose<br>* Other names: SY-004 capsule;Drug: placebo<br>* orally administration, single dose<br>|
| Placebo Comparator: SY-004 40mg&placebo<br>SY-004 (globalagliatin hydrochloride) 40mg or placebo by mouth, single dose | Drug: globalagliatin hydrochloride<br>* orally administration, single dose<br>* Other names: SY-004 capsule;Drug: placebo<br>* orally administration, single dose<br>|
| Placebo Comparator: SY-004 80mg&placebo<br>SY-004 (globalagliatin hydrochloride) 80mg or placebo by mouth, single dose | Drug: globalagliatin hydrochloride<br>* orally administration, single dose<br>* Other names: SY-004 capsule;Drug: placebo<br>* orally administration, single dose<br>|
| Placebo Comparator: SY-004 120mg&placebo<br>SY-004(globalagliatin hydrochloride) 120mg or placebo by mouth, single dose | Drug: globalagliatin hydrochloride<br>* orally administration, single dose<br>* Other names: SY-004 capsule;Drug: placebo<br>* orally administration, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of single dose of SY-004 | number of patients with adverse events and changes from baseline in vital signs, ECG and clinical labs (blood chemistry, hematology and urinalysis) | 14 day post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of SY-004 following oral administration of single ascending dose | to measure the study drug concentration in blood and urine samples to be collected after drug administration. | up to 168 hours post-dose | 
| Cmax of SY-004 following oral administration of single ascending dose. | to measure the study drug concentration in blood and urine samples to be collected after drug administration. | up to 168 hours post-dose | 
| T1/2 of SY-004 following oral administration of single ascending dose | to measure the study drug concentration in blood and urine samples to be collected after drug administration. | up to 168 hours post-dose | 
| CL/F of SY-004 following oral administration of single ascending dose | to measure the study drug concentration in blood and urine samples to be collected after drug administration. | up to 168 hours post-dose | 
| glucose levels following single dose of SY-004 | FPG AUC | up to 48 hours post-dose | 
| insulin secretion following single dose of SY-004 | insulin changes | up to 11 hours post-dose | 
| C-peptide secretion following single dose of SY-004 | C-peptide change | up to 11 hour post-dose | 

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