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

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Hyperglycaemia (Diabetic)
• Intervention / Treatment: Drug: globalagliatin hydrochloride; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • the First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yabao Pharmaceutical Group
• Investigators: Study Director: Lei Yang, Yabao pharmaceutical Group Co.

Publications and helpful links

General Publications

• Zhao Y, Xie L, Zhang H, Zhou S, Liu Y, Chen J, Wang L, Wang L, Zhuo L, Wang Y, Ou N, Shao F. Tolerability, Safety, Pharmacokinetics, and Pharmacodynamics of SY-004, a Glucokinase Activator, in Healthy Chinese Adults: A Randomized, Phase Ia, Single-Ascending Dose Study. Clin Ther. 2022 Feb;44(2):269-281. doi: 10.1016/j.clinthera.2021.12.009. Epub 2022 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2017
• Primary Completion (Actual): September 25, 2017
• Study Completion (Actual): January 9, 2018

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 26, 2017
• First Posted (Actual): May 31, 2017

Study Record Updates

• Last Update Posted (Actual): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; T2DM; GKA
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Molecular Mechanisms of Pharmacological Action; Enzyme Activators; Globalagliatin
• Other Study ID Numbers: YB002003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No