Clinical trial NCT03171623: The Assessment of Single-Dose Safety,Tolerability, Pharmacokinetics and Pharmacodynamic of Globalagliatin Hydrochloride
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hyperglycaemia (Diabetic)
Healthy Volunteers
Keywords: T2DM
Diabetes
GKA
Lead sponsor: Yabao Pharmaceutical Group
Sponsor class: INDUSTRY
First posted: 2017-05-31
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of single dose of SY-004
timeFrame: 14 day post-dose
Secondary outcomes:
measure: AUC of SY-004 following oral administration of single ascending dose
timeFrame: up to 168 hours post-dose
measure: Cmax of SY-004 following oral administration of single ascending dose.
timeFrame: up to 168 hours post-dose
measure: T1/2 of SY-004 following oral administration of single ascending dose
timeFrame: up to 168 hours post-dose
measure: CL/F of SY-004 following oral administration of single ascending dose
timeFrame: up to 168 hours post-dose
measure: glucose levels following single dose of SY-004
timeFrame: up to 48 hours post-dose
measure: insulin secretion following single dose of SY-004
timeFrame: up to 11 hours post-dose
measure: C-peptide secretion following single dose of SY-004
timeFrame: up to 11 hour post-dose
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Yabao pharmaceutical Group Co.
name: Lei Yang
role: STUDY_DIRECTOR
References:
citation: 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.