A Phase I Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Globalagliatin Hydrochloride After Multiple Ascending Doses in Patients With Type 2 Diabetes Mellitus
Overview
- Phase
- Phase 1
- Intervention
- Globalagliatin Hydrochloride
- Conditions
- Hyperglycaemia (Diabetic)
- Sponsor
- Yabao Pharmaceutical Group
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- the mean change in glucose area under curve (AUC) from baseline.
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a phase I placebo-controlled study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of Globalagliatin Hydrochloride (SY-004) after Multiple Ascending Doses in patients with Type 2 Diabetes Mellitus (T2DM).
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, Globalagliatin( the active ingredient in SY-004 capsule) is being investigated for use as a treatment for T2DM patients. This is a phase I placebo-controlled study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of Globalagliatin Hydrochloride (SY-004) after Multiple Ascending Doses in patients with Type 2 Diabetes Mellitus.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Sex：Male and Female；
- •Age：≥18，≤70；
- •Have T2DM prior to entering the trial based on the disease diagnostic criteria (WHO, 1999), and currently being treated with diet and exercise only or in combined with a stable dose of metformin for at least 8 weeks.
- •18 kg/m2≤BMI≤35 kg/m2 at screening.
- •7% ≤ HbA1c ≤11% at screening.
- •7 mmol/L≤FPG≤13.3mmol/L at baseline.
- •The venous access is normal, and blood samples can be collected according to the protocol.
- •Have given written informed consent to participate in this study.
- •Are well motivated, capable, and willing to communicate with the investigator and complete all the requirements according to the protocol.
Exclusion Criteria
- •Personnel and their direct relatives of the clinical research unit and its related facilities. Direct relatives mean all biologically and by law related relatives, including spouse, parent, child and sibling,
- •Have been diagnosed with type 1 diabetes, or gestational diabetes mellitus, or a specific type of diabetes mellitus.
- •Clinically significant coronary events or symptoms within 6 months prior to study entry.
- •Clinically significant peripheral vascular disease.
- •Clinical evidence of active diabetic proliferative retinopathy.
- •Known clinically significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis.
- •With a history of diabetes or diabetic ketoacidosis, lactic acidosis, hyperosmolar nonketotic coma history.
- •Have severe hypoglycemia occurred before the screening with unknown causes (need other people to help restore) or the frequency of hypoglycemia, such as 3 or more hypoglycemic events(blood glucose ≤3.9mmol/L) within 1 months before screening or hypoglycemia related symptoms.
- •Continuous use of insulin for more than 1 month in last year.
- •Have any disorder or unstable situation of the endocrine system, immune system or other diseases impaired blood sugar(such as Hyperthyroidism, acromegaly, Cushing syndrome) that are required treatment
Arms & Interventions
Globalagliatin Hydrochloride (SY-004)
If subjects tolerate 20mg of Globalagliatin Hydrochloride (SY-004) for 7 days, dose escalation will occur in the following order of 40mg, 80mg and 120mg at weekly intervals until patients get intolerant or blood glucose controlled well or reach the maximal dose 120mg.
Intervention: Globalagliatin Hydrochloride
Placebo
If subjects tolerate 20mg of Placebo for 7 days, dose escalation will occur in the following order of 40mg, 80mg and 120mg at weekly intervals until patients get intolerant or blood glucose controlled well or reach the maximal dose 120mg.
Intervention: Placebo
Outcomes
Primary Outcomes
the mean change in glucose area under curve (AUC) from baseline.
Time Frame: 28 days
Compared with placebo, the mean change in glucose AUC from baseline at D28.
Secondary Outcomes
- the fasting plasma glucose from baseline(7, 14, 21, 28 days)
- the changes of MMTT (mixed-meal tolerance test) results from baseline(28 days)
- the mean changes of average 7-points blood glucose profiles from baseline(7, 14, 21, 28 days)
- the mean changes of post-prandial blood glucose from baseline(7, 14, 21, 28 days)
- the mean changes of average 14-points blood glucose profiles from baseline(7, 14, 21, 28 days)