Multiple-dose Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Pharmacodynamics of HSK7653 in T2DM

Study Overview
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Brief Summary
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To evaluate the safety, tolerability and pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of HSK7653 tablets in Type 2 Diabetes Mellitus Patients.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo Control, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HSK7653 in Type 2 Diabetes Mellitus Patients

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: HSK7653 10 mg
* Drug: HSK7653 25 mg
* Drug: HSK7653 50 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and Age ≤70 years T2DM patients, Control the blood glucose level only with diet and exercise in last 3 months; BMI ≥19 and BMI ≤ 35 kg/m2 (Body Mass Index) HbA1c ≥7.0% and HbA1c <10.0% FPG <13.9 mmol/L Exclusion Criteria: Non-type 2 diabetes mellitus: Type 1 diabetes mellitus, gestational diabetes history; History of acute complications of diabetes (diabetic ketoacidosis, diabetic hyperglycemia hyperosmolar syndrome or lactic acidosis); History of chronic complications of severe diabetes (retinal proliferative disease, severe diabetic neuropathy or intermittent claudication confirmed by fundus examination during screening); Patients who used systemic glucocorticoids within 3 months prior to screening had severe infections or major surgeries and transplants within 3 months; Three or more episodes of hypoglycemia occurred in the six months prior to screening; History of hyperthyroidism within 6 months before screening; Severe cardiovascular disease. ; Medical conditions that may significantly affect drug absorption, distribution, metabolism, and excretion within 2 weeks prior to screening; Liver function tests abnormal; Moderate or severe renal impairment; Medical history or clinical evidence of pancreatic injury or pancreatitis, or abnormalities in lipase and amylase judged by investigators to be clinically significant; Patients with a history of hypertension who regularly take antihypertensive therapy for over 4 weeks still have poor control, SBP > 160 mmHg and (or) DBP > 100 mmHg; Patients with uncontrolled hyperlipidemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK7653 10 mg<br> | Drug: HSK7653 10 mg<br>* Tablet, HSK7653 10 mg Q2W, 12 weeks<br>|
| Experimental: HSK7653 25 mg<br> | Drug: HSK7653 25 mg<br>* Tablet, HSK7653 25 mg Q2W, 12 weeks<br>|
| Experimental: HSK7653 50 mg<br> | Drug: HSK7653 50 mg<br>* Tablet, HSK7653 50 mg Q2W, 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Tablet, 0 mg Q2W, 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Assessment by adverse event monitoring, 12 lead ECGs, vital signs and laboratory measurements. | From baseline to up to 2 weeks after last dose for a total of approximately 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) of HSK7653 | Cmax of HSK7653 after first dose and multi-dose administration | Day 1 to Day 43 | 
| Area under the plasma concentration versus time curve (AUC) of HSK7653 | AUC of HSK7653 after first dose and multi-dose administration | Day 1 to Day 43 | 
| Half-life (t1/2) of HSK7653 | T1/2 of HSK7653 after single-dose and multi-dose administration | Day 1 to Day 43 | 
| Change from baseline in dipeptidyl peptidase-IV (DPP-4) inhibition rate | Change from baseline in dipeptidyl peptidase-IV (DPP-4) inhibition rate after single-dose and multi-dose administration of HSK7653 | Day 1 to Day 84 | 
| Change from baseline in GLP-1 | Change from baseline in GLP-1 after single-dose and multi-dose administration of HSK7653 | Day 1 to Day 84 | 
| Change from baseline of fasting plasma glucose | Change from baseline in fasting plasma glucose after multi-dose administration of HSK7653 | Day 1 to Day 84 | 
| Change from baseline of HbA1c | Change from baseline in HbA1c after multi-dose administration of HSK7653 | Day 1 to Day 84 |