The PK/PD Study of SHR2285 Tablets in Healthy Subjects

Study Overview
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Brief Summary
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Thrombosis is a maladaptive process of vascular occlusion and remains a primary cause of cardiovascular morbidity and mortality, The dose-limiting issue with available anticoagulant therapies is bleeding. The primary objective of this study is to assess the safety and tolerability of SHR2285 tablets in healthy subjects. In addition, this study will provide information on Pharmacokinetics and Pharmacodynamics of SHR2285 tablets in healthy subjects.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR2285 Tablets in Healthy Subjects

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: SHR2285
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males or females, aged 18-45 subjects with no cardiovascular disease, sitting blood pressure: 90mmHg ≤SBP<140mmHg and 50mmHg ≤DBP<90mmHg; body mass index (BMI) between 18 to 28, and a total body weight: male ≥50.0 kg and <90.0 kg; female ≥45.0 kg and <90.0 kg Participant in general good health. No clinically significant findings in laboratory parameters or clinically significant abnormality on X-ray Exclusion Criteria: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin > 1X ULN during screening/baseline; Abnormal coagulation function; A clinical history of coagulation dysfunction；subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs. Subjects with severe trauma or surgery within 3 months prior to the screening； Known blood donation within 30 days pre-dose; donating≥400 ml of blood 3 months pre-dose; Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive; 3 months prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs before screening; Pregnant or Serum β-hCG > 5mIU/mL at baseline or women who are breastfeeding; etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR2285<br>Up to 7 cohorts of healthy subjects will receive a single dose of oral SHR2285 tablet. | Drug: SHR2285<br>* Ascending dose oral adminstration<br>|
| Experimental: Placebo<br>Up to 7 cohorts of healthy subjects will receive a single dose of oral placebo. | Drug: Placebo<br>* Ascending dose oral adminstration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events and serious adverse events |  | Pre-dose to 7 days after dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Maximum observed serum concentration (Cmax) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Time to maximum observed serum concentration (Tmax) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Time to elimination half-life (T1/2) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Apparent total clearance of the drug from plasma after oral administration(CL/F) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Apparent volume of distribution after non-intravenous administration (V/F) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Mean Residence Time(MRT) of SHR2285 |  | Pre-dose to 2 days after dose administration | 
| Change of APTT, PT, INR from baseline. |  | during Pre and Post-dose |