To Evaluate the Safety and Tolerability of Combined Administration of SHR2285 Tablets With Aspirin, Clopidogrel or Ticagrelor in Healthy Subjects

Study Overview
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Brief Summary
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The study is a single-center，randomized, doubled-blinded, placebo-controlled, Only for SHR2285 Phase I trial. This study intends to enroll 52 healthy subjects, regardless of gender. The subjects are divided into three groups: A, B, and C, with 16 cases in each of groups A and B, and 20 cases in group C.

Official Title
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Study on the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR2285 Tablets Combined With Aspirin, Clopidogrel or Ticagrelor in Healthy Subjects

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: Aspirin、clopidogrel、placebo or SHR2285
* Drug: Aspirin、clopidogrel、placebo or SHR2285
* Drug: Aspirin、ticagrelor、placebo or SHR2285


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, aged 18-55 (including boundary); Body mass index (BMI) between 19 to 28 kg/m2 (including boundary), male body weight ≥50 kg and <90 kg , female body weight ≥45kg and <90kg; Participant with no clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters，etc. Understand the study procedures and methods, voluntary to participate in the study and signed the informed consent. Exclusion Criteria: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin > 1.2 fold ULN during screening/baseline. Serum creatinine> ULN during screening/baseline. Positive faecal occult blood Abnormal coagulation function. A clinical history of coagulation dysfunction; subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs. Subjects with severe head trauma or head surgery within 2 years or surgery within 3 months prior to the screening. Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before administration. Human immunodeficiency virus antibody, syphilis serological examination, hepatitis b virus surface antigen, hepatitis c virus antibody were positive. 3 months prior to screening involved in any drug or medical device clinical studies. . Female subjects who did not receive contraception at least 30 days before administration and etc.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group A： Aspirin + Clopidogrel + placebo or SHR2285 (dose 1)<br> | Drug: Aspirin、clopidogrel、placebo or SHR2285<br>* groupA： Aspirin + clopidogrel + placebo or SHR2285 (dose 1) ；<br>|
| Experimental: group B ：Aspirin + Clopidogrel + placebo or SHR2285 (dose 2)<br> | Drug: Aspirin、clopidogrel、placebo or SHR2285<br>* groupB： Aspirin + clopidogrel + placebo or SHR2285 (dose 2)<br>|
| Experimental: group C： Aspirin + Ticagrelor + placebo or SHR2285<br> | Drug: Aspirin、ticagrelor、placebo or SHR2285<br>* groupC： Aspirin + ticagrelor + placebo or SHR2285<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 severity of adverse events. |  | from the first dose to 48hours after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed serum concentration (Cmax) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| Tmax | Time to maximum observed serum concentration (Tmax) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| T1/2 | Time to elimination half-life (T1/2) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| AUC0-last | Area under the plasma concentration versus time curve (AUC0-last) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| Cmax，ss | Steady-state peak concentration (Cmax，ss) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| Ctrough，ss | Steady state valley concentration (Ctrough，ss) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations. | from Day1 to Day8 after the first dose | 
| FXI activity | Clotting factor XI (FXI) activity | from Day1 to Day8 after the first dose | 
| APTT | Change of activated partial thromboplastin time (APTT) from baseline | from Day1 to Day8 after the first dose | 
| PT | Change of prothrombin time (PT) from baseline | from Day1 to Day8 after the first dose | 
| INR | Change of international normalization ratio (INR) from baseline | from Day1 to Day8 after the first dose |