The Multiple Dose of PK/PD Study of SHR2285 Tablets in Healthy Subjects

Study Overview
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Brief Summary
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The study is a randomized, single-blind, placebo-controlled, multiple-dose escalation Phase I trials. 2 dose groups were designed, 12 subjects in each dose group.The drug was administered single dose and multiple doses.

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

Conditions
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Thrombus

Intervention / Treatment
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* Drug: SHR2285 tablet
* 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; 50mmHg ≤DBP<90mmHg and 50 ≤ HR <110 beats / min. body mass index (BMI) between 18 to 28. Participant in general good health. No clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters. Exclusion Criteria: males or females, aged 18-45. subjects with no cardiovascular disease, sitting blood pressure: 90mmHg ≤SBP<140mmHg; 50mmHg ≤DBP<90mmHg and 50 ≤ HR <110 beats / min. body mass index (BMI) between 18 to 28. Participant in general good health. No clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters. Exclusion Criteria: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin > 1X ULN during screening/baseline. Serum creatinine> 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 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 (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive. 8.3 months prior to screening involved in any drug or medical device clinical studies or within 5 half-life of drugs before screening. 9.Female subjects who did not receive contraception at least 30 days before administration.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multiple dose of PK/PD Study of SHR2285 Tablets in Healthy Subjects
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR2285<br>Participants received one of 3 dose levels of SHR2285 administered as multiple oral doses. | Drug: SHR2285 tablet<br>* Pharmaceutical form: SHR2285 tablet Route of administration: single dose and multiple doses.<br>Drug: Placebo<br>* Pharmaceutical form: Placebo tablet Route of administration: single dose and multiple doses.<br>|
| Experimental: Placebo<br>Participants received one of 3 dose levels of placebo administered as multiple oral doses. | Drug: SHR2285 tablet<br>* Pharmaceutical form: SHR2285 tablet Route of administration: single dose and multiple doses.<br>Drug: Placebo<br>* Pharmaceutical form: Placebo tablet Route of administration: single dose and multiple doses.<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 multiple dose administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter will be evaluated. | Area under the plasma concentration versus time curve (AUC) for single dose of SHR2285. | Pre-dose to 3 days after single dose administration | 
| Maximum observed serum concentration (Cmax) for single dose of SHR2285. |  | Pre-dose to 3 days after single dose administration | 
| Time to maximum observed serum concentration (Tmax) for single dose of SHR2285. |  | Pre-dose to 3 days after single dose administration | 
| Apparent total clearance of the drug from plasma after oral administration (CL/F) for single dose of SHR2285. |  | Pre-dose to 3 days after single dose administration. | 
| Apparent volume of distribution after non-intravenous administration (V/F) for single dose of SHR2285 |  | Pre-dose to 3 days after single dose administration. | 
| Time to elimination half-life (T1/2) for single dose of SHR2285. |  | Pre-dose to 3 days after single dose administration | 
| Area under the plasma concentration versus time curve (AUC) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration | 
| Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration | 
| Steady state valley concentration (Ctrough，ss) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration | 
| Time to maximum observed serum concentration (Tmax) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration. | 
| Time to elimination half-life (T1/2) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration | 
| Steady-state apparent total clearance of the drug from plasma after oral administration (CLSS/F) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration. | 
| Steady-state apparent volume of distribution after non-intravenous administration (VSS/F) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration. | 
| Accumulation ratio (Racc) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration. | 
| Percentage of fluctuation (PTF%) for multiple dose of SHR2285. |  | Pre-dose to 2 days after multiple dose administration. | 
| PD parameter will be evaluated. | FXI activity; Change of APTT, PT, INR from baseline. | Pre-dose to 3 days after single dose administration. | 
| PD parameter will be evaluated. | FXI activity; Change of APTT, PT, INR from baseline. | Pre-dose to 2 days after multiple dose administration. |