The Single, Multiple Dose and Food Effect Study of SHR2285 Tablets on Pharmacokinetics and Pharmacodynamics in Healthy Subjects

Study Overview
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Brief Summary
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The study is a randomized, doubled-blinded, placebo-controlled, Phase I trials. The study is divided into two parts. The first part is a single-dose escalated study (SAD,part 1A ) and food effect study (SAD, part 1B ) in healthy subjects. The second part is a multi-dose escalated study (MAD) in healthy subjects.

Official Title
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A Phase I, Randomized, Double -Blinded, Placebo-Controlled, Single and Multiple Dose and Food Effect 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 tablet
* Drug: Placebo


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 18 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. 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 > upper limit of normal (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. 9.3 months prior to screening involved in any drug or medical device clinical studies or within 5 half-life of drugs before screening. 10.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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR2285 Part 1A<br>Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration | Drug: SHR2285 tablet<br>* single dose or multi-dose<br>|
| Placebo Comparator: Placebo Part 1A<br>Single ascending doses of placebo orally | Drug: Placebo<br>* single dose or multi-dose<br>|
| Experimental: SHR2285 Part 1B<br>Participant received one dose of SHR2285 tablet as single-dose oral administration | Drug: SHR2285 tablet<br>* single dose or multi-dose<br>|
| Placebo Comparator: Placebo Part 1B<br>Single doses of placebo orally | Drug: Placebo<br>* single dose or multi-dose<br>|
| Experimental: SHR2285 Part 2<br>Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration | Drug: SHR2285 tablet<br>* single dose or multi-dose<br>|
| Placebo Comparator: Placebo Part 2<br>Multiple ascending doses of placebo orally | Drug: Placebo<br>* single dose or multi-dose<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. |  | Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration | 
| Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects. |  | Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration | 
| Time to maximum observed serum concentration (Tmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects. |  | Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration | 
| Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects. |  | Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration | 
| Area under the plasma concentration versus time curve (AUC0-last) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects. |  | Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) for single dose of SHR2285. |  | Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration | 
| Time to maximum observed serum concentration (Tmax) for single dose of SHR2285. |  | Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration | 
| Time to elimination half-life (T1/2) for single dose of SHR2285. |  | Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration | 
| Area under the plasma concentration versus time curve (AUC0-last) for single dose of SHR2285. |  | Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration | 
| Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285. |  | Pre-dose to day 9 after multiple dose administration | 
| Steady state valley concentration (Ctrough，ss) for multiple dose of SHR2285. |  | Pre-dose to day 9 after multiple dose administration. | 
| Accumulation ratio (Racc) for multiple dose of SHR2285. |  | Pre-dose to day 9 after multiple dose administration | 
| Clotting factor XI (FXI) activity . |  | Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration | 
| Change of activated partial thromboplastin time (APTT) from baseline. |  | Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration | 
| Change of prothrombin time (PT) from baseline. |  | Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration | 
| Change of international normalization ratio (INR) from baseline. |  | Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration |