A Trial of SHR2285 in Healthy Subjects

Study Overview
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Brief Summary
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This is a phase 1 open-label study

Detailed Description
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This is a phase 1 open-label study. The objective of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of oral administered SHR2285 in healthy subjects

Official Title
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A Phase 1, Single Center, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR2285 Single Oral Administration in Healthy Caucasian Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: SHR2285


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the trial procedures and possible adverse events, volunteers to participate in the trial, and provides written informed consent. Be able to comply with all the requirements and able to complete the study. Male or female aged between 18 years and 55 years (inclusive) at the date of signed consent form. No clinically significant abnormalities in medical history, general physical examination, vital signs, and laboratory tests. Men and women of childbearing potential (WOCBP) must agree to take effective contraceptive methods and have no plan to have a child from signing the consent form to 16 weeks after IP administration. Exclusion Criteria: Receipt of any other investigational drugs or medical devices within 3 months prior to screening (according to the date of signed consent form). History of illicit or prescription drug abuse or addiction within one year of screening, or positive urine drug screen at screening and Day-1. The urine drug screen may be repeated at the discretion of the investigator and the reason for repeat needs to be documented clearly (e.g., suspicion of false positive due to diet). Receipt of any other investigational drugs or medical devices within 3 months prior to screening (from the date of signed consent form).

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Three different cohorts can enroll healthy Caucasian participants; males and females in each cohort separately.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose of SHR2285<br>The subjects will receive a single dose of SHR2285 (cohort 1). | Drug: SHR2285<br>* SHR2285 is a selective inhibition of human FXIa small molecule compound.<br>|
| Experimental: Medium dose of SHR2285<br>The subjects will receive a single dose of SHR2285 (cohort 2). | Drug: SHR2285<br>* SHR2285 is a selective inhibition of human FXIa small molecule compound.<br>|
| Experimental: High dose of SHR2285<br>The subjects will receive a single dose of SHR2285 (cohort 3). | Drug: SHR2285<br>* SHR2285 is a selective inhibition of human FXIa small molecule compound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Incidence and severity of adverse events | Start of Treatment to end of study (approximately 7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics-AUC0-last | Area under the concentration-time curve from time 0 to last time point after SHR2285 administration | Start of Treatment to outpatient (approximately 3 days) | 
| Pharmacokinetics-AUC0-inf | Area under the concentration-time curve from time 0 to infinity after SHR2285 administration | Start of Treatment to outpatient (approximately 3 days) | 
| Pharmacokinetics-Tmax | Time to Cmax of SHR2285 and its metabolite SHR164471 | Up to 3 days | 
| Pharmacokinetics-Cmax | Maximum observed concentration of SHR2285 and its metabolite SHR164471 | Up to 3 days | 
| Pharmacokinetics-CL/F | Apparent clearance of SHR2285 and its metabolite SHR164471 | Up to 3 days | 
| Pharmacokinetics-Vz/F | Apparent volume of distribution during terminal phase of SHR2285 and its metabolite SHR164471 | Up to 3 days | 
| Pharmacokinetics-t1/2 | Terminal elimination half-life of SHR2285 and its metabolite SHR164471 | Up to 3 days | 
| Coagulation factor XI (FXI) activity | Coagulation factor XI (FXI) activity | Up to 3 days | 
| Percentage change of coagulation factor XI (FXI) activity thromboplastin time (APTT) and fold change from baseline | Percentage change of coagulation factor XI (FXI) activity | Up to 3 days | 
| Activated partial thromboplastin time | Activated partial thromboplastin time | Up to 3 days | 
| Fold change of activated partial thromboplastin time from baseline | Fold change of activated partial thromboplastin time from baseline | Up to 3 days | 
| Prothrombin time | Prothrombin time | Up to 3 days | 
| Fold change of prothrombin time from baseline | Fold change of prothrombin time from baseline | Up to 3 days | 
| International normalized ratio | International normalized ratio | Up to 3 days | 
| Fold change of international normalized ratio from baseline | Fold change of international normalized ratio from baseline | Up to 3 days |