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

Phase 1

Completed

• Conditions: Thrombus
• Interventions: Drug: SHR2285 tablet; Drug: Placebo

• Registration Number: NCT04229433
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-18
• Status Verified: 2020-01
• Study First Submitted QC: 2020-01-14
• Study First Posted: 2020-01-18
• Study Start: 2020-08-11
• Primary Completion: 2020-11-08
• Study Completion: 2020-11-08
• Last Update Submitted: 2021-05-21
• Last Update Posted: 2021-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. males or females, aged 18-45.
2. subjects with no cardiovascular disease, sitting blood pressure: 90mmHg ≤SBP<140mmHg; 50mmHg ≤DBP<90mmHg and 50 ≤ HR <110 beats / min.
3. body mass index (BMI) between 18 to 28.
4. Participant in general good health. No clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters.

Exclusion Criteria

1. males or females, aged 18-45.
2. subjects with no cardiovascular disease, sitting blood pressure: 90mmHg ≤SBP<140mmHg; 50mmHg ≤DBP<90mmHg and 50 ≤ HR <110 beats / min.
3. body mass index (BMI) between 18 to 28.
4. Participant in general good health. No clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters.

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin > 1X ULN during screening/baseline.
2. Serum creatinine> 1X ULN during screening/baseline.
3. Abnormal coagulation function.
4. A clinical history of coagulation dysfunction; subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
5. Subjects with severe head trauma or head surgery within 2 years or surgery within 3 months prior to the screening.
6. Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before administration.
7. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received one of 3 dose levels of placebo administered as multiple oral doses.
SHR2285	SHR2285 tablet	Participants received one of 3 dose levels of SHR2285 administered as multiple oral doses.
SHR2285	Placebo	Participants received one of 3 dose levels of SHR2285 administered as multiple oral doses.
Placebo	SHR2285 tablet	Participants received one of 3 dose levels of placebo administered as multiple oral doses.

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events and serious adverse events.	Pre-dose to 7 days after multiple dose administration.

Secondary Outcome Measures

Name	Time	Method
PK parameter will be evaluated.	Pre-dose to 3 days after single dose administration	Area under the plasma concentration versus time curve (AUC) for single dose of SHR2285.
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.
Area under the plasma concentration versus time curve (AUC) for multiple dose of SHR2285.	Pre-dose to 2 days after multiple 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
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.	Pre-dose to 2 days after multiple dose administration.	FXI activity; Change of APTT, PT, INR from baseline.

Trial Locations

Locations (1)

Zhejing Provincial People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China