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

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

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.

Study Overview

• Status: Completed
• Conditions: Thrombus
• Intervention / Treatment: Drug: SHR2285 tablet; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Zhejing Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR2285; Participants received one of 3 dose levels of SHR2285 administered as multiple oral doses.	Drug: SHR2285 tablet; Pharmaceutical form: SHR2285 tablet Route of administration: single dose and multiple doses.; Drug: Placebo; Pharmaceutical form: Placebo tablet Route of administration: single dose and multiple doses.
EXPERIMENTAL: Placebo; Participants received one of 3 dose levels of placebo administered as multiple oral doses.	Drug: SHR2285 tablet; Pharmaceutical form: SHR2285 tablet Route of administration: single dose and multiple doses.; Drug: Placebo; Pharmaceutical form: Placebo tablet Route of administration: single dose and multiple doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 11, 2020
• Primary Completion (ACTUAL): November 8, 2020
• Study Completion (ACTUAL): November 8, 2020

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (ACTUAL): January 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2021
• Last Update Submitted That Met QC Criteria: May 21, 2021
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: SHR2285-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No