The PK/PD Study of SHR2285 Tablets in Healthy Subjects

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

Thrombosis is a maladaptive process of vascular occlusion and remains a primary cause of cardiovascular morbidity and mortality, The dose-limiting issue with available anticoagulant therapies is bleeding. The primary objective of this study is to assess the safety and tolerability of SHR2285 tablets in healthy subjects. In addition, this study will provide information on Pharmacokinetics and Pharmacodynamics of SHR2285 tablets in healthy subjects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College 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 and 50mmHg ≤DBP<90mmHg;
3. body mass index (BMI) between 18 to 28, and a total body weight: male ≥50.0 kg and <90.0 kg; female ≥45.0 kg and <90.0 kg
4. Participant in general good health. No clinically significant findings in laboratory parameters or clinically significant abnormality on X-ray

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin > 1X ULN during screening/baseline;
2. Abnormal coagulation function;
3. A clinical history of coagulation dysfunction；subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
4. Subjects with severe trauma or surgery within 3 months prior to the screening；
5. Known blood donation within 30 days pre-dose; donating≥400 ml of blood 3 months pre-dose;
6. Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive;
7. 3 months prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs before screening;
8. Pregnant or Serum β-hCG > 5mIU/mL at baseline or women who are breastfeeding; etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR2285; Up to 7 cohorts of healthy subjects will receive a single dose of oral SHR2285 tablet.	Drug: SHR2285; Ascending dose oral adminstration
Experimental: Placebo; Up to 7 cohorts of healthy subjects will receive a single dose of oral placebo.	Drug: Placebo; Ascending dose oral adminstration

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 dose administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) of SHR2285	Pre-dose to 2 days after dose administration
Maximum observed serum concentration (Cmax) of SHR2285	Pre-dose to 2 days after dose administration
Time to maximum observed serum concentration (Tmax) of SHR2285	Pre-dose to 2 days after dose administration
Time to elimination half-life (T1/2) of SHR2285	Pre-dose to 2 days after dose administration
Apparent total clearance of the drug from plasma after oral administration(CL/F) of SHR2285	Pre-dose to 2 days after dose administration
Apparent volume of distribution after non-intravenous administration (V/F) of SHR2285	Pre-dose to 2 days after dose administration
Mean Residence Time(MRT) of SHR2285	Pre-dose to 2 days after dose administration
Change of APTT, PT, INR from baseline.	during Pre and Post-dose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Publications and helpful links

General Publications

• Chen R, Guan X, Hu P, Dong Y, Zhu Y, Zhang T, Zou J, Zhang S. First-In-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, a Small-Molecule Factor XIa Inhibitor in Healthy Subjects. Front Pharmacol. 2022 Feb 10;13:821363. doi: 10.3389/fphar.2022.821363. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): July 22, 2019
• Study Completion (Actual): July 22, 2019

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (Actual): December 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: May 20, 2021
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: SHR2285-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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