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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
  • Hunan
    • Changsha, Hunan, China, 410006
      • The Third Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects, aged 18-55 (including boundary);
2. 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;
3. Participant with no clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters.
4. Understand the study procedures and methods, voluntary to participate in the study and signed the informed consent.

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin > upper limit of normal (ULN) during screening/baseline.
2. Serum creatinine> ULN during screening/baseline.
3. Positive faecal occult blood
4. Abnormal coagulation function.
5. A clinical history of coagulation dysfunction; subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
6. Subjects with severe head trauma or head surgery within 2 years or surgery within 3 months prior to the screening.
7. Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before administration.
8. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR2285 Part 1A; Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration	Drug: SHR2285 tablet; single dose or multi-dose
PLACEBO_COMPARATOR: Placebo Part 1A; Single ascending doses of placebo orally	Drug: Placebo; single dose or multi-dose
EXPERIMENTAL: SHR2285 Part 1B; Participant received one dose of SHR2285 tablet as single-dose oral administration	Drug: SHR2285 tablet; single dose or multi-dose
PLACEBO_COMPARATOR: Placebo Part 1B; Single doses of placebo orally	Drug: Placebo; single dose or multi-dose
EXPERIMENTAL: SHR2285 Part 2; Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration	Drug: SHR2285 tablet; single dose or multi-dose
PLACEBO_COMPARATOR: Placebo Part 2; Multiple ascending doses of placebo orally	Drug: Placebo; single dose or multi-dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2020
• Primary Completion (ACTUAL): May 31, 2021
• Study Completion (ACTUAL): May 31, 2021

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 12, 2020
• First Posted (ACTUAL): July 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 26, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: SHR2285-104

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