To Evaluate the Safety and Tolerability of Combined Administration of SHR2285 Tablets With Aspirin, Clopidogrel or Ticagrelor in Healthy Subjects

Study on the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SHR2285 Tablets Combined With Aspirin, Clopidogrel or Ticagrelor in Healthy Subjects

The study is a single-center，randomized, doubled-blinded, placebo-controlled, Only for SHR2285 Phase I trial. This study intends to enroll 52 healthy subjects, regardless of gender. The subjects are divided into three groups: A, B, and C, with 16 cases in each of groups A and B, and 20 cases in group C.

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: Aspirin、clopidogrel、placebo or SHR2285; Drug: Aspirin、clopidogrel、placebo or SHR2285; Drug: Aspirin、ticagrelor、placebo or SHR2285

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects, aged 18-55 (including boundary);
2. Body mass index (BMI) between 19 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，etc.
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 > 1.2 fold 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. .
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: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group A： Aspirin + Clopidogrel + placebo or SHR2285 (dose 1)	Drug: Aspirin、clopidogrel、placebo or SHR2285; groupA： Aspirin + clopidogrel + placebo or SHR2285 (dose 1) ； Drug: Aspirin、clopidogrel、placebo or SHR2285; groupB： Aspirin + clopidogrel + placebo or SHR2285 (dose 2)
Experimental: group B ：Aspirin + Clopidogrel + placebo or SHR2285 (dose 2)	Drug: Aspirin、clopidogrel、placebo or SHR2285; groupA： Aspirin + clopidogrel + placebo or SHR2285 (dose 1) ； Drug: Aspirin、clopidogrel、placebo or SHR2285; groupB： Aspirin + clopidogrel + placebo or SHR2285 (dose 2)
Experimental: group C： Aspirin + Ticagrelor + placebo or SHR2285	Drug: Aspirin、ticagrelor、placebo or SHR2285; groupC： Aspirin + ticagrelor + placebo or SHR2285

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events and severity of adverse events.	from the first dose to 48hours after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed serum concentration (Cmax) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite steady state after multiple administrations.	from Day1 to Day8 after the first dose
Tmax	Time to maximum observed serum concentration (Tmax) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations.	from Day1 to Day8 after the first dose
T1/2	Time to elimination half-life (T1/2) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations.	from Day1 to Day8 after the first dose
AUC0-last	Area under the plasma concentration versus time curve (AUC0-last) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations.	from Day1 to Day8 after the first dose
Cmax，ss	Steady-state peak concentration (Cmax，ss) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations.	from Day1 to Day8 after the first dose
Ctrough，ss	Steady state valley concentration (Ctrough，ss) for acetylsalicylic acid and its active metabolite salicylic acid, clopidogrel, ticagrelor and its active metabolite AR-C124910XX, SHR2285 and its active metabolite at steady state after multiple administrations.	from Day1 to Day8 after the first dose
FXI activity	Clotting factor XI (FXI) activity	from Day1 to Day8 after the first dose
APTT	Change of activated partial thromboplastin time (APTT) from baseline	from Day1 to Day8 after the first dose
PT	Change of prothrombin time (PT) from baseline	from Day1 to Day8 after the first dose
INR	Change of international normalization ratio (INR) from baseline	from Day1 to Day8 after the first dose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2021
• Primary Completion (Actual): October 19, 2021
• Study Completion (Actual): June 15, 2022

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: June 22, 2021
• First Posted (Actual): June 30, 2021

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor; Clopidogrel
• Other Study ID Numbers: SHR2285-106

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