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

Phase 1

Completed

• Conditions: Thrombosis
• Interventions: Drug: Aspirin、clopidogrel、placebo or SHR2285; Drug: Aspirin、ticagrelor、placebo or SHR2285

• Registration Number: NCT04945616
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-01
• Study First Submitted QC: 2021-06-22
• Study First Posted: 2021-06-30
• Study Start: 2021-07-13
• Primary Completion: 2021-10-19
• Status Verified: 2022-06
• Study Completion: 2022-06-15
• Last Update Submitted: 2022-06-30
• Last Update Posted: 2022-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group A： Aspirin + Clopidogrel + placebo or SHR2285 (dose 1)	Aspirin、clopidogrel、placebo or SHR2285	-
group C： Aspirin + Ticagrelor + placebo or SHR2285	Aspirin、ticagrelor、placebo or SHR2285	-
group B ：Aspirin + Clopidogrel + placebo or SHR2285 (dose 2)	Aspirin、clopidogrel、placebo or SHR2285	-

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events and severity of adverse events.	from the first dose to 48hours after the last dose

Secondary Outcome Measures

Name	Time	Method
Cmax	from Day1 to Day8 after the first dose	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.
Tmax	from Day1 to Day8 after the first dose	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.
T1/2	from Day1 to Day8 after the first dose	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.
AUC0-last	from Day1 to Day8 after the first dose	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.
Cmax，ss	from Day1 to Day8 after the first dose	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.
Ctrough，ss	from Day1 to Day8 after the first dose	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.
FXI activity	from Day1 to Day8 after the first dose	Clotting factor XI (FXI) activity
PT	from Day1 to Day8 after the first dose	Change of prothrombin time (PT) from baseline
APTT	from Day1 to Day8 after the first dose	Change of activated partial thromboplastin time (APTT) from baseline
INR	from Day1 to Day8 after the first dose	Change of international normalization ratio (INR) from baseline

Trial Locations

Locations (1)

Nanjing Drum Tower Hospital; 🇨🇳 Nanjing, Jiangsu, China