Clinical trial NCT04472819: The Single, Multiple Dose and Food Effect Study of SHR2285 Tablets on Pharmacokinetics and Pharmacodynamics in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Thrombosis
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-15
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with adverse events and severity of adverse events.
timeFrame: Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration
measure: Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
timeFrame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Time to maximum observed serum concentration (Tmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
timeFrame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
timeFrame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
measure: Area under the plasma concentration versus time curve (AUC0-last) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
timeFrame: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
Secondary outcomes:
measure: Maximum observed serum concentration (Cmax) for single dose of SHR2285.
timeFrame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Time to maximum observed serum concentration (Tmax) for single dose of SHR2285.
timeFrame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Time to elimination half-life (T1/2) for single dose of SHR2285.
timeFrame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Area under the plasma concentration versus time curve (AUC0-last) for single dose of SHR2285.
timeFrame: Part 1:Pre-dose to day 3 after single dose administration and Part 2:Pre-dose to day 9 after multiple dose administration
measure: Steady-state peak concentration (Cmax，ss) for multiple dose of SHR2285.
timeFrame: Pre-dose to day 9 after multiple dose administration
measure: Steady state valley concentration (Ctrough，ss) for multiple dose of SHR2285.
timeFrame: Pre-dose to day 9 after multiple dose administration.
measure: Accumulation ratio (Racc) for multiple dose of SHR2285.
timeFrame: Pre-dose to day 9 after multiple dose administration
measure: Clotting factor XI (FXI) activity .
timeFrame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of activated partial thromboplastin time (APTT) from baseline.
timeFrame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of prothrombin time (PT) from baseline.
timeFrame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
measure: Change of international normalization ratio (INR) from baseline.
timeFrame: Part 1:Pre-dose to day 7 after single dose administration and Part 2:Pre-dose to day 14 after multiple dose administration
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
Study officials:
References: