The Single, Multiple Dose and Food Effect Study of SHR2285 Tablets on Pharmacokinetics and Pharmacodynamics in Healthy Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy subjects, aged 18-55 (including boundary);
-
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;
-
Participant with no clinically significant findings in vital signs, physical examination, 12-lead ECG ,X-ray and laboratory parameters.
-
Understand the study procedures and methods, voluntary to participate in the study and signed the informed consent.
Exclusion Criteria:
-
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin/direct bilirubin > upper limit of normal (ULN) during screening/baseline.
-
Serum creatinine> ULN during screening/baseline.
-
Positive faecal occult blood
-
Abnormal coagulation function.
-
A clinical history of coagulation dysfunction; subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
-
Subjects with severe head trauma or head surgery within 2 years or surgery within 3 months prior to the screening.
-
Blood donation or blood loss within 1 month≥200 mLor≥400 mL within 3 months before administration.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University First Hospital | Beijing | Beijing | China | 100034 |
| 2 | The Third Xiangya Hospital of Central South University | Changsha | Hunan | China | 410006 |
Sponsors and Collaborators
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR2285-104