Clinical trial NCT03769831: The PK/PD Study of SHR2285 Tablets in Healthy Subjects
Official title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose 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: 2018-12-10
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Thrombosis is a maladaptive process of vascular occlusion and remains a primary cause of cardiovascular morbidity and mortality, The dose-limiting issue with available anticoagulant therapies is bleeding. The primary objective of this study is to assess the safety and tolerability of SHR2285 tablets in healthy subjects. In addition, this study will provide information on Pharmacokinetics and Pharmacodynamics of SHR2285 tablets in healthy subjects.


Eligibility criteria: Inclusion Criteria:

1. males or females, aged 18-45
2. subjects with no cardiovascular disease, sitting blood pressure: 90mmHg ≤SBP\<140mmHg and 50mmHg ≤DBP\<90mmHg;
3. body mass index (BMI) between 18 to 28, and a total body weight: male ≥50.0 kg and \<90.0 kg; female ≥45.0 kg and \<90.0 kg
4. Participant in general good health. No clinically significant findings in laboratory parameters or clinically significant abnormality on X-ray

Exclusion Criteria:

1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin \> 1X ULN during screening/baseline;
2. Abnormal coagulation function;
3. A clinical history of coagulation dysfunction；subjects with adverse reaction of antiplatelet drugs or anticoagulant drugs.
4. Subjects with severe trauma or surgery within 3 months prior to the screening；
5. Known blood donation within 30 days pre-dose; donating≥400 ml of blood 3 months pre-dose;
6. Human immunodeficiency virus antibody (HIV-ab), syphilis serological examination, hepatitis b virus surface antigen (HBsAg), hepatitis c virus antibody (HCV-ab) were positive;
7. 3 months prior to screening involved in any drug or medical device clinical subjects, or within 5 half-life of drugs before screening;
8. Pregnant or Serum β-hCG \> 5mIU/mL at baseline or women who are breastfeeding; etc.

Primary outcomes:
measure: Number of subjects with adverse events and serious adverse events
timeFrame: Pre-dose to 7 days after dose administration
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Maximum observed serum concentration (Cmax) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Time to maximum observed serum concentration (Tmax) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Time to elimination half-life (T1/2) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Apparent total clearance of the drug from plasma after oral administration(CL/F) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Apparent volume of distribution after non-intravenous administration (V/F) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Mean Residence Time(MRT) of SHR2285
timeFrame: Pre-dose to 2 days after dose administration
measure: Change of APTT, PT, INR from baseline.
timeFrame: during Pre and Post-dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References:
citation: Chen R, Guan X, Hu P, Dong Y, Zhu Y, Zhang T, Zou J, Zhang S. First-In-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, a Small-Molecule Factor XIa Inhibitor in Healthy Subjects. Front Pharmacol. 2022 Feb 10;13:821363. doi: 10.3389/fphar.2022.821363. eCollection 2022.