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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 2
- 主要终点
- Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
SHR2285 Part 1A
Participant received one of 7 dose levels of SHR2285 tablet as single-dose oral administration
干预措施: SHR2285 tablet (Drug)
Placebo Part 1A
Single ascending doses of placebo orally
干预措施: Placebo (Drug)
SHR2285 Part 1B
Participant received one dose of SHR2285 tablet as single-dose oral administration
干预措施: SHR2285 tablet (Drug)
Placebo Part 1B
Single doses of placebo orally
干预措施: Placebo (Drug)
SHR2285 Part 2
Participant received one of 4 dose levels of SHR2285 tablet as multi-dose oral administration
干预措施: SHR2285 tablet (Drug)
Placebo Part 2
Multiple ascending doses of placebo orally
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum observed serum concentration (Cmax) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
时间窗: 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.
时间窗: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
Number of subjects with adverse events and severity of adverse events.
时间窗: Part 1: Pre-dose to day 7 after single dose administration and Part 2: Pre-dose to day 14after multiple dose administration
Time to elimination half-life (T1/2) for Food Effect of SHR2285 on pharmacokinetics parameters in healthy subjects.
时间窗: 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.
时间窗: Part 1A: Pre-dose to day 7 after single dose administration and Part 1B: Pre-dose to day 7 after single dose administration
次要结局
- 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)
- 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)
- 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 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 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 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)
- 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)