The Impact of Genotype on Pharmacokinetics and Antiplatelet Effects of Ticagrelor in Healthy Chinese
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 主要终点
- Genome-wide genotyping in 51 healthy Chinese
研究概览
简要总结
This study is a open and single center clinical trial in healthy Chinese.The objective of the study is to clarify the pharmacokinetics characteristics and antiplatelet effects of ticagrelor in Chinese and to investigate the impact of genotype.
详细描述
This is an open-label, single-does, nonrandomized study of ticagrelor in healthy volunteers carried out at a single center. Written informed consent will be obtained from all volunteers before initiation of the study. The study is approved by the Research Ethic Committee of Guangdong General Hospital. Fifty-one healthy Chinese will be recruited.
Venous blood will be collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48h after taking 180mg ticagrelor orally. Urine collection intervals are at predose and 0 to 2, 2 to 4, 4 to 6, 6 to 9, 9 to 12, 12 to 16 and 16 to 24h after dosing. The concentration of ticagrelor and its metabolites will be analyzed using a separately validated liquid chromatography technique with tandem mass spectrometric detection (LC-MS/MS).
Besides，the basic principle of population pharmacodynamics(PPD) is applied to evaluate antiplatelet effects. Adenosine diphosphate(ADP)-stimulated platelet aggregation will be assessed at baseline, and 0.5h/1h, 2h, 4h/8h/24h, 48h/3d/5d and 7d after dosing.
The effects of genetic variants on antiplatelet and pharmacokinetic response to ticagrelor are investigated through a genome-wide association study (GWAS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: 18 - 45 years;
- •Sex: male and female;
- •Ethnicity: Chinese;
- •Good health as evidenced by the results of physical examination, vitals signs, electrocardiogram, and clinical laboratory test results, but there were exceptions if an abnormal value was considered not to be clinical significance;
- •Written informed consent.
排除标准
- •Any conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs;
- •Intolerance or hypersensitivity to drugs whose mechanism is similar to that of ticagrelor;
- •Any history of taking medicines within half a month before enrollment;
- •Any history of whole blood transfusion within 2 months, blood elements transfusion or blood donation within 1 months before enrollment;
- •Participation in a clinical study within 3 months before enrollment;
- •Abuse of caffeine (> 5 units/day), alcohol(> 21 units /week), smoking(> 10 cigarettes/day);
- •Positive serology for Hbs antigen and HIV;
- •History of coagulation disorders.
研究组 & 干预措施
Pharmacokinetics
The pharmacokinetics characteristic of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.
干预措施: Ticagrelor (Drug)
Antiplatelet effects
The antiplatelet effects of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Genome-wide genotyping in 51 healthy Chinese
时间窗: 10 weeks
A total of 900,015 SNPs in a GWAS scan were genotyped with the Illumina HumanOmniZhongHua-8 BeadChip according to the protocol from Illumina. Prior to association analysis, a systematic quality control (QC) procedure was applied to the raw genotyping data to filter unqualified SNPs and samples. The effects of genetic variants on antiplatelet and pharmacokinetic response to ticagrelor are investigated through a genome-wide association study（GWAS）in 51 healthy Chinese .
次要结局
- ADP-stimulated platelet aggregation(8 weeks)
- Peak plasma concentration (Cmax)(10 weeks)
- Time to peak plasma concentration (tmax)(10 weeks)
- Area under the plasma concentration-time curve (AUC)(10 weeks)
- Accumulated amount of ticagrelor and its metabolites in urine(10 weeks)
研究者
ShiLong Zhong
Professor
Guangdong Provincial People's Hospital