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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pharmacokinetics | Experimental | The pharmacokinetics characteristic of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment. |
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| Antiplatelet effects | Experimental | The antiplatelet effects of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment. |
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| The impact of genotype | No Intervention | The recovery time of platelet function following the administration of ticagrelor is widely varied that genetic variants maybe an underlying factor.The impact of genotype on pharmacokinetic parameters and ADP of ticagrelor is compared among different genotypes. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor | Drug | 180 mg loading dose |
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| Measure | Description | Time Frame |
|---|---|---|
| Genome-wide genotyping in 51 healthy Chinese | 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 . | 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| ADP-stimulated platelet aggregation | For platelet function tests, ADP-stimulated platelet aggregation was measured in ethylenediaminetetraacetic acid (EDTA) anticoagulated whole blood samples (2 x 2 mL) within 2 h of sampling using a Chrono-log Platelet Aggregation Systems. The platelet aggregation (PA) postdose till recovery to baseline was measured by light transmission method using ADP (20 μmol/L final concentration), and expressed as percentages. Since a sparse sampling design for platelet function testing was used, the missing platelet aggregation data during the recovery of platelet function were imputed using Bayesian simulation method. The time recovering 50% of maximum drug effect (RT50) were estimated individually, which were used to represent the antiplatelet effect. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shilong Zhong, Ph.D | Guangdong Provincial People's Hospital | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40682019 | Derived | Chen J, Xu G, Xie Z, Xie S, Luo W, Zhong S, Lai W. GPD2 inhibition impairs coagulation function via ROS/NF-kappaB/P2Y12 pathway. Cell Mol Biol Lett. 2025 Jul 18;30(1):84. doi: 10.1186/s11658-025-00759-x. | |
| 35574651 | Derived | Xu G, Liu JE, Liu X, Zhong W, Wang Z, Li H, Xiao X, Chen J, Zhong S, Lai W. DNA methylation mediates the genetic variants on ticagrelor major metabolite elimination and platelet function recovery after ticagrelor discontinuation. Epigenomics. 2022 May;14(10):601-613. doi: 10.2217/epi-2021-0461. Epub 2022 May 16. |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| D000090985 | ChAdOx1 nCoV-19 |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| 8 weeks |
| Peak plasma concentration (Cmax) | A LC-MS/MS assay was developed and validated for simultaneous determination of ticagrelor, its metabolites, and internal standard (ferulic acid) in human plasma. Plasma samples were extracted with ethyl acetate. Peak plasma concentration (Cmax) of ticagrelor and M8 were estimated for each subject, using the non-compartmental analysis function in Phoenix WinNonlin software, version 6.3. | 10 weeks |
| Time to peak plasma concentration (tmax) | A LC-MS/MS assay was developed and validated for simultaneous determination of ticagrelor, its metabolites, and internal standard (ferulic acid) in human plasma. Plasma samples were extracted with ethyl acetate. Time to peak plasma concentration (tmax) of ticagrelor and M8 were estimated for each subject, using the non-compartmental analysis function in Phoenix WinNonlin software, version 6.3. | 10 weeks |
| Area under the plasma concentration-time curve (AUC) | A LC-MS/MS assay was developed and validated for simultaneous determination of ticagrelor, its metabolites, and internal standard (ferulic acid) in human plasma. Plasma samples were extracted with ethyl acetate. Area under the plasma concentration-time curve (AUC) of ticagrelor and M8 were estimated for each subject, using the non-compartmental analysis function in Phoenix WinNonlin software, version 6.3. | 10 weeks |
| Accumulated amount of ticagrelor and its metabolites in urine | A LC-MS/MS assay was developed and validated for simultaneous determination of ticagrelor, its metabolites, and internal standard (gliclazide) in human urine. Urine samples were precipitated with 50% methanol/acetonitrile. Accumulated amount of ticagrelor and its metabolites in urine over 24 h was calculated. The relative accumulated amount was the product of the relative index and the urine volume (Compound/IS x Vurine). | 10 weeks |
| 30936830 | Derived | Zhu Q, Zhong W, Wang X, Mai L, He G, Chen J, Tang L, Liu S, Lai W, Zhong S. Pharmacokinetic and Pharmacogenetic Factors Contributing to Platelet Function Recovery After Single Dose of Ticagrelor in Healthy Subjects. Front Pharmacol. 2019 Mar 18;10:209. doi: 10.3389/fphar.2019.00209. eCollection 2019. |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D019444 | Vaccines, DNA |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |