The Impact of Genotype on Pharmacokinetics and Antiplatelet Effects of Ticagrelor in Healthy Chinese (IGPPT)

Guangdong Provincial People's Hospital (Guangdong Provincial Academy of Medical Sciences)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Ticagrelor

Study type: Interventional

Funder types: Other

Identifiers

NCT03092076

GDREC2015143H(R1)

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 51 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age: 18 - 45 years;
2. Sex: male and female;
3. Ethnicity: Chinese;
4. 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;
5. Written informed consent.

Exclusion criteria

1. Any conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs;
2. Intolerance or hypersensitivity to drugs whose mechanism is similar to that of ticagrelor;
3. Any history of taking medicines within half a month before enrollment;
4. Any history of whole blood transfusion within 2 months, blood elements transfusion or blood donation within 1 months before enrollment;
5. Participation in a clinical study within 3 months before enrollment;
6. Abuse of caffeine (> 5 units/day), alcohol(> 21 units /week), smoking(> 10 cigarettes/day);
7. Positive serology for Hbs antigen and HIV;
8. History of coagulation disorders.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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51 participants in 3 patient groups

Pharmacokinetics

Experimental group

Description:

The pharmacokinetics characteristic of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.

Treatment:

Drug: Ticagrelor

Antiplatelet effects

Experimental group

Description:

The antiplatelet effects of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.

Treatment:

Drug: Ticagrelor

The impact of genotype

No Intervention group

Description:

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.