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Completed

NCT Number: NCT03092076

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

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.

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Key information

Conditions

Healthy

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

Ticagrelor

Drug

180 mg loading dose

Other names: Brilinta, AstraZeneca

Primary outcomes

  1. Genome-wide genotyping in 51 healthy Chinese

    Time frame: 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 .

Secondary outcomes

  1. ADP-stimulated platelet aggregation

    Time frame: 8 weeks

    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.

  2. Peak plasma concentration (Cmax)

    Time frame: 10 weeks

    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.

  3. Time to peak plasma concentration (tmax)

    Time frame: 10 weeks

    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.

  4. Area under the plasma concentration-time curve (AUC)

    Time frame: 10 weeks

    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.

  5. Accumulated amount of ticagrelor and its metabolites in urine

    Time frame: 10 weeks

    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).

Sponsors and collaborators

Lead sponsor

Guangdong Provincial People's Hospital

Other

Registry information

Acronym: IGPPT

Important dates

Study start
2015
Primary completion
2015
Study completion
2016
First posted
Mar 27, 2017
Registry last updated
Mar 27, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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