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

March 21, 2017 updated by: ShiLong Zhong, Guangdong Provincial People's Hospital
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pharmacokinetics
The pharmacokinetics characteristic of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.
Drug: Ticagrelor
180 mg loading dose
Other Names:
  • Brilinta
  • AstraZeneca
Experimental: Antiplatelet effects
The antiplatelet effects of ticagrelor in healthy Chinese is investigated to provide the basis for its efficacy and safety of clinical treatment.
Drug: Ticagrelor
180 mg loading dose
Other Names:
  • Brilinta
  • AstraZeneca
No Intervention: The impact of genotype
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 .
10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
8 weeks
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.
10 weeks
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.
10 weeks
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.
10 weeks
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).
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangdong Provincial People's Hospital

Investigators

  • Principal Investigator: Shilong Zhong, Ph.D, Guangdong Provincial People's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 20, 2015

Primary Completion (Actual)

October 24, 2015

Study Completion (Actual)

June 16, 2016

Study Registration Dates

First Submitted

March 9, 2017

First Submitted That Met QC Criteria

March 21, 2017

First Posted (Actual)

March 27, 2017

Study Record Updates

Last Update Posted (Actual)

March 27, 2017

Last Update Submitted That Met QC Criteria

March 21, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GDREC2015143H(R1)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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