Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor

Cui Yimin

Status

Unknown

Conditions

Pharmacodynamics

Ticagrelor

Pharmacogenomics

Accurate Medication

Pharmacokinetics

Treatments

Genetic: detection of genotype

Study type

Observational

Funder types

Other

Identifiers

NCT03161002

2016[1235]

Details and patient eligibility

About

It is general that there are many factors for individual differences of drugs in clinical application, of which genetic factors accounted for more than 20%. Ticagrelor is a new-type receptor antagonist of P2Y12 and it is not affected by the influence of CYP2C19 polymorphism. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of ticagrelor in the antiplatelet efficacy and safety, through the pharmacogenomics research.

The aim of this study is to determine the polymorphism of drug metabolizing enzymes, drug transporters and drug target genes in Chinese population. By detecting the gene polymorphism, we intend to study the pharmacokinetic/ pharmacodynamics/ pharmacogenomics (PK-PD-PG) correlation of ticagrelor and provide scientific basis for accurate medication guide for people to use ticagrelor.

Enrollment

400 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

(I)Chinese Healthy Volunteers

In accordance with the inclusion criteria for each bioequivalence trial of ticagrelor;
Sign informed consent of the research;
Complete to collect indexes of pharmacodynamics and pharmacogenomics in the cycle with control drug.

(II)Chinese Patients

With diagnosis of acute coronary syndrome (ACS), included unstable angina, non ST segment elevation myocardial infarction and ST segment elevation myocardial infarction;
More than 18 years of age, male or female;
Never received ticagrelor in a month and intend to take ticagrelor or have received ticagrelor for more than one week continuously；
sign informed consent.

Exclusion criteria

(I)Chinese Healthy Volunteers

In accordance with the exclusion criteria for each bioequivalence trial of ticagrelor;

(II)Chinese Patients

With history of immunodeficiency disease, including positive HIV index;
Positive Hepatitis B surface antigen (HBsAg) and HCV index;
Combined therapy of CYP3A potent inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, Atazanavir, etc.), CYP3A substrate of narrow therapy window (e.g., cyclosporine, quinidine, etc.) and potent inducers of CYP3A (e.g., rifampin, phenytoin, carbamazepine, etc.) in 14 days before treatment with ticagrelor;
Severe liver dysfunction and abnormal renal function;
Uncontrolled hypertension, or systolic blood pressure > 180mmHg or diastolic pressure > 110mmHg during screening;
Include contraindications of ticagrelor, such as hypersensitivity, active bleeding, moderate or severe liver disease, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days.