Clinical trial NCT03161002: Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor
Official title: Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Ticagrelor
Pharmacokinetics
Pharmacodynamics
Pharmacogenomics
Accurate Medication
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2017-05-19
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: (I)Chinese Healthy Volunteers：In accordance with the criteria of each bioequivalence trial of ticagrelor；150-200 cases (II)Chinese Patients：With diagnosis of acute coronary syndrome (ACS)，never received ticagrelor in a month and intend to take ticagrelor or have received ticagrelor for more than one week continuously；200 cases

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of major adverse cardiac events (MACE)
timeFrame: At 1 year
measure: Incidence of bleeding events
timeFrame: At 1 year
Secondary outcomes:
measure: genotype detected by next generation sequencing
timeFrame: pre-dose of Ticagrelor
measure: Level of platelet reactivity assessed by ADP aggregation rate
timeFrame: At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
measure: Level of platelet reactivity assessed by PRI
timeFrame: At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
measure: Expression level of miRNA
timeFrame: At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
measure: Expression level of proteomics
timeFrame: At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients
measure: Expression level of LncRNA
timeFrame: At baseline, at 12 hours for Chinese healthy volunteers；at 48 hours for Chinese patients.
measure: Incidence of MACEs in the other observation times
timeFrame: At 1 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens)
measure: Incidence of bleeding events in the other observation times
timeFrame: At 1 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Fuzhou
country: China
facility: 900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)
state: Fujian
city: Zhengzhou
country: China
facility: The 7th People's Hospital Of Zhengzhou
state: Henan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Nanchang
country: China
facility: The Second Affiliated Hospital Of Nanchang University
state: Jiangxi
Study officials:
References:
citation: Xiang Q, Liu Z, Mu G, Xie Q, Zhang H, Zhou S, Wang Z, Guo N, Huang J, Jiang J, Li J, Yang G, Cui Y. Effect of Genetic Polymorphism Including NUP153 and SVEP1 on the Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects. Clin Drug Investig. 2022 May;42(5):447-458. doi: 10.1007/s40261-022-01154-6. Epub 2022 Apr 30.
citation: Yuan D, Shi X, Gao L, Wan G, Zhang H, Yang Y, Zhao Y, Sun D. Identification of Potential Biological Factors Affecting the Treatment of Ticagrelor After Percutaneous Coronary Intervention in the Chinese Population. Pharmgenomics Pers Med. 2022 Jan 20;15:29-43. doi: 10.2147/PGPM.S338287. eCollection 2022.