Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor

NCT03161002 | Unknown

• 1 other identifier: 2016[1235]
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 7

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.

Conditions

Ticagrelor; Pharmacokinetics; Pharmacodynamics; Pharmacogenomics; Accurate Medication

Outcome Measures

Primary Outcomes (2)

• Incidence of major adverse cardiac events (MACE)

  During the observation time, record the incidence of MACE after ticagrelor administration by telephone or outpatient clinic , including myocardial infarction, cardiac death, stent stenosis, stent thrombosis, ect.

  At 1 year

• Incidence of bleeding events

  During the observation time, record the incidence of bleeding events after ticagrelor administration by telephone or outpatient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.

  At 1 year

Secondary Outcomes (8)

• genotype detected by next generation sequencing

  pre-dose of Ticagrelor

• Level of platelet reactivity assessed by ADP aggregation rate

  At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.

• Level of platelet reactivity assessed by PRI

  At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.

• Expression level of miRNA

  At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.

• Expression level of proteomics

  At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients

Study Arms (2)

wild genotype

Through next generation sequencing, distinguish wild genotype of ticagrelor

Genetic: detection of genotype

mutant genotype

Through next generation sequencing, distinguish mutant genotype of ticagrelor

Genetic: detection of genotype

Interventions

detection of genotype GENETIC

detection of genotype by next generation sequencing

mutant genotype; wild genotype

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• (I)Chinese Healthy Volunteers
• 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.

You may not qualify if:

• (I)Chinese Healthy Volunteers
• (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.

Sponsors & Collaborators

• Cui Yimin: lead

Study Sites (7)

Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）

Hefei, Anhui, 230001, China

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230001, China

RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

RECRUITING

900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)

Fuzhou, Fujian, China

RECRUITING

The 7th People's Hospital Of Zhengzhou

Zhengzhou, Henan, 450006, China

ACTIVE NOT RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

ACTIVE NOT RECRUITING

The Second Affiliated Hospital Of Nanchang University

Nanchang, Jiangxi, 330006, China

ACTIVE NOT RECRUITING

Related Publications (2)

• 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.

  PMID: 35501592 DERIVED

• 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.

  PMID: 35082514 DERIVED

Central Study Contacts

Qian Xiang, Ph.D

CONTACT

+86 010 66110802; xiangqz@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of pharmacy，M.D & Ph.D

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 19, 2017
• Study Start: May 31, 2017
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2021
• Last Updated: December 22, 2020

Record last verified: 2020-12

Locations

CN (7)