Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor

Pharmacokinetics Clinical Trial

Official title:

Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Ticagrelor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03161002
• Other study ID #: 2016[1235]
• Status: Recruiting
• Start date: May 31, 2017
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Peking University First Hospital
• Contact: Qian Xiang, Ph.D
• Phone: +86 010 66110802
• Email: xiangqz[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Accurate Medication
• Pharmacodynamics
• Pharmacogenomics
• Pharmacokinetics
• Ticagrelor

Intervention

Genetic:
• detection of genotype
detection of genotype by next generation sequencing

Locations

Country	Name	City	State
China	Peking University First Hospital	Beijing	Beijing
China	The Third Xiangya Hospital of Central South University	Changsha	Hunan
China	900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)	Fuzhou	Fujian
China	Anhui Provincial Hospital(The First Affiliated Hospital Of USTC)	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The Second Affiliated Hospital Of Nanchang University	Nanchang	Jiangxi
China	The 7th People's Hospital Of Zhengzhou	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Cui Yimin

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	genotype detected by next generation sequencing	Collect blood specimen before ticagrelor administration, then detect genotype of Ticagrelor by next generation sequencing.	pre-dose of Ticagrelor
Secondary	Level of platelet reactivity assessed by ADP aggregation rate	Before and after ticagrelor administration, record the ADP aggregation rate detected by Light Transmittance Aggregometry(LTA).	At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
Secondary	Level of platelet reactivity assessed by PRI	Before and after ticagrelor administration, record PRI detected by VerifyNow System.	At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
Secondary	Expression level of miRNA	Before and after ticagrelor administration, detect the expression level of miRNA about pharmacodynamics.	At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients.
Secondary	Expression level of proteomics	Before and after ticagrelor administration, detect the expression level of proteomics about pharmacodynamics	At baseline, at 12 hours for Chinese healthy volunteers or at 48 hours for Chinese patients
Secondary	Expression level of LncRNA	Before and after ticagrelor administration, detect the expression level of LncRNA about pharmacodynamics.	At baseline, at 12 hours for Chinese healthy volunteers;at 48 hours for Chinese patients.
Secondary	Incidence of MACEs in the other observation times	During the other 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 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens)
Secondary	Incidence of bleeding events in the other observation times	During the other 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 month, 6 months and 2 years (according the actual duration of ticagrelor taken in patiens)