PK/PD Study of Vicagrel and Clopidogrel in Healthy Subjects With Different CYP2C19 Metabolizers

A Phase 1, Open-label, Randomized, Multiple-dose, Crossover Pharmacokinetic/Pharmacodynamic Study of Vicagrel and Clopidogrel in Healthy Subjects With Different CYP2C19 Phenotypes

This clinical study will adopt an open-label, randomized, multiple-dose, two-crossover design to explore the pharmacokinetic and pharmacodynamic profiles of Vicagrel Capsules and Clopidogrel Tablets in Healthy Subjects with Different CYP2C19 Metabolizers

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • Phase I Clinical Research Center of The First Hospital of Jilin University
• United States
  • California
    • Los Angeles, California, United States, 90630
      • Altasciences Clinical, Los Angeles
  • Missouri
    • Kansas City, Missouri, United States, 66212
      • Altasciences, Kansas City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able and willing to give written informed consent before study, and fully understand the study content, process and possible adverse reactions;
2. Able to complete the study in compliance with the protocol;
3. Subject (including partner) is willing to voluntarily take effective contraceptive measures from screening through 90 days after the last dose of study drug (see Appendix 5 for details);
4. Male and female subjects between the ages of 18 and 65 years, inclusive;
5. At least 50 kg for male subjects, 45 kg for female subjects, with a Body Mass Index (BMI= Weight/Height2) between 18-32 kg/m2, inclusive;
6. With normal or clinically insignificant abnormal results of physical examination and vital signs test;
7. Subjects will be assigned into the group according to the CYP2C19 genotype: the first group of ultra-rapid metabolizers (CYP2C19*17/*17); the second group of rapid metabolizers (CYP2C19*1/*17); the third group of normal metabolizers (CYP2C19*1/*1); the fourth group of intermediate metabolizers (CYP2C19*1/*2, *1/*3, *2/*17, *3/*17); and the fifth group of poor metabolizers (CYP2C19*2/*2, *2/*3, *3/*3).。

Exclusion Criteria:

1. More than 5 cigarettes per day on average within 3 months before the study;
2. History of sensitivity to drugs similar to the study drug or have high sensitivity to clopidogrel, allergic constitution (e.g. allergy to various drugs and foods);
3. History of drug abuse, drug use, alcohol abuse (14 units of alcohol per week: 1 units = 285 mL beer, 25 mL spirit or 100 mL wines);
4. Donation or loss of a significant volume of blood (> 450 mL) within 56 days prior to screening;
5. Intake of any prescription drugs, over-the-counter drugs, vitamin or herbal medicine within 14 days prior to receiving study drug;
6. Consumption of any special diet (such as grapefruit, pitaya, mango, pomelo, etc.) or subjects have engaged strenuous exercise or any other factors affecting drug absorption, distribution, metabolism and excretion within 14 days prior to receiving study drug;
7. Intake of any drug which Have taken strong inhibitors and/or inducers of liver metabolic enzymes (CYP1A2, 2A6, 2C8, 2C19, 3A4 and 3A5) within 28 days before the first medication, and strong inhibitors of liver metabolic enzymes such as: ciprofloxacin, clopidogrel, Itraconazole, ketoconazole, ritonavir, troleandomycin, etc., strong inducers of liver metabolism enzymes such as: rifampicin, carbamazepine, phenytoin sodium, St. John's wort, etc.(For details see Appendix 6);
8. Recent major changes in diet or exercise habits;
9. Use of an investigational drug or product, or participation in a drug research study within 30 days (or 5 half-lives) prior to receiving study drug;
10. History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption;
11. Suffering from any diseases that may increase the risk of bleeding, such as hemorrhoids, acute gastritis, stomach and duodenal ulcers, Thrombocytopenic Purpura and hemophilia, etc;
12. Family history of coagulation or bleeding disorders (e.g., hemophilia)/symptoms (e.g., vomiting blood, black stools, severe or recurrent nosebleeds, coughing up blood, significant hematuria, or intracranial hemorrhage) or suspected vascular malformations, such as aneurysms or early onset strokes, in the individual or in their immediate family;
13. A clinically significant 12-lead ECG abnormality;
14. Positive test results of blood pregnancy or subject is lactating for female subjects;
15. Any clinically significant abnormalities/findings in laboratory tests, or any clinically significant disease including but not limited to gastrointestinal, renal, hepatic, neurological system, blood, endocrine, tumor, lung, immune, mental, or cardiovascular and cerebrovascular diseases;
16. Positive test results for viral hepatitis (including hepatitis B and C), HIV antibody or syphilis antibody;
17. Acute illness or concomitant medication from screening to the first dosing of study medication;
18. Consumption of chocolate or any food or beverages containing caffeine or (rich containing) xanthine within 48 h prior to receiving the first dosing of study medication;
19. Consumption of any product containing alcohol within 24 h prior to receiving the first dosing of study medication, or positive results from a screen for alcohol;
20. Positive results from a screen for urine drug test (Morphine, marijuana);
21. Subjects were vaccinated within 4 weeks prior to screening, or planned to be vaccinated during the trial;
22. Any condition which in the opinion of Investigator is not suitable for subjects to participate in the study (For ultra-rapid metabolizers and rapid metabolizers, investigators may consider at their discretion).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultra-rapid metabolizers group; A 7-day cross-dosing of vicagrel and clopidogrel between two cycles	Drug: vicagrel Capsules; Oral administration for 7 days under fasting; Drug: Clopidogrel Tablets; Oral administration for 7 days under fasting; Other Names: PLAVIX
Experimental: Rapid metabolizers group; A 7-day cross-dosing of vicagrel and clopidogrel between two cycles	Drug: vicagrel Capsules; Oral administration for 7 days under fasting; Drug: Clopidogrel Tablets; Oral administration for 7 days under fasting; Other Names: PLAVIX
Experimental: Normal metabolizers group; A 7-day cross-dosing of vicagrel and clopidogrel between two cycles	Drug: vicagrel Capsules; Oral administration for 7 days under fasting; Drug: Clopidogrel Tablets; Oral administration for 7 days under fasting; Other Names: PLAVIX
Experimental: Intermediate metabolizers group; A 7-day cross-dosing of vicagrel and clopidogrel between two cycles	Drug: vicagrel Capsules; Oral administration for 7 days under fasting; Drug: Clopidogrel Tablets; Oral administration for 7 days under fasting; Other Names: PLAVIX
Experimental: Poor metabolizers group; A 7-day cross-dosing of vicagrel and clopidogrel between two cycles	Drug: vicagrel Capsules; Oral administration for 7 days under fasting; Drug: Clopidogrel Tablets; Oral administration for 7 days under fasting; Other Names: PLAVIX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inhibition of platelet aggregation [IPA] evaluated in healthy subjects to treatment with either vicagrel or clopidogrel	To compare IPA following multiple doses of vicagrel and/or clopidogrel in healthy subjects with different CYP2C19 phenotypes.	Day1-Day31
Platelet reactivity index [PRI] evaluated in healthy subjects to treatment with either vicagrel or clopidogrel	To compare PRI following multiple doses of vicagrel and/or clopidogrel in healthy subjects with different CYP2C19 phenotypes.	Day1-Day31
maximum plasma concentration (Cmax)	To compare Cmax following multiple doses of vicagrel and/or clopidogrel in healthy subjects with different CYP2C19 phenotypes.	Day1-Day31
Area under the curve over a dosing interval(AUC0-tau)	To compare AUC0-tau following multiple doses of vicagrel and/or clopidogrel in healthy subjects with different CYP2C19 phenotypes.	Day1-Day31

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the safety and tolerability of multiple doses of both drugs in each CYP2C19 phenotype group.	Day1-Day31

Collaborators and Investigators

• Sponsor: Jiangsu vcare pharmaceutical technology co., LTD
• Investigators: Principal Investigator: Yanhua Ding, Phase I Clinical Research Center of The First Hospital of Jilin University; Principal Investigator: Youngjun David Kim, MD, Altasciences Clinical, Los Angeles; Principal Investigator: Martin Kankam, MD, Altasciences, Kansas City

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Actual): November 3, 2022
• Study Completion (Actual): November 3, 2022

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: VCP1-Ⅰ-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No