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

NCT05162053 | Completed Phase 1 FDA Drug

• 1 other identifier: VCP1-Ⅰ-06
• Study Type: interventional
• Target: 128
• Locations: 2 countries
• Sites: 3

Brief Summary

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

Conditions

Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (1)

• Assess the safety and tolerability of multiple doses of both drugs in each CYP2C19 phenotype group.

  Day1-Day31

Study Arms (5)

Ultra-rapid metabolizers group

EXPERIMENTAL

A 7-day cross-dosing of vicagrel and clopidogrel between two cycles

Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

Rapid metabolizers group

EXPERIMENTAL

A 7-day cross-dosing of vicagrel and clopidogrel between two cycles

Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

Normal metabolizers group

EXPERIMENTAL

A 7-day cross-dosing of vicagrel and clopidogrel between two cycles

Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

Intermediate metabolizers group

EXPERIMENTAL

A 7-day cross-dosing of vicagrel and clopidogrel between two cycles

Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

Poor metabolizers group

EXPERIMENTAL

A 7-day cross-dosing of vicagrel and clopidogrel between two cycles

Drug: vicagrel Capsules; Drug: Clopidogrel Tablets

Interventions

vicagrel Capsules DRUG

Oral administration for 7 days under fasting

Intermediate metabolizers group; Normal metabolizers group; Poor metabolizers group; Rapid metabolizers group; Ultra-rapid metabolizers group

Clopidogrel Tablets DRUG

Oral administration for 7 days under fasting

Also known as: PLAVIX

Intermediate metabolizers group; Normal metabolizers group; Poor metabolizers group; Rapid metabolizers group; Ultra-rapid metabolizers group

Eligibility Criteria

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

You may qualify if:

• Able and willing to give written informed consent before study, and fully understand the study content, process and possible adverse reactions;
• Able to complete the study in compliance with the protocol;
• 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);
• Male and female subjects between the ages of 18 and 65 years, inclusive;
• 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;
• With normal or clinically insignificant abnormal results of physical examination and vital signs test;
• 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).。

You may not qualify if:

• More than 5 cigarettes per day on average within 3 months before the study;
• 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);
• 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);
• Donation or loss of a significant volume of blood (\> 450 mL) within 56 days prior to screening;
• Intake of any prescription drugs, over-the-counter drugs, vitamin or herbal medicine within 14 days prior to receiving study drug;
• 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;
• 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);
• Recent major changes in diet or exercise habits;
• 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;
• History of difficulties in swallowing, or any gastrointestinal disease which could affect the drug absorption;
• 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;
• 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;
• A clinically significant 12-lead ECG abnormality;
• Positive test results of blood pregnancy or subject is lactating for female subjects;
• 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;

Sponsors & Collaborators

• Jiangsu vcare pharmaceutical technology co., LTD: lead

Study Sites (3)

Altasciences Clinical, Los Angeles

Los Angeles, California, 90630, United States

Location

Altasciences, Kansas City

Kansas City, Missouri, 66212, United States

Location

Phase I Clinical Research Center of The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

methyl 2-(2-acetoxy-6,7-dihydrothieno(3,2-c)pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multiple-center, open-label, randomized, multiple-dose, crossover design

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: December 17, 2021
• Study Start: December 9, 2021
• Primary Completion: November 3, 2022
• Study Completion: November 3, 2022
• Last Updated: November 3, 2023

Record last verified: 2023-11

Locations

US (2); CN (1)