Pharmacokinetics and Pharmacodynamics of Vicagrel in Healthy Adult Subjects of Different CYP2C19

NCT03942458 | Completed Phase 1

• 1 other identifier: VCP1-Ⅰ-04
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, randomized, open, two-cycle crossover, clopidogrel control, multiple dosing study. The aim was to evaluate the pharmacokinetic/pharmacodynamic behavior of different metabolites of CYP2C19 in healthy subjects. The study enrolled 48 patients, divided into three groups of CYP2C19 fast metabolite, middle metabolite, and slow metabolism, 16 cases in each group. All groups of subjects were administered for 7 days in the first cycle, once a day (loading dose on the first day, maintenance dose on other days), and entering the 14-day washout period after the end of the first cycle. The second cycle was entered, and the second cycle was administered for 7 days, once a day (the first day was given a loading dose, and the other days were given a maintenance dose). Blood was collected before and after administration of D1, D7, D22, and D28, and PK/PD was measured.

Conditions

Healthy Subjects; PK/PD

Outcome Measures

Primary Outcomes (5)

• Peak Plasma Concentration (Cmax)

  To evaluate the Peak Plasma Concentration (Cmax) after taking drugs

  1 day,7 days after taking drugs

• Area under the plasma concentration versus time curve (AUC)

  To evaluate the AUC after taking drugsl

  1 day,7 days after taking drugs

• Time to maximum plasma concentration （Tmax）

  To evaluate the Tmax after taking drugs

  1 day,7 days after taking drugs

• terminal half-life （T1/2）

  To evaluate the T1/2 after taking drugs

  1 day,7 days after taking drugs

• inhibition of platelet aggregation

  To evluate the inhibition of platelet aggregation assessed by Verifynow System after taking drugs

  1 day,7 days after taking drugs

Study Arms (2)

Vicagrel

EXPERIMENTAL

Vicagrel 24mg loading followed by 6mg/day for 6 days

Drug: Vicagrel 6mg

Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 300mg loading followed by 75mg/day for 6 days

Drug: Clopidogrel 75mg

Interventions

Vicagrel 6mg DRUG

Vicagrel 24mg loading followed by 6mg/day for 6 days

Vicagrel

Clopidogrel 75mg DRUG

Clopidogrel 300mg loading followed by 75mg/day for 6 days

Clopidogrel

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary signing of informed consent before the trial, and full understanding of the experimental content, process and possible adverse reactions;
• Subjects with ability and adherence to trial protocol;
• Subjects (including partners) voluntarily take effective contraceptive measures from screening to the last study drug administration within 6 months;
• Male and female aged 18-45,gender is unlimited (including 18 and 45 years old);
• Male Weight ≥50 kg, female Weight ≥ 45 kg, and BMI ranging from 18 to 28 kg/m2 (including critical values);
• Physical examination, normal or abnormal vital signs have no clinical significance (reference range of vital signs: systolic blood pressure 90-150 mmHg, diastolic blood pressure 50-95 mmHg, pulse 50-110 beats/min, body temperature 35.5-37.2 °C);
• CYP2C19 rapid metabolizers (CYP2C19\*1/\*1), or intermediate metabolizers (CYP2C19\*1/\*2, CYP2C19\*1/\*3), or poor metabolizers (CYP2C19\*2/\*2, CYP2C19\*2/\* 3, CYP2C19\*3/\*3).

You may not qualify if:

• More than 5 cigarettes per day 3 months before the trial;
• History of allergies or allergies to the drug (two or more drugs or food allergies);
• History of drug and/or alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine);
• Donate blood or massive blood loss (\> 450 mL) within 3 months prior to formal screening;
• Take any drug that alters the activity of CYP450s within 28 days before the formal screening;
• Take any prescription, non-prescription, any vitamin or herbal medicine within 14 days of the formal screening;
• Take special diet (including dragon fruit, mango, grapefruit, etc.) within 2 weeks before the formal screening, or have strenuous exercise, or other factors affecting drug absorption, distribution, metabolism, excretion, etc.;
• Taking inhibitors or inducers of the CYP3A4, P-gp or Bcrp Currently, such as itraconazole, ketoconazole or dronedarone;
• Recently there have been major changes in diet or exercise habits;
• Taking other research drugs or participating in clinical trials within 3 months before taking the study drug;
• History of dysphagia or any gastrointestinal disease affecting drug absorption;
• Have any disease that increases the risk of bleeding, such as acute gastritis, stomach and duodenal ulcers, thrombocytopenic purpura, hemophilia, and so on;
• ECG abnormalities have clinical significance;
• Female subjects are in lactation or have a positive of pregnancy test;
• Clinical laboratory abnormalities have clinical significance or other clinically significant abnormalities (including but not limited to gastrointestinal, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases);

Sponsors & Collaborators

• Jiangsu vcare pharmaceutical technology co., LTD: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Interventions

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

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 Design

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

Study Record Dates

• First Submitted: April 24, 2019
• First Posted: May 8, 2019
• Study Start: April 3, 2019
• Primary Completion: June 28, 2019
• Study Completion: September 3, 2019
• Last Updated: September 19, 2019

Record last verified: 2019-03

Locations

CN (1)