The Pharmacokinetics and Pharmacodynamics Study of Evategrel CG-0255 Besylate）and Plavix® in Healthy Participants

A Pivotal Comparative Pharmacokinetics (PK) and Pharmacodynamics (PD) Study of CG-0255 Besylate and Plavix® in Healthy Participants

CG-0255 is a novel investigational prodrug of the active metabolite of Plavix®， but with different active metabolite conversion routes. This is a randomized, open-label and Plavix®-controlled study to compare the PK and PD of CG-0255 Besylate and Plavix® in healthy participants.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Arterial Disease; Recent Myocardial Infarction; Acute Coronary Syndromes (ACS); Recent Stroke
• Intervention / Treatment: Drug: CG-0255 Besylate Capsule; Drug: CG-0255 Besylate for Injection; Drug: Clopidogrel

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Isabel Pino; Phone Number: 305-547-5813; Email: Isabel.pino@syneoshealth.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33101
      • Recruiting
      • Syneos Health
      • Contact: Isabel Pino; Phone Number: 305-547-5813; Email: Isabel.pino@syneoshealth.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants must be fully informed about the study, willing to participate, and sign the informed consent document prior to any procedure.
• Healthy male and female participants, aged 18 to 55 years (inclusive) at time of signing informed consent form.
• Body mass index (BMI) between 18 and 32 kg/m2 (inclusive) at screening and body weight between 45 and 120 kg (inclusive).
• Smoking < 10 cigarettes (10-20 mg of nicotine/month) or equivalent amount of nicotine products per month within 6 months prior to screening and agree to abstain from tobacco and/or nicotine products during the study.
• Generally normal health, or abnormalities deemed non-clinically significant by the Investigator or designee based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests at the screening and at the admission.

• For female participants,

  1. Woman of child-bearing potential (WOCBP) must be non-pregnant and non-lactating, and must agree to use highly effective contraceptive methods and abstain from egg collection or donation from the screening period to 3 months after the last dose of the study treatment (CG-0255 Besylate or Plavix®). The male partner of a female participant also needs to use condoms during this period.
  2. Woman of non-childbearing potential (WONCBP) must be post menopausal (spontaneous amenorrhea for at least 12 consecutive months prior to dosing) with confirmation by documented FSH levels ≥40 mIU/mL; or surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, or bilateral tubal ligation) at least 3 months prior to dosing.
• Male participants considered fertile must agree to not plan to father a child, not donate sperm and take effective contraceptive methods from the screening period to 3 months after the last dose of the study treatment. The female partner of a male participant also needs to use a highly effective contraceptive method during this period.
• Male participants (including men who have had a vasectomy) with a pregnant partner must agree to use a condom from the screening period to 3 months after the last dose of the study treatment.
• Participants must be able to communicate well with the Investigator or designee, as well as understand and adhere to the study's requirements.

Exclusion Criteria:

• Difficulty with venous blood collection or a history of fainting upon seeing blood or needles.
• Clinically relevant drug intolerance or allergy or known or suspected hypersensitivity to any component of CG-0255 Besylate or Plavix®, or other related drugs.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or 5 times half-life, whichever is longer) prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days (or 5 times half-life, whichever is longer) prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Current or unresolved digestive tract diseases (dyspepsia, gastroesophageal reflux, gastro-hemorrhage, or digestive tract ulcer disease) within the past 6 months, or frequent (> 1 time/week) digestive tract symptoms including dysphagia, abdominal pain, abdominal distension, acid regurgitation, belching, hematemesis, bloody stool, anorexia, nausea, heartburn, and other symptoms that may increase the risk of bleeding, as determined by the Investigator or designee.
• Any clinically significant diseases including but not limited to pulmonary, cardiovascular, gastrointestinal, hematological, endocrinological, immunological, dermatological, malignant diseases, mental and nervous systems, and other related diseases or any other condition at the discretion of the Investigator or designee.
• History of previous or current active bleeding (such as intracranial hemorrhage, gastrointestinal hemorrhage, urethral hemorrhage, hemoptysis, vitreous hemorrhage, bleeding caused by stool and hemorrhoids), transient ischemic attack or stroke, abnormal bleeding (such as prolonged bleeding time after tooth extraction), presence of petechiae and/or ecchymosis on physical examination, or suspected vascular malformations (such as aneurysms or early-onset stroke, not exceeding the age limit specified in the inclusion criteria).
• Hemoglobin <120 g/L for males and <110 g/L for females at screening.
• Medication history of NSAIDs (including Aspirin) or other drugs that may affect coagulation function (e.g, oral anticoagulants) within 4 weeks before the screening.
• Platelet count < 120 × 10^9/L at screening.
• Laboratory measures with values above the 1.5 × upper limits of normal (ULN) and deemed clinically significant by the Investigator or designee for the alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST).
• Clinically significant ECG abnormalities (QTcF interval ≥ 450 ms for male, ≥ 470 ms for female (Fridericia's Correction)) or vital signs abnormalities (systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 50 or over 90mmHg, HR less than 50 or over 100 bpm, or RR less than 10 or over 22 bpm) at screening.
• Major surgery within 3 months prior to the first dose of study treatment or plans for surgery during the study.
• Use of prescription, nonprescription or dietary supplements (e.g. food supplements and herbal supplements) within 14 days or 5 times the half life (whichever is longer) prior to the first dose of study treatment (excluding drug products without significant systemic absorption at the discretion of the Investigator or designee), or depot injection or implant within 3 months prior to first dosing, with the exception of the occasional use of acetaminophen (up to 2 g daily).
• Vaccinated within 14 days prior to the first dose of study treatment or planned to be vaccinated during the study.
• Consuming quinine containing products, including quinine water, tonic water bitter lemon, jello shots, any quinine preparations or Cinchona tree bark reparations (e.g., herbal medications containing Cinchona tree bark), and grapefruit or products containing grapefruit, or participants have engaged strenuous exercise or any other factors affecting drug absorption, distribution, metabolism and excretion within 7 days before the first dose of study treatment.
• History of drug abuse within 1 year before screening, or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
• Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or at the admission.
• Positive pregnancy test or lactating female participant at screening or at the admission.
• Donation of plasma within 7 days prior to the first dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to the first dosing.
• History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5%, 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
• Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Excessive drinking of tea, coffee, or caffeine-containing beverage (>600 mg/day) within 30 days before screening; intake of caffeine- or xanthine rich foods or drinks (e.g., coffee, tea, chocolate, cola drinks) within 48 hours prior to the first dose of study treatment, which may metabolize into caffeine or xanthine.
• Positive screening for human immunodeficiency virus (HIV) antigen and antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening.
• Estimated glomerular filtration rate (eGFR) <60 mL/min as calculated per CKD-EPI equation, at screening.
• Use of any drugs known to induce or inhibit hepatic drug metabolism (including CYP2C19 inducers or inhibitors) within 30 days prior to the first study drug administration or 5 half-lives (whichever is longer) until the end of the study.
• Participants deemed ineligible to participate in this study by the Investigator or designee.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: CG-0255 oral for both Loading Dose (LD) and Maintenance Dose (MD); For Treatment A, participants will be administered with 3 mg CG-0255 Besylate capsules on Day 1. Subsequently, they will receive 0.75 mg CG-0255 Besylate capsules once daily from Days 2 to 7.	Drug: CG-0255 Besylate Capsule; Orally administered as LD or MD with approximately 240 mL of water.
Experimental: Treatment B: CG-0255 iv for LD and oral for MD; For Treatment B, participants will be administered with 0.05 mg/kg CG-0255 Besylate for IV infusion within 30 minutes on Day 1. Subsequently, they will receive 0.75 mg CG-0255 Besylate capsules once daily from Days 2 to 7.	Drug: CG-0255 Besylate Capsule; Orally administered as LD or MD with approximately 240 mL of water.; Drug: CG-0255 Besylate for Injection; Calculate the dosage and number of vials required for a participant according to body weight. Reconstitute with 5 mL of sterile water for each 5 mg/vial to get clear solution for injection in 1 mg/mL (as CG-0255). The reconstituted CG-0255 Besylate for injection (1 mg/mL), must be further diluted in 100 mL normal saline infusion bag, following the instruction in the pharmacy manual.
Active Comparator: Treatment C: Plavix® 300mg for LD and 75mg for MD; For Treatment C, participants will be administered with 300 mg Plavix® on Day 1 as 4 x 75 mg Plavix® tablets. Subsequently, they will receive 75 mg Plavix® once daily from Days 2 to 7.	Drug: Clopidogrel; Orally administered as LD or MD with approximately 240 mL of water.
Active Comparator: Treatment D: Plavix® 600mg for LD and 75mg for MD; For Treatment D, participants will be administered with 600 mg Plavix® on Day 1 as 8 x 75 mg Plavix® tablets. Subsequently, they will receive 75 mg Plavix® once daily from Days 2 to 7.	Drug: Clopidogrel; Orally administered as LD or MD with approximately 240 mL of water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the PK of the active metabolite CG-0236 of CG-0255 Besylate and of Plavix® when they are administered as loading dose (LD) and maintenance dose (MD) in healthy participants.	Area under the plasma concentration-time curve from time 0 to the last quantifiable measurement time-point (AUClast)	Day 1 (LD) and Day 7 (MD)
To compare the PK of the active metabolite CG-0236 of CG-0255 Besylate and of Plavix® when they are administered as loading dose (LD) and maintenance dose (MD) in healthy participants.	Peak Plasma Concentration (Cmax)	Day 1 (LD) and Day 7 (MD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the PD of the active metabolite CG-0236 of CG-0255 Besylate and of Plavix® when administered as LD and MD in healthy participants.	The inhibition of platelet reactivity unit (PRU) based on VerifyNow assay, the inhibition of maximum platelet aggregation (MPA) based on Light Transmittance Aggregometry (LTA) assay.	Day 1 (LD) and Day 7 (MD)
To evaluate the Cmax of CG-0255 when administered CG-0255 Besylate as LD and MD in healthy participants.	Peak Plasma Concentration (Cmax)	Day 1 (LD) and Day 7 (MD)
To evaluate the safety and tolerability of CG-0255 Besylate and Plavix® when administered as LD and MD in healthy participants.	Number of Participants with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment.	Day 1-13
To evaluate the AUC of CG-0255 when administered CG-0255 Besylate as LD and MD in healthy participants.	Area under the plasma concentration-time curve from time 0 to the last quantifiable measurement time-point (AUClast)	Day 1 (LD) and Day 7 (MD)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore the effect of CYP2C19 genetic polymorphism on the PK of CG-0236 following CG-0255 Besylate and Plavix® administration.	Comparisons of plasma AUC of CG-0236 stratified by CYP2C19 genotypes: normal, intermediate and poor metabolizers	Day 1 (LD) and Day 7 (MD)
To explore the effect of CYP2C19 genetic polymorphism on the PD following CG-0255 Besylate and Plavix® administration.	Comparison of platelet reactivity unit (PRU) and/or maximal platelet aggregation (MPA) inhibition stratified by CYP2C19 genotypes: normal, intermediate and poor metabolizers.	Day 1 (LD) and Day 7 (MD)
To explore the effect of CYP2C19 genetic polymorphism on the PK of CG-0236 following CG-0255 Besylate and Plavix® administration.	Comparisons of plasma Cmax of CG-0236 stratified by CYP2C19 genotypes: normal, intermediate and poor metabolizers.	Day 1 (LD) and Day 7 (MD)

Collaborators and Investigators

• Sponsor: Shanghai CureGene Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 29, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Myocardial Ischemia; Peripheral Arterial Disease; Acute Coronary Syndrome; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Administration Routes; Drug Therapy; Thiophenes; Ticlopidine; Thienopyridines; Clopidogrel; Injections
• Other Study ID Numbers: Shanghai CureGene Pharmaceutic

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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