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.

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.