Pharmacokinetic Effect of Y-3 for Injection on Rosuvastatin Calcium Tablets in Healthy Participants

A Single-center, Open-label, Single-arm, Fixed-sequence, Self-controlled Study to Evaluate the Pharmacokinetic Effect of Y-3 for Injection on Rosuvastatin Calcium Tablets in Healthy Participants

The primary objective of this study is to evaluate the effect of Y-3 for injection on the pharmacokinetics of rosuvastatin calcium tablets (a sensitive BCRP probe substrate) in healthy participants, in order to assess the potential clinical drug-drug interaction. The results will inform the drafting of the Y-3 for injection package insert and support its safe and rational post-marketing use.

The secondary objectives is to evaluate the effect of Y-3 for injection on the safety of rosuvastatin calcium tablets, and to evaluate the effect of rosuvastatin calcium tablets on the pharmacokinetics of Y-3 for injection in healthy participants.

This study is a single-center, open-label, single-arm, fixed-sequence, self-controlled study. A total of at least 20 participants (about half men and half women) will be will be enrolled and needed to complete in the study.On Days 1 and 11 of the trial, subjects shall orally take one tablet (10 mg) of rosuvastatin calcium on an fasted in the morning.From Day 5 to Day 14, 40 mg of Y-3 for Injection shall be administered via intravenous infusion once daily in the morning for 10 consecutive days (with an infusion duration of approximately 60 minutes). On Day 11, Y-3 for Injection (40mg) and one tablet (10mg) of rosuvastatin calcium shall be co-administered simultaneously.(with an interval of no more than 1 minute between the two administrations).

Inclusion Criteria:

1. Participants fully understand the purpose, nature, methods and possible adverse reactions of the trial, voluntarily act as participants, and sign the informed consent form before the start of any study procedures;
2. Healthy male or female participants aged 18 ~ 50 years old (inclusive);
3. Male weight ≥ 50.0 kg, female weight ≥ 45.0 kg, Body Mass Index from19.0 to 26.0 kg/m2(inclusive).
4. The results of vital signs, physical examination, 12-lead electrocardiogram examination, abdominal B-ultrasound (liver, gallbladder, pancreas, spleen, kidney), chest X-ray and laboratory examination (blood routine, urine routine, blood biochemistry, coagulation function, four items before blood transfusion, fecal occult blood examination) are normal or judged by the investigator to be abnormal of no clinical significance;
5. Participants (including male participants) have no fertility plan and voluntarily take effective contraceptive measures (contraceptive measures other than contraceptive drugs during the trial) from the signing of informed consent until 3 months after the last administration of the Investigational Product, and have no sperm donation and egg donation plans;
6. Able to communicate well with the investigator, and understand and comply with the requirements of the trial.

Exclusion Criteria:

1. People with allergies: allergies to medicines, food, pollen, etc., or those who have a history of allergy to rosuvastatin calcium tablet, Y-3 for injection or any of components of above investigational products;
2. Those who have diseases or medical history that may affect drug absorption, distribution, metabolism, excretion or interpretation of safety data, or diseases or medical history that can reduce compliance, including but not limited to gastrointestinal, renal, hepatic, pulmonary, neurological, hematological, endocrine, tumor, immunologic, psychiatric or cardiovascular and cerebrovascular diseases (especially liver and kidney insufficiency, diabetes, hypoglycemia, bleeding tendency or cachexia, malignant hypertension, thrombocytopenia);
3. Those who with myopathy, myalgia or rhabdomyolysis;
4. Those who have undergone surgery within 6 months prior to the first use of the investigational products, or who have undergone surgeries that may affect the absorption, distribution, metabolism, or excretion of the drug (such as cholecystectomy), or those who plan to undergo surgery during the trial;
5. Participants with a history of needle or blood phobia, intolerance to venipuncture or intravenous administration, or difficulty in blood sampling.
6. Those who cannot follow the uniform diet (e.g., special requirements for diet, intolerance to standard meals, hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption).
7. For patients with creatinine clearance <80 mL/min, creatinine clearance (mL/min) = [(140-age) × body weight (kg)]/[72×Scr(mg/dl)] or creatinine clearance (mL/min) = [(140-age) × body weight(kg)]/[0.818×Scr(μmol/L)], female study participants were × 0.85 according to the calculated results;
8. Those who have participated in or are participating in other clinical trials within 3 months before the first use of the investigational products (drug clinical trial is defined as the use of clinical investigational products), or planning to participate in other clinical trials during the trial period or within 1 month after the end of the trial, or those who do not come to participate in clinical trials in person;
9. Those who have donated blood (including component blood) or had heavy bleeding (>400 ml, except for blood loss during normal menstrual period in women) within 3 months before the first use of the investigational products, or received blood transfusion or used blood products, or planning to donate blood or blood components during the study or within 1 month after the end of the study;
10. Those who have had significant changes in diet or exercise habits within 3 months before the first use of the investigational products;
11. Those who smoke more than 5 cigarettes pre day within 3 months before the first use of the investigational products, or cannot stop using any tobacco products (including any smoking cessation products containing nicotine) within 48 hours before the first use of the investigational products and during the trial;
12. Those who have a history of drug abuse or drug use within 6 months before the first use of the investigational products, or who are positive for drug abuse screening (morphine, methamphetamine, ketamine, tetrahydrocannabinolic acid, dimethylenedioxyamphetamine);
13. Those who have consumed more than 14 units of alcohol per week (1 unit of alcohol ≈ 360 mL of beer or 45 mL of spirits with 40% alcohol content or 150 mL of wine) per week within 3 months before the first use of the investigational products, or who cannot abstain from alcohol or stop using any diet containing alcohol within 48 hours before the first use of the investigational products and during the trial, or have a positive alcohol breath test result (greater than 0.0 mg/100 mL);
14. Those who consume excessive amounts of tea, coffee and/or caffeine-rich beverages (more than 8 cups, 1 cup = 250 mL) every day within 3 months before the first use of the investigational products, or cannot stop using caffeine-rich foods or beverages (such as chocolate, coffee, tea, cola, etc.) within 48 hours before the first use of the investigational products and during the trial;
15. Those who have used any drug with potential interactions with the investigational products within 1 month before the first use of the investigational products;
16. Those who have been vaccinated within 1 month before the first use of the investigational products, or plan to receive any vaccine during the trial or within one week after the end of the trial;
17. Those who have used any prescription medicines, over-the-counter medicines, Chinese herbal medicines, health products and functional vitamins within 14 days before the first use of the investigational products;
18. Those who have one or more positive test results for hepatitis B surface antigen, hepatitis C virus antibody, HIV1/2 antigen/antibody and treponema pallidum antibody;
19. Females of childbearing potential who have had unprotected sex within 14 days prior to the first use of investigational products, or females who are pregnant or lactating, or who have a positive pregnancy test result;
20. Those who cannot stop ingesting grapefruit, dragon fruit, mango, lime, star fruit and other fruits or related products that affect metabolic enzymes within 48 hours before the first use of the investigational products and during the test;
21. Other conditions judged by the investigator to be inappropriate for enrollment.