Fáze 1 studie bezpečnosti a farmakokinetiky přípravku YN001 s rosuvastatinem u zdravých čínských subjektů

Inclusion Criteria:

1. Fully understand the purpose, characteristics, research methods and potential adverse reactions of this study, voluntarily participate in the study as a subject, and sign the Informed Consent Form (ICF) before any assessments are performed.
2. Healthy Chinese male and female subjects aged 18 to 55 years (inclusive, based on the age at the time of signing the ICF).
3. Body weight ≥ 50 kg for males and ≥ 45 kg for females; body mass index (BMI) ranging from 18 to 28 kg/m² (including the critical values).
4. Judged by the investigator based on medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), laboratory tests (blood routine, blood biochemistry, urine routine, coagulation function) and viral serological test results (normal or abnormal without clinical significance) to be in good general health.
5. Female subjects must be non-pregnant and non-lactating; female subjects of childbearing potential (including female partners of male subjects) must agree to use effective contraceptive methods such as abstinence, condoms, intrauterine devices in use, double barrier methods (e.g., condoms plus diaphragms) from the screening period until 6 months after receiving the last dose of the study drug.
6. Willing and able to comply with the requirements of the study protocol.

Exclusion Criteria:

1. Participation in other clinical trials within 3 months prior to the first dose or within 5 half-lives (whichever is longer). Subjects who withdrew from the study before receiving the study drug (i.e., not administered the drug) are eligible for enrollment.

2. Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or health supplements within 2 weeks prior to the first dose, or receipt of any type of vaccination.

3. Consumption of diets that may affect the in vivo metabolism of drugs (including grapefruit or grapefruit products, pitaya, mango, etc.) within 7 days prior to screening, engagement in strenuous exercise, or consumption of other diets that the investigator deems may affect the absorption, distribution, metabolism, or excretion of drugs.

4. History of severe food allergies (e.g., anaphylactic shock). Mild food allergies such as lactose intolerance and glucose intolerance are not excluded.

5. Allergy to multiple drugs, history of allergy to rosuvastatin, or history of allergic reactions to any component of the study drugs.

6. Known presence of clinically significant abnormal diseases or factors, including but not limited to clinically significant abnormalities in abdominal color Doppler ultrasound (liver, gallbladder, spleen, pancreas, bilateral kidneys, ureters, urinary bladder), chest posteroanterior radiography, etc.; or clinically significant diseases (including but not limited to diseases of the digestive system, circulatory system, respiratory system, endocrine system, urinary system, immune system, nervous system, and mental and psychological diseases) shown by other clinical findings within 6 months prior to screening.

7. History of myopathy/myalgia, or predisposition to myopathy/rhabdomyolysis (e.g., family history of hereditary myopathy, previous combined use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors and fibrates, etc.).

8. Presence of hypothyroidism or hyperthyroidism.

9. History of acute or chronic bronchospastic diseases (including asthma, chronic obstructive pulmonary disease, whether treated or not) or heart failure, myocardial infarction, with a history of onset or recurrence within the past 3 years.

10. Known history of inflammatory bowel disease, ulcers, gastrointestinal bleeding, or rectal bleeding within 6 months prior to the first dose.

11. History of pancreatic injury or pancreatitis within 6 months prior to dosing.

12. Presence of symptoms of urinary tract obstruction or dysuria.

13. History of autonomic nervous system disorders (e.g., recurrent syncope, palpitations, etc.), with a history of onset or recurrence within the past 3 years.

14. Suffering from a major unhealed disease within 2 weeks prior to the first dose; or expected to undergo major surgery during the study period.

15. History of renal impairment, manifested by clinically significant abnormalities in creatinine, blood urea nitrogen (BUN) and/or urea levels, or clinically significant abnormalities in urine components (e.g., proteinuria).

16. Presence of liver disease or liver injury, or abnormal liver function test results. Subjects who meet any of the following criteria must be excluded from the study:

    1. Any one of alanine aminotransferase (ALT), aspartate aminotransferase (AST), or serum bilirubin exceeds 1.5 times the upper limit of normal (ULN).
    2. Any two or more of ALT, AST, or serum bilirubin exceed the upper limit of normal (ULN).

17. History of clinically significant electrocardiogram (ECG) abnormalities; or presence of any of the following abnormalities during screening or baseline period:

    1. QTcF (males) > 470 milliseconds (msec).
    2. QTcF (females) > 480 milliseconds (msec). (Corrected by the Frederica formula, calculated as QTcF = QT/(RR⁰·³³))

18. Screening test shows hemoglobin level < 120 grams per liter (g/L) in males and < 110 grams per liter (g/L) in females.

19. Blood donation or blood loss exceeding 400 milliliters (mL) within 3 months prior to screening.

20. Smoking more than 10 cigarettes per day or habitual use of nicotine-containing products within 3 months prior to screening.

21. History of drug abuse within 12 months prior to screening; or use of any illegal drugs within 3 months prior to screening; or positive results in drug abuse tests (e.g., amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, morphine, etc.) during screening.

22. Weekly alcohol consumption exceeding 14 standard drinking units (1 standard drinking unit = 285 mL of beer, or 25 mL of spirits, or 150 mL of wine) within 3 months prior to screening; or consumption of alcohol-containing products within 48 hours prior to the first dose; or positive results in breath alcohol test during the baseline period.

23. Positive results in tests for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody.

24. The investigator deems the subject unsuitable for participation in the study due to any other diseases or conditions.