Phase 1 study

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria：

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.

• Adult males and females between ≥ 18 and ≤ 55 years (inclusive) at Screening.

• Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 with a body weight ≥ 50 kg (males) or ≥45 kg (females) at Screening.

• Participants with normal results or non-clinically significant (NCS) abnormal results in the opinion of the PI or delegate for a comprehensive examination, including physical examination, vital signs examination, laboratory tests (hematology, biochemistry, coagulation and urinalysis).

• a)Female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

  • Women of non-childbearing potential (WONCBP), defined as surgically sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (no menses for 12 months and confirmed by follicle stimulating hormone [FSH] level >40 mIU/mL);
  • Woman of childbearing potential (WOCBP) and agree to practice true abstinence or agrees to use an highly effective method of contraception (refer to Section 4.6.3) consistently from the signing of informed consent form (ICF) to 90 days after the last dose of IPs and refrain from donating eggs during this period. And WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Day -1.
  • Participant is in an exclusively same-sex relationship. b)Male participants must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior to screening and documented to no longer produce sperm - verbal confirmation through medical history review acceptable); or agree to use a condom plus effective contraception methods (refer to Section 4.6.3) for their female partner, if of childbearing potential, from the signing of ICF to 90 days after the last dose of IPs and refrain from donating sperm during this period. These contraception requirements do not apply if the male participant is in an exclusively same sex relationship.

• Able and willing to attend the necessary visits to the study site. Exclusion Criteria：

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, musculoskeletal, rheumatological, psychiatric , systemic, ocular, or infectious disease, or signs of acute illness.

• Any history or presence of depression.

• Any history or presence of gastrointestinal, hepatic, renal disease that affect drug absorption or metabolism.

• Any surgery within 1 months prior to the first dose.

• Any history or presence of chronic infectious diseases such as tuberculosis (judged by the Investigator according to QuantiFERON gold).

• Participants with a clinically significant infection history within 4 weeks prior to first dose, or any serious infection requiring intravenous antimicrobial therapy within 6 months prior to Screening.

• Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) at Screening or Day -1.

• Participants with clinically significant abnormal 12-lead electrocardiogram (ECG) results as judged by the PI or delegate or with a corrected QTc (formula: QTcF = QT/RR1/3) interval greater than 450 msec in males and 470 msec in females.

• Participants with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), treponema pallidum antibody (Syphilis TP Ab) or human immunodeficiency virus antibody (HIV Ab) at Screening.

• Participants with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 (using the CKD-EPI equation).

• Presence or history of drug/food hypersensitivity, or anaphylactic reaction, diagnosed and treated by a physician, or have special dietary requirements.

• Known hypersensitivity to any component of the IP formulation.

• Participants who regularly drink more than 14 standard units of alcohol per week for females and more than 21 standard units of alcohol per week for males; 1 standard unit contains 10 g of alcohol, such as 285 mL of beer, 30 mL of 40% spirits or 100 mL of wine within 6 months prior to Screening.

• Participants with a history of drug abuse or a positive drug abuse screening test.

• Regular smoking (defined as more than 5 cigarettes or equivalent per week) within one year prior to the first dose, or unable to stop smoking from 48 hours prior to the first drug administration to the last time point for collecting PK blood samples.

• Positive alcohol test at screening and check-in on D-1.

• Any consumption of xanthine bases and/or grapefruit or products containing xanthine bases and/or grapefruit within 2 weeks prior to the first dose; or unable to stop consumption of above ingredients from first drug administration to the last time point for collecting PK blood samples.

• Any consumption of chocolate or caffeine or products containing caffeine within 48 h prior to the first dose; or unable to stop consumption of above ingredients from first drug administration to the last time point for collecting PK blood samples.

• Any consumption of alcohol or products containing alcohol within 48 h prior to Day-1; or unable to stop consumption of alcohol first drug administration to the last time point for collecting PK blood samples.

• Any drug that inhibits or induces liver drug metabolism (inducers include barbiturates, carbamazepine, rifampicin, phenytoin, glucocorticoids, omeprazole, etc.; inhibitors include selective serotonin reuptake inhibitor (SSRI) antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines, etc.) within 30 days prior to the first dose or during the study.

• Any prescription medication, within 14 days prior to administration of the first dose or within 5 times the elimination t1/2 of the medication, with the exception of hormonal contraception, menopausal hormone replacement therapy or occasional analgesics such as Paracetamol, Ibuprofen and standard daily vitamins etc. in short term at the Investigator's direction.

• Made a blood donation > 400 ml within 4 weeks prior to the first dose or during the study or planning to donate blood during the study and follow up period.

• Any participant who enrolled in or participated in any other clinical study involving an IP, or in any other type of medical research within 1 month or within 5 times the elimination t1/2 prior to administration of the first dose.

• Any vaccination in the 14 days prior to administration of the first dose.

• Any participant in whom venous blood collection is difficult.

• Any participant who, in the judgment of the Investigator, is likely to be non-compliant during the study, or to be unable to cooperate due to language problems or poor mental development.

• Any participant who is the Investigator or any subinvestigator, research assistant, pharmacist, study coordinator, or other staff thereof directly involved in conducting the study or any person dependent on (employees or immediate family members) the study site, the Investigator or the Sponsor.