The Pharmacokinetics (PK), Pharmacodynamics(PD), Safety, Tolerability of SR1375 in Healthy Volunteers

The study is a Phase I study to evaluate the PK, PD, safety, and tolerability of SR1375 in healthy volunteers. The study will include 3 single-ascending-dose (SAD) cohorts and 1 multiple-dose cohorts (Part A and part B respectively), a total of 4 cohorts, and each cohort includes 3 stages: screening and baseline, treatment and safety monitoring, and safety follow-up.

Inclusion criteria

• Healthy males and females who are 18 to 45 years of age.
• Based on medical history, physical examination, laboratory examination, chest CT scan, abdominal B-ultrasound, vital signs and ECG, the investigator considered that the results were normal or abnormal but no clinical significance.
• Bodyweight of male > 50 kg, Bodyweight of female > 45 kg and body mass index (BMI) between 18 and 28 kg/m2.
• Male subjects must agree to use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug, and must be willing not to donate sperm.
• Healthy female volunteers must be:

i. Of non-childbearing potential(with a documented tubal ligation, bilateral salpingectomy, hysterectomy, or menopause for more than 1 year) ii. Of childbearing potential, must have a negative pregnancy test at the screening visit (blood test), must agree to use a highly effective contraceptive method from signing the consent form until at least 30 days after the last dose of study drug.

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion criteria

• History of hypercoagulable state or history of thrombosis.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities.
• History of sensitivity to any of the investigational medicinal products (IMPs), or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation.
• History of asthma (excluding resolved childhood asthma), severe allergic responses.
• History of significant drug abuse within one year of screening.
• Except for topical (no significant systemic exposure) permitted, use of the following combination agents will be excluded:

• Use of prescription drugs within 14 days prior to initial administration, or within 7 days or five half-lives of the medication (whichever is longer) prior to the first study drug administration, except occasional use of paracetamol (up to a maximum of 2000 mg per day of paracetamol and per local or national abelling).
• Use the health supplement 7 days or 5 half-life before the first administration of the investigational drug.
• Use of depot injection or subcutaneous implantation drugs within 3 months prior to the first study drug administration.
• Received vaccine within 1 month prior to the first administration of the investigational drug.
• A positive Hepatitis B surface antigen, positive Hepatitis C antibody and positive test for human immunodeficiency virus (HIV) antibody or treponema pallidum antibody.
• A positive drug/alcohol result.
• History of regular alcohol consumption within 6 months of screening defined as:

an average weekly intake of >14 units (1 unit of alcohol ≈360 mL beer or 45 mL 40% alcohol spirits or 150 mL wine), or abstain from alcohol during the study.

• Within 6 months of screening, smoking more than 5 cigarettes(including e- cigarettes).
• Donation or lost in excess of 400 mL of blood within 2 months of Day 1 or donation of plasma within 14 days of Day 1.
• The subject has participated in a clinical trial within 3 months of receiving IMP.
• Unable to refrain from consumption of Seville oranges, grapefruit or grapefruit juice within 24h prior to the first dose of IMP until the Safety Follow-up visit.
• Breast-feeding and/or lactating subject.
• Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.