A Phase I Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single- and Multiple-Ascending Doses of RS1805 Tablets in Healthy Adult Subjects

Exclusion Criteria24

• Suspected allergy to the study drug or any component of the study drug, or allergic constitution
• History of malignant tumor; with the exception of subjects with non-melanoma skin cancer that was cured > 2 years ago and cervical intraepithelial neoplasia that was cured > 5 years ago.
• Subjects have any surgical operation within 3 months prior to screening, or subjects have not recovered from prior surgery as judged by investigators, or plan to receive the operation during the study and within 1 month after completing all study visits
• History of clinical major heart disease, liver disease, nerve disease, respiratory disease, blood disease, digestive disease, immune disease, kidney disease or mental disease, which is considered by the investigator to confuse the study results or affect absorption, distribution, metabolism and excretion of drug or place the subjects at improper risks
• Any disease that affects drug absorption, distribution, metabolism and excretion as judged by the investigator (e.g., gastrointestinal dysfunction, peptic ulcer, gastrointestinal surgery, etc.);
• Active tuberculosis indicated by clinical symptoms, signs, laboratory tests or chest X-ray; latent tuberculosis indicated by T-spot or Quanti-FERON TB test
• Investigator-judged clinically significant infections within 1 month prior to screening, including acute and chronic infections such as abscess, furuncle, carbuncle and other local infections, respiratory tract infections, urinary and reproductive infections, systemic infections, etc. Minor skin or respiratory infections that have completely resolved even within 1 month are acceptable at the discretion of the investigator
• Participation in any clinical trial of drug or medical device within 3 months prior to screening (or 5 half-lives of drug, whichever is longer);
• Any acute disease with clinical significance as judged by the investigator within 1 month prior to screening
• Subjects who cannot discontinue CYP3A inducers or CYP3A inhibitors 14 days prior to baseline visit and during the study
• Subjects who have received any live vaccine within 1 month prior to screening or need to receive live vaccine during the study (including 30 days after the last dose of study drug);
• Use of prescription drug within 14 days prior to baseline and during the study, with the exception of hormonal contraception, topical medications at the discretion of the investigator, brief use of medications for non-exclusionary conditions that are not expected to interfere with safety or data quality at the discretion of the Principal Investigator and Sponsor
• Use of over-the-counter drugs, including natural health products (e.g., food supplements and herbal supplements) within 14 days prior to baseline, with the exception of occasional use of paracetamol (up to 2 g daily), ibuprofen, or regular doses of vitamins
• QTc greater than 450 ms or other significant ECG abnormalities with clinically significance as judged by the investigator.
• White blood cell count, neutrophil count, lymphocyte count or hemoglobin in hematology exceed the normal reference range and is judged as clinically significant by the investigator.
• Alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN) and/or aspartate aminotransferase (AST) > 1.5 times ULN and/or bilirubin > 1.5 times ULN;
• Estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m² calculated by the Modification of Diet in Renal Disease (MDRD)
• Patients who are positive for hepatitis B surface antigen, hepatitis B e antigen, antihepatitis C virus antibody, syphilis antibody, or HIV antibody.
• Other laboratory test results exceed the laboratory normal reference range, based on which the investigator determines that the subject is not suitable to participate in this study. General conditions:
• Subjects who plan to have a child or donate sperm during the study or within 90 days after the last dose of study drug.
• Smokers: An average daily smoking of more than 5 cigarettes (or other nicotine containing products) at the time of screening.
• Drinkers: Positive breath alcohol test (positive with equals to 0 mg/dl) at screening; or long-term fixed alcohol consumption within 3 months prior to screening, the subject drinks more than 14 units of alcohol per week, [1 unit equals to150 mL of wine, rice wine or low-grade liquor, 360 mL of beer, or 45 mL of high-grade (greater than 40 degrees) liquor];
• Drug abusers: Positive in urine drug screening test.
• Women who are pregnant or breastfeeding