Safety and Pharmacokinetic Study of ARTS-011 in Chinese Healthy Volunteers

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; Initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug up to the end of study that are absent before treatment or that worsened relative to pretreatment state.

AEs are classified according to the severity in 3 categories:

• mild - AEs does not interfere with participant's usual function
• moderate - AEs interferes to some extent with participant's usual function
• severe - AEs interferes significantly with participant's usual function

Electrocardiogram (ECG)

Physical examinations included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems.

Criteria for abnormalities:

Hematology: hemoglobin, hematocrit, red blood cell count: less than(<) 0.8*lower limit of normal (LLN); platelets: <0.5*LLN or >1.75*ULN, white blood cell count: <0.6*LLN or >1.5*ULN; lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN; eosinophils, basophils, monocytes: >1.2*ULN;

Coagulation: activated partial thromboplastin time, prothrombin, prothrombin international ratio: >1.1*ULN;

Liver function: bilirubin: >1.5*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase: >3.0*ULN; protein, albumin: <0.8*LLN></0>1.2*ULN;

Renal function: blood urea nitrogen, creatinine: >1.3*ULN; uric acid: >1.2*ULN;

Chemistry: sodium, potassium, chloride, calcium, bicarbonate: <0.9*LLN, or >1.1*ULN;

Fasting glucose: <0.6*LLN, or >1.5*ULN;

Urinalysis: pH<4.5, or >8; glucose, protein, blood, ketones, urobilinogen, bilirubin, nitrite.

Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.

Dose normalized (dn) Cmax is calculated by dividing Cmax by the exact dose of ARTS-011 (in mg) administered to a participant.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Clearance obtained after oral dose is influenced by the fraction of the dose absorbed. CL/F =Dose of ARTS-011/AUCinf.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours for MAD once daily.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). AUCinf(dn) was calculated by dividing AUCinf by the exact dose of ARTS-011 (in mg) administered to a participant.

Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours for MAD once daily. AUCtau(dn) is calculated by dividing AUCtau by the exact dose of of ARTS-011 (in mg) administered to a participant.