[14C] Study on Mass Balance and Biotransformation of STI-1558 in Healthy Chinese Adult Male Subjects

This trial adopts a single-center, single-dose, single-period, non-randomized, open-label study design. It is planned to enroll 6~8 healthy male subjects, and each subject receives single oral administration of drug solution containing 600mg/approximately 100µCi [14C]STI-1558 under fasting conditions on trial D1. The whole blood, plasma, urine and stool samples are collected at specified time points/intervals during the trial. The pharmacokinetic parameters of the total radioactivity in plasma and whole blood, the material concentration ratios of the total radioactivity in plasma and whole blood, and the material balances are obtained by testing the total radioactivity of [14C]STI-1558 in plasma, whole blood, urine and feces. Meanwhile, using isotope tracer and mass spectrometry techniques, the main pathways and characteristics of metabolism and elimination of STI-1558 in humans are obtained through the quantification of radioactive metabolite profiles and the structure identification of the main metabolites in plasma, urine and feces of the subjects. The entire duration of trial is expected to be 5 months.

Inclusion Criteria:Willing to sign informed consent form;Chinese healthy male subjects between 18-45 years of age (inclusive);Weight: weight ≥ 50.0kg and body mass index (BMI) between 19.0~26.0kg/m2 (inclusive);Male subjects of childbearing potential who have no birth plans throughout the study period and for 12 months after the end of study, and agree to take contraceptive measures with their sexual partners during this period, such as condoms, contraceptive sponges, contraceptive gels, contraceptive films, intrauterine devices, oral or injected contraceptives (only suitable for the period after end of trial), subcutaneous implants (only suitable for the period after end of trial) or other contraceptive measures;Able to communicate well with the investigator and able to complete the trial in accordance with the protocol.Exclusion Criteria:Laboratory tests:Subjects who have clinically significant abnormalities through comprehensive physical examinations, vital signs, routine laboratory tests (blood routine, blood biochemistry, 4-item coagulation function, urine routine, stool routine + occult blood, etc.) and 12-lead ECG;Thyroid-stimulating hormone (TSH) > ULN (upper limit of normal); or free triiodothyronine (FT3) > ULN; or free thyroxine (FT4) > ULN;Blood amylase or lipase > ULN;Subjects who have any positive tests for hepatitis B surface antigen, hepatitis C antibody, treponema pallidum antibody, or combined HIV antigen/antibody test (primary screening);Medication history:Subjects who have received any investigational products (including marketed products) or participated in any clinical trials with drugs/devices within 3 months prior to screening;Subjects who have used any drugs that inhibit or induce liver drug metabolizing enzymes within 30 days prior to screening (such as: inducers - barbiturates, carbamazepine, phenytoin, rifampicin, dexamethasone, rifabutin, rifapentine, etc.; inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, verapamil, imidazole antifungals, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines, etc.);Subjects who have taken any drugs that inhibit gastric acid secretion and gastric antiacids within 14 days prior to screening, such as H2 receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine, roxatidine, etc.); proton pump inhibitors (omeprazole, lansoprazole, rabeprazole, pantoprazole, esomeprazole, etc.); and cholinergic receptor blockers (atropine, pirenzepine, etc.);Subjects who have used prescribed drugs, non-prescribed drugs, or health care medicines including western medicines or Chinese patent medicines within 30 days prior to administration (see exclusion criteria 6 and 7 for restrictions on liver drug metabolizing enzyme drugs, drugs that inhibit gastric acid secretion, and gastric antiacids); or have been vaccinated within 30 days prior to administration or plan to be vaccinated during the trial and within 30 days after end of trial;Medical history and surgery history:Subjects with any history of clinically significant diseases or diseases or conditions that may affect the trial results in opinion of the investigator, including but not limited to history of motor system, nervous system, endocrine system, circulatory system, respiratory system, digestive system, urinary system and reproductive system diseases;Subjects with previous history of organic heart diseases (such as history of heart failure, history of myocardial infarction, history of angina pectoris), history of unexplained arrhythmia (such as history of ventricular tachycardia, history of QT prolongation syndrome) or symptoms or family history (with genetic evidences or close relatives who died suddenly from cardiac causes at a young age) of QT prolongation syndrome;Subjects with coagulation disorders, hemorrhagic diseases (such as hemophilia, purpura) or hemorrhagic symptoms (such as hematemesis, melena, hemorrhage of gastrointestinal tract, serious or recurrent epistaxis, hemoptysis, obvious hematuria or intracranial hemorrhage);Subjects who have suffered esophageal reflux or peptic ulcer diseases, or have received any previous surgical operations that may affect drug absorption (such as cholecystectomy) within 3 months prior to screening;Subjects who have received major surgeries within 6 months prior to screening or have surgical incisions that have not fully healed (see exclusion criteria 12 for surgical operation restrictions that may affect drug absorption); major surgeries include, but are not limited to, any surgeries with significant hemorrhage risks, prolonged general anesthesia periods, incisional biopsies or obvious traumatic injuries (except for appendicitis surgery or anal prolapse surgery that has recovered);Subjects with significant allergic conditions, including subjects who are clearly allergic to two or more other drugs or food ingredients; or subjects with previous history or family history of allergic skin diseases; or subjects who have special dietary requirements and cannot follow a unified diet;Subjects with mental disorders or previous history of mental disorders;Subjects with perianal diseases with concurrent hemorrhoids or regular/current hematochezia;Subjects with habitual constipation or diarrhea, irritable bowel syndrome, or inflammatory bowel diseases;Living habits:Subjects who are alcoholics or regular drinkers within 6 months prior to screening, that is, consuming more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of spirits with 40% alcohol or 150 mL of wine); or have positive results of alcohol breath tests during the screening period and baseline period; and cannot abstain during the trial;Subjects who smoke more than 5 cigarettes per day or habitually use nicotine-containing products in 3 months prior to screening, and cannot abstain during the trial;Subjects who abuse drugs or have used soft drugs (such as: marijuana) in 3 months prior to screening or hard drugs (e.g.: cocaine, amphetamines, phencyclidine, etc.) within 1 year prior to screening; or have positive results of urine drug abuse tests during the screening period and baseline period;Subjects who habitually drink grapefruit juice or excessive tea, coffee and/or caffeinated beverages and cannot abstain during the trial or have previous withdrawal syndrome;Other:Subjects who cannot tolerate venipuncture, or have history of fear of needles and hemophobia;Subjects who are engaged in work with long-term exposure to radioactive conditions; or have significant radioactive exposure within 1 year prior to the trial (≥2 chest/abdominal CT, or ≥3 other types of X-ray examinations) or have participated in trials with radiolabeled drugs;Subjects who have had blood loss or donated more than 400 mL of blood within 3 months prior to screening, or received blood transfusion within 1 month;Subjects who have any other factors that are not suitable for participating in this trial in opinion of the investigator.Subjects who have any other factors that are not suitable for participating in this trial in opinion of the investigator.