In Vivo Absorption, Metabolism, Excretion (AME) Clinical Study of [14C]Afuresertib in Healthy Chinese Male Adults - Human Mass Balance and Biotransformation Study of [14C]Afuresertib

LAE002CN1001

This study adopts a single-center, single-dose, non-randomized, open-label design with a proposed enrollment of 6-10 healthy male subjects. After a single oral dose of approximately 125 mg/150 µCi \[14C\]Afuresertib tablets, blood, urine and fecal specimens are collected from each subject at defined time points/periods during the trial, and PK parameters, recovery, and excretion routes of \[14C\]Afuresertib in plasma are calculated by measuring the total radioactivity. The main metabolic and elimination pathways and characteristics of Afuresertib in human, as well as circulating metabolites with close to or higher than 10% of plasma total radioactivity exposure, are also identified by plasma, urine, and fecal radioactive metabolite profiles and major metabolite structure.

2022-08-06

2022-10-21

2022-10-21

Completed

Early phase I

6

Inclusion Criteria: 1. Healthy male adults; 2. Aged 18-45 years (inclusive); 3. BMI: 19-26 kg/m2 (inclusive); body weight ≥ 50 kg; 4. Willing to sign the Informed Consent Form (ICF); 5. Capable of communicating well with investigators and completing the entire study as required. Exclusion Criteria: 1. Abnormal and clinically significant results of physical examination, vital signs, laboratory tests (routine hematology, blood biochemistry, coagulation function, routine urinalysis, fecal occult blood, thyroid function), 12-lead ECG, chest X-ray, and abdominal B-mode ultrasound (liver, gallbladder, pancreas, spleen, kidney); 2. Resting QT interval corrected with Fridericia's formula (QTcF) ≥ 450 ms shown on the 12-lead ECG; 3. Positive for hepatitis B surface antigen or E antigen, IgG antibody against hepatitis C virus (Anti-HCV IgG), antihuman immunodeficiency virus antigen/antibody (HIV-Ag/Ab) Combo Assay, and treponema pallidum antibody; 4. Clinically significant CRP abnormality in SaRS-CoV-2 infection screening or positive for SARS-CoV-2 nucleic acid test; 5. Use of any drug that inhibits or induces liver drug-metabolizing enzymes within 30 d before screening (see Appendix 1 for details); 6. Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines or food supplements, such as vitamins and calcium supplements, within 14 d before screening; 7. History of diabetes mellitus and/or pancreatitis; 8. History of any serious disease or condition that may affect the study results in the opinion of the investigators, including but not limited to disorders of the circulatory system, respiratory system, endocrine system, nervous system, digestive system, urinary system, or blood, immune, mentality, or metabolism diseases; 9. History of structural heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torsades de pointes, ventricular tachycardia, atrioventricular block, long QT syndrome (LQTS), symptoms or family history of LQTS (indicated by genetic evidence or sudden death of close relatives due to cardiac causes at a young age); 10. Reception of major surgery (included but not limited to any surgery with significant risk of bleeding, prolonged general anesthesia, or significant traumatic injury, or incisional biopsy) within 6 months before the screening period, unhealed surgical wounds; 11. Allergic constitution, history of allergy to two or more substances; possibly allergic to the investigational product or its excipients as judged by the investigator; 12. Hemorrhoids or perianal disease with regular/ongoing hematochezia, irritable bowel syndrome, inflammatory bowel disease. 13. Habitual constipation or diarrhea; 14. Alcoholism or regular alcohol consumption within 6 months before screening period, that is, drinking volume \> 14 U of alcohol per week (1 U = 360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine); breath alcohol test result \> 0 mg/100 mL during the screening period; 15. Consumption of more than 5 cigarettes per day or habitual use of nicotine-containing products within 3 months before the screening period, and unable to abstain during the study; 16. Abuse of drugs or use of soft drugs (e.g., marijuana) 3 months before the screening period or use of hard drugs (e.g., cocaine, amphetamine, phencyclidine, etc.) 1 year before the screening period; or positive for urine drug test during the screening period; 17. Habitual consumption of grapefruit juice or excessive tea, coffee and/or caffeinated beverages, and unable to abstain during the study; 18. Long-term exposure to radioactivity, significant radioactive exposure (≥ 2 chest/abdomen CTs, or ≥ 3 other types of X-ray examinations) or participation in radiolabeled drug trials within 1 year prior to the study; 19. History of needle or blood sickness, difficulty in collecting blood, or intolerance of venipuncture blood collection; 20. Participation in any other clinical trial (including drug and device) within 3 months before the screening period; 21. Vaccination within 1 month before the screening period or scheduled vaccination during the study; 22. Scheduled for fathering or sperm donation during the study and within 1 year after the study; unwilling to take strict contraceptive measures during the study and within 1 year after the study (see Appendix 3 for details); 23. Blood loss or blood donation ≥ 400 mL within 3 months before the screening period, or blood transfusion within 1 month; 24. Any factors that render the subjects unsuitable for participating in this study (determined by the investigators).

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 6, 'type': 'ACTUAL'}}

2023-05-15