[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.

The experiment was carried out in two steps : Step 1 : Two qualified male subjects were enrolled in the study. After screening, the qualified subjects were admitted to the clinical research center after the D-2 was again verified by the inclusion and exclusion criteria. After admission, they were trained in medication, urine and feces collection procedures to ensure that they could perform relevant operations according to the program and SOP requirements. D-1 began to collect random urine samples ( -24 h\~0 h ) and D-2 began to collect random fecal samples ( -48 h\~0 h ). Subjects tested D1 morning fasting oral test drugs. All urine and feces samples excreted within the specified time interval of 0\~336 h and blood samples at the specified time point of 0\~168 h were collected. The test adopts the method of phased detection. According to the test results, it is judged whether the collection of blood, urine and feces samples can be terminated in advance or the collection needs to be continued. If the study finds that the collection time of biological samples exceeds the planned time ( i.e., blood 168 h, urine and feces 336 h ), the collection will be continued at an interval of 24 h ( or according to the researcher 's judgment, the integer multiple of 24 h ) until the judgment criteria for the termination of sample collection specified in the scheme are met. Safety monitoring continued until sample collection was completed. Step 2 : 4-6 qualified male subjects were selected and blood, urine and feces samples were collected at the specified time points / intervals. The operation is the same as the first step. According to the test results of the first step test, determine whether the test process needs to be adjusted. Criteria for terminating collection: Excreta : The total radioactivity of biological samples ( urine + feces ) collected from each subject exceeded 90 % of the dose, and the total radioactivity of biological samples ( urine + feces ) collected for two consecutive days was less than 1 % of the dose ; radioactive blood samples : plasma radioactive concentration \< 3 times plasma background value. Finally, whether the subjects should terminate the collection of the corresponding samples was determined by the researchers based on the results of the radioactive test, the safety results and the actual situation, and the opinions of the sponsors. All subjects were required to complete the test procedure according to the program requirements during their stay in the clinical research center. The subjects who met the radioactive recovery conditions were collected in the laboratory examination samples, and no clinically significant abnormalities were found in the clinical observation, and the group could be confirmed by the researchers. If the abnormality is found to have clinical significance, the subjects will need to remain in the research center for observation or after the comprehensive evaluation of the researchers, agree to leave the research center and return to the hospital for regular review ( according to the requirements of the researchers ), follow-up until the normal or abnormal level is returned to normal or not clinically significant or acceptable to the researchers.