Zhejiang ACEA Pharmaceutical Co., Ltd.

This is a first-in-human, dose-escalation and dose-expansion Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of STI-8591 in subjects with advanced AML who have signed an informed consent form (ICF) and have been screened for enrollment in this study.
* Dose escalation phase: rapid titration and conventional 3+3 test design were used to evaluate the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and PK characteristics of STI-8591.
* Dose Expansion Phase: Evaluate the safety, preliminary efficacy and determine the recommended phase II dose (RP2D) of STI-8591 for the treatment of subjects with advanced AML under the conditions of reaching the expanded dose.

This study is a randomized, open, single-dose, two-sequence, two-cycle, double-cross design bioequivalence study.
32 eligible subjects will be randomly assigned to TR group and RT group in a 1:1 ratio. Subjects in the TR group will take the test preparation (T) 200 mg/ pill × 1 pill on day 1 (D1) and the reference preparation (R) 200 mg/ pill × 1 pill on day 8 (D8). The sequence of medication in RT group is reversed from TR group. Wash for at least 7 days between doses.
Screening was performed within 28 days prior to initial dosing, and all eligible subjects were admitted to the clinical research Center 1 day prior to Cycle 1 dosing (D-1) and discharged on day 10 of the study (D10) after completing Cycle 2 PK blood collection, corresponding safety examination, and evaluation. On the 14th day of the study (± 1 day), the clinical research center was returned for follow-up to further evaluate the safety and tolerability of the 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.