The study comprises three parts: single ascending dose (SAD) studies of CX2101A tablets at 40 mg, 100 mg, and 160 mg; a relative bioavailability (BA) study comparing single-dose administration of 100 mg CX2101A tablets and enteric-coated tablets; and a multiple ascending dose (MAD) study of CX2101A tablets. The BA study (100 mg) is integrated into the SAD study(Nested within the SAD protocol to optimize resource utilization).
1. Randomized, Double-Blind, Placebo-Controlled Design All studies are conducted under standardized fasting conditions to eliminate food interference Blinding is maintained throughout the entire study period for both subjects and investigators 2. Single Ascending Dose (SAD) Study Dose Groups: 40 mg, 100 mg, 160 mg (3 cohorts) Subject Allocation: 10 subjects/cohort (8 CX2101A + 2 placebo) Integration with BA Study: The 100 mg cohort will serve as the reference for bioavailability evaluation Subjects completing SAD phase will proceed to receive enteric-coated formulations 3. Multiple Ascending Dose (MAD) Study Dose Groups: Same 40 mg, 100 mg, 160 mg cohorts Subject Allocation: 10 subjects/cohort (8 CX2101A + 2 placebo) Administration Schedule: Daily dosing for 5 consecutive days Relative Bioavailability (BA) Study 4. Cohort Integration: Conducted within the 100 mg SAD group (N=10) Treatment Sequence: Initial single-dose administration of CX2101A tablets ≥7-day washout period (PK data-driven adjustment) Second single-dose administration of enteric-coated tablets Subject Allocation: CX2101A tablets group: 8 subjects (CX2101A + 8 placebo) Enteric-coated group: 8 subjects (CX2101A + 8 placebo)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
Zhejiang Xiaoshan Hospital
Hangzhou, China
PK profile of CX2101A and its metabolite CX210101 and CX210108
Peak Concentration (Cmax): The maximum plasma concentration of the drug.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Area Under the Curve from Time Zero to the Last Measurable Concentration (AUC0-t): The area under the plasma concentration-time curve from time zero to the last measurable concentration.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Area Under the Curve from Time Zero Extrapolated to Infinity (AUC0-∞): The area under the plasma concentration-time curve from time zero extrapolated to infinity.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Time to Reach Peak Concentration (Tmax): The time at which the peak plasma concentration is reached.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Elimination Half-Life (T1/2): The time required for the plasma concentration to decrease by half.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Apparent Volume of Distribution (Vz/F): The volume into which the drug appears to be distributed, corrected for bioavailability.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
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CX2101A placebo enteric-coated tablet
PK profile of CX2101A and its metabolite CX210101 and CX210108
Apparent Clearance (CL/F): The clearance of the drug from the plasma, corrected for bioavailability.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
PK profile of CX2101A and its metabolite CX210101 and CX210108
Percentage of AUC Extrapolated (AUC\_%Extrap): The percentage of the total AUC that is extrapolated beyond the last measurable concentration.
Time frame: From time zero up to 96 hours post-dose following last dose of CX2101A
Rate and severity of treatment-emergent adverse events (TEAEs)
Based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Time frame: From day 1 until 4 days after treatment
Vital signs
Number of participants with abnormal results of vital signs.
Time frame: From day 1 until 4 days after treatment
Electrocardiogram (ECG)
Number of participants with abnormal results of electrocardiogram.
Time frame: From day 1 until 4 days after treatment
Physical examinations
Number of participants with abnormal results of physical examinations
Time frame: From day 1 until 4 days after treatment
Complete blood count test
Number of participants with abnormal results of complete blood count test.
Time frame: From day 1 until 4 days after treatment
Clinical Chemistry
Number of participants with abnormal results of clinical chemistry.
Time frame: From day 1 until 4 days after treatment