This study is divided into two parts, including Part I: a randomized, open-label, positive drug-controlled, single ascending dose (SAD) study, a food effect (FE) study, and Part II: a randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study.
Part I: Single Ascending Dose (SAD) and Food Effect (FE) Study Combined SAD and FE Study (N=42): The SAD portion is integrated with the FE study, comprising 5 dose groups: 20 mg, 80 mg, 160 mg, 300 mg, and 600 mg. The trial commences with the low-dose group and in a sequential manner. As subjects in a given dose group of CX2101A complete their safety assessments, the investigator evaluates whether the low-dose group has met the dose-escalation termination criteria. If not, the trial escalates to the next dose level. SAD Study Enrollment: The SAD study aims to enrolls a total of 42 healthy subjects. The 20 mg dose group will enroll 4 subjects, while the 80 mg, 160 mg, and 600 mg dose groups will each enroll 8 subjects. These subjects will be randomly assigned to receive either CX2101A enteric-coated tablets or intravenous remdesivir in a 3:1 ratio. FE Study for the 300 mg Dose Group: The 300 mg dose group will concurrently conduct a study of food effect on the pharmacokinetics (PK) of CX2101A enteric-coated tablets. This study plans to enroll 14 subjects, who will be randomly assigned to receive either CX2101A enteric-coated tablets (12 subjects) or intravenous remdesivir (2 subjects). In the first period, all 14 subjects will receive a single dose under fasting conditions according to the randomization schedule and will have blood samples collected. The 12 subjects receiving CX2101A enteric-coated tablets will undergo a 7-day washout period with a potential adjustment based on PK data from prior dose groups before proceeding to the second period, where they will receive the drug under fed conditions, complete blood sample collection, and undergo safety assessments. Part II: Multiple Ascending Dose (MAD) Study MAD Study Design: The MAD study will include 2 dose groups, 100 mg and 300 mg. It plans to enroll 20 healthy adult subjects, with 10 subjects in each dose group. These subjects will be randomly assigned to receive either CX2101A enteric-coated tablets (8 subjects) or CX2101A placebo (2 subjects). The study will involve continuous dosing for 5 days. If the subjects in the first dose group complete their safety assessments and the investigator determines that the dose-escalation termination criteria have not been met, the study will escalate to the next dose level.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Intravenous remdesivir 100 mg
CX2101A enteric-coated tablet
CX2101A placebo enteric-coated tablet
Zhejiang Xiaoshan Hospital
Hangzhou, Zhejiang, China
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 5 days after treatment
Vital signs
Assessment of blood pressure
Time frame: From day 1 until 5 days after treatment
Vital signs
Assessment of heart rate
Time frame: From day 1 until 5 days after treatment
Vital signs
Assessment of respiratory rate
Time frame: From day 1 until 5 days after treatment
Vital signs
Assessment of body temperature.
Time frame: From day 1 until 5 days after treatment
Electrocardiogram (ECG)
ECG QT Interval
Time frame: From day 1 until 5 days after treatment
Physical examinations
Assessment of head, eyes, ears, nose, and throat, chest, cardiac, abdominal, extremities, neurologic, and lymph node examinations
Time frame: From day 1 until 5 days after treatment
Complete blood count test
Assessment includes Platelet Count, Hemoglobin, WBC Count (absolute), Neutrophils, Lymphocytes, Eosinophils, Monocytes, Basophils
Time frame: From day 1 until 5 days after treatment
Clinical Chemistry
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Assessment includes BUN, Creatinine, Glucose (fasting), Sodium, Total Protein, Magnesium , Potassium, Chloride, Total CO2, Calcium, Albumin, AST (SGOT), ALT (SGPT), Phosphorous, Alkaline phosphatase, Total and direct bilirubin
Time frame: From day 1 until 5 days after treatment
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
Peak Concentration (Cmax): The maximum plasma concentration of the drug.
Time frame: From time zero up to 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
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 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
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 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
Time to Reach Peak Concentration (Tmax): The time at which the peak plasma concentration is reached.
Time frame: From time zero up to 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
Elimination Half-Life (T1/2): The time required for the plasma concentration to decrease by half.
Time frame: From time zero up to 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
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 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
Apparent Clearance (CL/F): The clearance of the drug from the plasma, corrected for bioavailability.
Time frame: From time zero up to 120 hours post-dose
PK profile of CX2101A and its metabolite CX210101,CX210108, CX210144, remdesivir and its metabolite GS-441524
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 120 hours post-dose