This is a Phase 1, Double Blind, Randomized, Placebo Controlled, Single Dose, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ZD03 Capsule in Healthy Volunteers in The United States
ZD03 is a novel small molecular drug. It is a synthetic chemical drug candidate for treatment of multiple sclerosis (MS) and is proposed to be administered orally as capsules. This is a double-blind, randomized, placebo-controlled, single ascending dose study. Approximately 56 HVs will enter into the phase 1 study. The study is designed to evaluate the safety,tolerability and PK of ZD03 capsule at different dose cohorts when administered orally. Subjects who meet the enrollment criteria will be enrolled in one of the seven dose levels designated for the study, including the doses of 20, 40, 80, 120, 180, 240 and 300 mg (doses escalated by 100%, 100%, 50%, 50%, 33% and 25%, respectively). Each cohort will consist of 8 subjects randomized at 3:1 to receive a single oral dose of ZD03 (n=6) or placebo (n=2) in a double-blind manner in a fasted state
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
Worldwide Clinical Trials,Early Phase Services, LLC
San Antonio, Texas, United States
safety and tolerability
Safety and tolerability will be assessed by monitoring adverse events (AEs), several adverse events (SAEs)
Time frame: Up to 14 days
Number of participants with clinically significant Vital sign abnormalities will be assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Vital signs including sitting blood pressure, pulse rate, respiration rate and oral temperature.
Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities will be assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Resting 12-lead ECGs will use a standard 12-lead ECG machine that automatically calculates HR and measures RR, PR, QRS, QT and QTc intervals.
Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
Number of participants with clinically significant physical examination abnormalities will be assessed by discretion of the investigator
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Physical examination including the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities.
Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
Number of participants with clinically significant haematology assessment abnormalities will be assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Haematology including Basophils (abs), Eosinophils (abs), Hemoglobin, Monocytes (abs), Neutrophils (abs), Platelets, RBC and WBC, etc.
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Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
Number of participants with clinically significant serum chemistry assessment abnormalities will be assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Serum chemistry including Magnesium, Albumin, Phosphorus, Potassium, Sodium, Total Bilirubin, Total Protein, and Triglyceride, etc.
Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
Number of participants with clinically significant urinalysis assessment abnormalities will be assessed by Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1
Assessed as number of participants with clinically significant changes from Baseline, compared across arms. Urinalysis including Bilirubin, Clarity, Color, Glucose, Ketone, Leukocyte, esterase, Protein, Specific, gravity, and Urobilinogen, etc.
Time frame: Screening, Day -1 to Day 1, Day 2 and Day 7
PK parameters-AUC0-t
area under the concentration-time curve from time 0 to the time of last quantifiable concentration (tlast), calculated using the linear trapezoidal rule for increasing concentrations and the logarithmic rule for decreasing concentrations
Time frame: Up to 24 hours
PK parameters-AUC0-∞
area under the concentration-time curve from time 0 extrapolated to infinity
Time frame: Up to 24 hours
PK parameters-Cmax
maximum observed plasma concentration
Time frame: Up to 24 hours
PK parameters-tmax
time of maximum observed plasma concentration
Time frame: Up to 24 hours
PK parameters-t1/2
apparent plasma terminal elimination half-life
Time frame: Up to 24 hours
PK parameters-CL/F
apparent total plasma clearance
Time frame: Up to 24 hours
PK parameters-Vz/F
apparent volume of distribution during the terminal elimination phase
Time frame: Up to 24 hours