This is a randomized, double-blind, placebo-controlled phase I study to evaluate the safety, tolerability, PK profiles and PD effect of single and multiple ascending doses of subcutaneously administered RBD5044 in healthy subjects. The study will be performed in 2 phases: single ascending dose (SAD) phase and multiple ascending doses (MAD) phase in healthy subjects. There are 6 cohorts in SAD phases, the dose levels are 5mg, 20mg, 60mg, 90mg, 120mg and 150mg. There are 3 cohorts in MAD phases, the dose levels are 60mg, 90mg and 120mg.The decision to escalate to subsequent dose levels will be made by the SRC based on the review of all available safety information, including AEs, ECGs, vital signs, and clinical laboratory test results in each cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
Subcutaneously Administered RBD5044 in Healthy Subjects
Subcutaneously Administered Placebo in Healthy Subjects
Q-Pharm Pty Limited
Brisbane, Australia
Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0
The investigator will make an assessment of intensity for each AE and SAE reported during the study according to CTCAE V5.0
Time frame: SAD: Up to 24 weeks; MAD: Up to 28 weeks
To characterize the pharmacokinetic parameter Cmax of RBD5044 in healthy subjects
Plasma Maximum concentration (Cmax)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter Tmax of RBD5044 in healthy subjects
Time to maximum concentration (Tmax)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter AUC0-inf of RBD5044 in healthy subjects
Area under the concentration-time curve from 0 to infinity (inf) (AUC0-inf)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter AUC0-t of RBD5044 in healthy subjects
Area under the concentration-time curve from 0 to the collection time t (AUC0-t)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter t1/2 of RBD5044 in healthy subjects
Plasma Half-Life (t1/2)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter λz of RBD5044 in healthy subjects
Terminal rate constant (λz)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter MRT of RBD5044 in healthy subjects
mean residence time (MRT)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter CL/F of RBD5044 in healthy subjects
Oral clearance (CL/F)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To characterize the pharmacokinetic parameter Vz/F of RBD5044 in healthy subjects
Volume of distribution in the terminal elimination period (Vz/F)
Time frame: SAD: within 60 minutes before dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after dosing; MAD: within 60 minutes before day 1 and day 29 dosing, and at 0.25, 0.5, 1, 2, 4, 6, 8,10,12, 24 and 48 hours after Day 1 and day 29 dosing
To evaluate the pharmacodynamics (PD) effect of RBD5044 on serum levels of APOC3 in healthy subjects
by testing Concentrations of APOC3
Time frame: SAD: Up to 24 weeks; MAD: Up to 28 weeks
To evaluate the PD effect of RBD5044 on serum levels of triglyceride (TG) in healthy subjects.
by testing Concentrations of TG
Time frame: SAD: Up to 24 weeks; MAD: Up to 28 weeks
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