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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RBD5044 SAD experimental group | Experimental | Subjects in SAD experimental groups will receive a single subcutaneous injection of RBD5044 on Day 1. |
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| RBD5044 MAD experimental group | Experimental | Subjects in MAD experimental groups will receive one subcutaneous injection of RBD5044 on Day 1 and another subcutaneous injection of RBD5044 on Day 29. |
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| Placebo SAD group | Placebo Comparator | Subjects in SAD placebo groups will receive a single subcutaneous injection of placebo on Day 1. |
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| Placebo MAD group | Placebo Comparator | Subjects in MAD placebo groups will receive one subcutaneous injection of placebo on Day 1 and another subcutaneous injection of placebo on Day 29. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RBD5044 | Drug | Subcutaneously Administered RBD5044 in Healthy Subjects |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 | SAD: Up to 24 weeks; MAD: Up to 28 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| To characterize the pharmacokinetic parameter Cmax of RBD5044 in healthy subjects | Plasma Maximum concentration (Cmax) | 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 |
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Inclusion Criteria:
A subject will be eligible for inclusion in this study only if all of the following criteria are met:
Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent.
Male and female subjects, aged 18 to 65 years (inclusive).
Body mass index between 18 and 32 kg/m2, inclusive.
Fasting TG ≥ 0.9 mmol/L (80 mg/dL) and ≤ 3.4 mmol/L (300 mg/dL) at screening.
Fasting LDL-C < 4.9 mmol/L (<190 mg/dL) at screening.
Healthy as determined by pre-study medical history, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG).
Satisfy one of the following:
Non-smokers and non-nicotine users for at least 90 days before screening
Exclusion Criteria:
A subject meeting any of the following exclusion criteria will not be allowed to participate in this study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Q-Pharm Pty Limited | Brisbane | Australia |
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double-blinded
| Placebo | Drug | Subcutaneously Administered Placebo in Healthy Subjects |
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| To characterize the pharmacokinetic parameter Tmax of RBD5044 in healthy subjects | Time to maximum concentration (Tmax) | 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) | 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) | 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) | 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) | 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) | 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) | 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) | 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 | 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 | SAD: Up to 24 weeks; MAD: Up to 28 weeks |