Health Volunteer
Conditions
Brief summary
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.
Interventions
DRUGRBD5044
Subcutaneously Administered RBD5044 in Healthy Subjects
DRUGPlacebo
Subcutaneously Administered Placebo in Healthy Subjects
Sponsors
Suzhou Ribo Life Science Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following criteria are met: 1. Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent. 2. Male and female subjects, aged 18 to 65 years (inclusive). 3. Body mass index between 18 and 32 kg/m2, inclusive. 4. Fasting TG ≥ 0.9 mmol/L (80 mg/dL) and ≤ 3.4 mmol/L (300 mg/dL) at screening. 5. Fasting LDL-C \< 4.9 mmol/L (\<190 mg/dL) at screening. 6. Healthy as determined by pre-study medical history, physical examination, clinical laboratory assessments, and 12-lead electrocardiogram (ECG). 7. Satisfy one of the following: * Females: must be non-pregnant and non-lactating; surgically sterile, post-menopausal, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is using an acceptable contraceptive method (refer to Section 4.6.3) for four weeks before, during, and for at least 6 months after the last dose of study drug administration. * Males: must be surgically sterile, abstinent, or if engaged in sexual relations of child-bearing potential, the subject is utilizing an acceptable contraceptive method (refer to Section 4.6.3)) during and for at least 6 months after the last dose of study drug administration. 8. Non-smokers and non-nicotine users for at least 90 days before screening
Exclusion criteria
A subject meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0 | SAD: Up to 24 weeks; MAD: Up to 28 weeks | The investigator will make an assessment of intensity for each AE and SAE reported during the study according to CTCAE V5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the pharmacokinetic parameter Tmax of RBD5044 in healthy subjects | 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 | Time to maximum concentration (Tmax) |
| To characterize the pharmacokinetic parameter AUC0-inf of RBD5044 in healthy subjects | 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 | Area under the concentration-time curve from 0 to infinity (inf) (AUC0-inf) |
| To characterize the pharmacokinetic parameter AUC0-t of RBD5044 in healthy subjects | 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 | Area under the concentration-time curve from 0 to the collection time t (AUC0-t) |
| To characterize the pharmacokinetic parameter t1/2 of RBD5044 in healthy subjects | 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 | Plasma Half-Life (t1/2) |
| To characterize the pharmacokinetic parameter λz of RBD5044 in healthy subjects | 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 | Terminal rate constant (λz) |
| To characterize the pharmacokinetic parameter Cmax of RBD5044 in healthy subjects | 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 | Plasma Maximum concentration (Cmax) |
| To characterize the pharmacokinetic parameter CL/F of RBD5044 in healthy subjects | 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 | Oral clearance (CL/F) |
| To characterize the pharmacokinetic parameter Vz/F of RBD5044 in healthy subjects | 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 | Volume of distribution in the terminal elimination period (Vz/F) |
| To evaluate the pharmacodynamics (PD) effect of RBD5044 on serum levels of APOC3 in healthy subjects | SAD: Up to 24 weeks; MAD: Up to 28 weeks | by testing Concentrations of APOC3 |
| To evaluate the PD effect of RBD5044 on serum levels of triglyceride (TG) in healthy subjects. | SAD: Up to 24 weeks; MAD: Up to 28 weeks | by testing Concentrations of TG |
| To characterize the pharmacokinetic parameter MRT of RBD5044 in healthy subjects | 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 | mean residence time (MRT) |
Countries
Australia
Outcome results
None listed