Hyperlipemia
Conditions
Brief summary
This is a randomized, single blind, placebo controlled, single center phase I study to evaluate the safety, tolerability, pharmacokinetics, and preliminary pharmacodynamics of single and multiple ascending doses of subcutaneously administered RBD7022 in participants with normal or elevated LDL-c cholesterol. The study will be performed in 2 phases: single ascending dose (SAD) phase and multiple ascending doses (MAD) phase in participants. The decision to escalate to subsequent dose levels will be made by the SRC based on the review of all available safety information in each cohort.
Interventions
DRUGRBD7022
Subcutaneously Administered RBD7022 in Healthy Subjects.
DRUGPlacebo
Subcutaneously Administered Placebo in Healthys Subject.
Sponsors
Suzhou Ribo Life Science Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female subjects, aged 18 to 65 years, inclusive * Body mass index between 17 and 28 kg/m2 , inclusive * LDL-C normal or elevated at screening and baseline. * Willing to comply with protocol required visit schedule and visit requirements and provide written informed consent. * The clinical laboratory examination of the subjects was within the normal range, or abnormal but had no clinical significance as judged by the investigators, and did not affect the study results; * Vital signs, physical examination, ECG, ultrasound showed normal or abnormal but no clinically significant as determined by the investigator.
Exclusion criteria
* With a clear history of primary diseases of major organs, the subject is not suitable to participate in this study considered by the investigator; * Diagnosis of diabetes mellitus; * Pregnant or breastfeeding women; * Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v5.0 | SAD up to Day 180; MAD up to Day 208 | By the examination of vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory examination, 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 |
|---|---|---|
| The serum PCSK9 level after subject dosing RBD7022 | SAD up to Day 180; MAD up to Day 208 | measure the pcsk9 level in blood by lab examination and eveluate the effect of RBD7022 on Circulating PCSK9 Levels (Determination of % Lowering of PCSK9 to treatment/Baseline PCSK9 Level). |
| Other blood lipoprotein and lipid parameters besides LDL-c | SAD up to Day 180; MAD up to Day 208 | measure other blood lipoprotein and lipid parameters besides LDL-c in blood by lab examination and eveluate % change and absolute change in other lipoprotein and lipid parameters（TC、TG、Lp (a)、HDL-C、non HDL-C、Apo B、Apo A1、Apo A 1/ Apo B ratio） from baseline up to Day 208 |
| The effect of RBD7022 monotherapy or RBD7022 combination with statin in patients with elevated LDL-C | SAD up to Day 180; MAD up to Day 208 | measure the LDL-C and pcsk9 level in blood by lab examination and assess % change and absolute change in LDL-c and PCSK9 from baseline up to Day 208 |
| To characterize the pharmacokinetic parameter Cmax | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Plasma Maximum concentration (Cmax) |
| To characterize the pharmacokinetic parameter Tmax | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Time to maximum concentration (Tmax) |
| The serum LDL-C level after subject dosing RBD7022 | SAD up to Day 180; MAD up to Day 208 | measure the LDL-C level in blood by lab examination and eveluate the effect of RBD7022 on Circulating LDL-c Levels (Determination of % Lowering of LDL-c to treatment/Baseline LDL-c Level) |
| To characterize the pharmacokinetic parameter t1/2 | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Half-Life (t1/2) |
| To characterize the pharmacokinetic parameter λz | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Elimination rate constant (λz) |
| To characterize the pharmacokinetic parameter CL/F | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Oral clearance (CL/F) |
| To characterize the pharmacokinetic parameter Vz/F | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Volume of distribution in the terminal elimination period (Vz/F) |
| To characterize the pharmacokinetic parameter AUC0-inf | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Area under the concentration-time curve from 0 to infinity |
| To characterize the pharmacokinetic parameter AUC0-t | SAD: within 60 min before dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24, 48 and 72 hours after dosing; MAD: within 60 minutes before day 0 and day 28 dosing, and at 15min, 30min, 1, 2, 4, 6, 8,12, 24 ,48 and 72 hours after Day 0 and day 28 dosing | Area under the concentration-time curve from 0 to the collection time t (AUC0-t) |
Countries
China
Outcome results
None listed