A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Clinical Study on the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of RAB001 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Adverse events
研究概览
简要总结
This trial is a single center, randomized, double-blind, placebo-controlled dose escalation study aimed at examining the safety, tolerability, and pharmacokinetics/pharmacodynamics of single and multiple injections of RAB001 in healthy subjects.
According to the results of Phase I clinical trials abroad, two dose groups (400 μ g/kg and 750 μ g/kg) were established, with 8 healthy subjects enrolled in each dose group (6 in the experimental group and 2 in the placebo group), for a total of 16 healthy subjects. Each dose group is divided into two stages.
Phase 1: Single dose administration phase Subjects who meet the inclusion criteria will first undergo a single dose study in the 400 μ g/kg dose group. Blood samples will be collected at predetermined time points for single dose PK, PD, and immunogenicity evaluation. After the single dose, safety and tolerance data will be collected for 14 days. If the subjects are tolerant, a single dose study in the 750 μ g/kg dose group can be conducted. After the dose increases to the maximum dose of 750 μ g/kg as designed in this experiment, the next dose will not be administered.
Phase 2: Multiple administration phase Single dose administration is combined with multiple dose administration. If the subjects can tolerate it during the single dose phase, they will enter the multiple dose study phase, which will be administered once every 2 weeks, on days 15, 29, and 43 respectively. Collect blood samples at predetermined time points for PK, PD, and immunogenicity evaluation, observe for 14 days after the last administration, and collect safety and tolerability data.
This experiment adopts a step-by-step increasing method for dose escalation, and the next dose group must complete the safety and tolerability evaluation of a single dose in the previous dose group before starting. Each subject only receives one corresponding dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male body weight should be at least 50.0 kg, female body weight should be at least 45 kg; body mass index (BMI) should be between 19.0-26.0 kg/m2 (including boundary values);
- •Can understand the informed consent form, voluntarily participate and sign the informed consent form;
- •Capable of completing experiments in accordance with the research protocol.
排除标准
- •During the screening period, vital signs, physical examination, 12 lead electrocardiogram examination, and laboratory tests (including blood routine, urine routine, blood biochemistry, and coagulation function) were determined by the researchers to be clinically significant abnormalities;
- •Suffering from the blood system, circulatory system, and digestive system Individuals with a history of serious clinical diseases such as systemic, urinary, respiratory, nervous, immune, endocrine, malignant tumors, mental disorders, and metabolic abnormalities, or any other diseases or physiological conditions that can interfere with test results;
- •Individuals with a significant history of allergic reactions in clinical practice, especially drug allergies, or those known to be allergic to this product;
- •Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody and treponema pallidum (TP) antibody test, any of which is positive;
- •Individuals with positive urine screening for drug abuse (including morphine, methamphetamine, ketamine, methylenedioxymethamphetamine, tetrahydrocannabinol);
- •Individuals with a history of drug use or substance abuse (including the use of prohibited substances for medical use and controlled drugs);
- •Screening for those who have undergone critical surgery within the previous 3 months or plan to undergo surgery during the trial period, as well as those who have undergone surgery that may affect drug absorption, distribution, metabolism, and excretion;
- •Screening participants who have participated in any clinical trial as subjects within the first 3 months;
- •Individuals who have donated blood or lost blood/plasma greater than 400 mL within the first 3 months of screening (excluding female physiological bleeding);
- •Alcoholics (i.e. males drinking more than 28 standard units of alcohol per week and females drinking more than 21 standard units of alcohol per week, with 1 standard unit containing 14 g of alcohol, such as 360 mL of beer or 45 mL of 40% spirits or 150 mL of wine) or those who have frequently consumed alcohol (i.e. drinking more than 14 standard units of alcohol per week) within the 6 months prior to screening, or those who cannot abstain from alcohol during the trial period, or those who have a positive breathalyzer test;
- •Individuals who have taken any prescription or over-the-counter drugs, as well as any functional vitamins or herbal products within the 14 days prior to screening;
- •Those who have consumed excessive amounts of tea, coffee, or caffeinated beverages for a long time in the past (8 or more cups per day, 1 cup=250 mL);
- •It cannot be guaranteed that vigorous exercise, smoking, and special diets (including grapefruit, chocolate, tea, cola, or any caffeinated food or beverage, alcoholic beverage, or other food or beverage that affects drug absorption, distribution, metabolism, or excretion) will be prohibited from 48 hours before administration until the last blood collection;
- •Pregnant or lactating women, or female subjects who have had unprotected sex within two weeks prior to screening, or female subjects who have a positive blood pregnancy test; Female and male participants (or their partners) who have had fertility plans or donated sperm/eggs throughout the entire trial period and within 6 months after the end of the study, and who are unwilling to use one or more contraceptive measures during the trial period and within 6 months after the end of the study;
- •Those who cannot tolerate venipuncture or difficulty in venous blood collection;
- •Individuals with a history of fainting from needles or blood, or known severe bleeding tendencies;
- •Those who have special dietary requirements and cannot follow a uniform diet;
- •The researchers believe that there are any circumstances that may affect the provision of informed consent or adherence to the trial protocol by the subjects, or that the participation of the subjects in the trial may affect the trial results or their own safety.
研究组 & 干预措施
experimental group
The subjects received intravenous administration of RAB001
干预措施: RAB001 750 μg/kg group (Drug)
Control group
The subjects received intravenous administration of normal saline
干预措施: Normal saline (Drug)
experimental group
The subjects received intravenous administration of RAB001
干预措施: RAB001 400 μg/kg group (Drug)
结局指标
主要结局
Adverse events
时间窗: 14 days after single injections
Adverse events,evaluate the safety of single injections of RAB001 at different doses
Serious adverse events
时间窗: 14 days after single administration
serious adverse events during the study
Adverse events
时间窗: 14 days after multiple administrations
Adverse events evaluate the safety and tolerability of multiple injections of RAB001 at different doses
Serious adverse events
时间窗: 14 days after multiple administrations
Serious adverse events during the study，evaluate the safety of multiple injections of RAB001 at different doses
次要结局
- PK parameter Cmax(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15)
- PK parameter AUC0-t(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter AUC0-∞(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter Tmax(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter T1/2z(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter-Vz/F(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter-CL(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK parameter λz(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- PK Parameter: CLss(The 0-24 hours after dosing on Day 1 and the 0-24 hours after dosing on Day 15.)
- Bone turnover marker: BALP(Day 1、8 、15、29、43 、 57)
- Bone turnover marker: PINP levels(Day 1、8 、15、29、43 、57)
- Bone turnover marker: Osteocalcin (OC) Levels(Day 1、8 、15、29、43 、 57)
- Bone turnover marker:CTX-I Levels(Day 1、8 、15、29、43 、57)
- Bone turnover marker: VEGF(Day 1、8 、15、29、43、57)