A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profiles of Y-3 in Healthy Adult Volunteers in the United States
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Evaluate the Cmax of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin
研究概览
简要总结
The goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetic profiles of Y-3 in healthy adult volunteers in the United States. The main questions it aims to answer are:
- What the pharmacokinetic profiles of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers?
- If drug Y-3 (40mg and 60 mg) is safe and tolerate in the US healthy adult volunteers.
Researchers will compare drug Y-3 (40 mg and 60 mg) to a placebo (a look-alike substance that contains no drug) to see what the pharmacokinetic profiles of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers and if drug Y-3 (40mg and 60 mg) is safe and tolerate in the US healthy adult volunteers.
Participants will:
- Take drug Y-3 (40 mg) or Y-3 (60 mg) or a placebo only once.
- Answer questions regarding your medical history.
- Comply with the study procedures and requests.
- Complete all tests and collections of PK Sampling.
- Must not have any special dietary requirements and be able to consume the food (low-fat) provided by Tranquil Clinical Research during your 4-night stay.
- Must avoid excessive ( > 8 cups per day) caffeine consumption (i.e. coffee or tea) during your time in the study.
- Must not consume any food or beverage rich in grapefruit, papaya, or mango during your time in the study.
- Must not take any other medications, including traditional Chinese medicines and herbal medicines, during your time in the study.
- Must avoid sexual activity or use non-drug contraceptive measures (i.e. condoms) during your time in the study.
- Female participants must not become pregnant while in the study.
- Must not receive any vaccinations during your time in the study.
- Must not donate blood for purposes outside of study procedures during your time in the study.
- Must not drink alcohol during your time in the study.
- Must not smoke during your time in the study.
- Inform your Study Doctor if you no longer wish to participate in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
CRA, sponsor，CRO
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Medically documented as healthy at the time of screening as determined by their medical history, medical assessment, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests, etc.
- •Within 18-45 years at the time of informed consent, inclusive.
- •Body weight ≥ 50 kg for male and ≥ 45 kg for female, body mass index (BMI) within the range of 19 - 28 kg/m2, inclusive.
- •Fully understand and provide a signed informed consent before performing any study-related procedures.
- •Comply with the study and follow-up procedures.
排除标准
- •Known allergy to Y-3 or any of its excipients.
- •Have disease history or current disease that may affect the safety evaluation of the subject or the internal process of the study drug, that the investigator judged to be of clinical significance, including the cardiovascular system, endocrine system, central nervous system, digestive system, respiratory system, hematological system, immunology, psychiatry, metabolic abnormalities, etc.
- •Clinically significant abnormal 12-lead electrocardiograms (ECG) and vital signs judged by the investigator.
- •Clinically significant abnormal laboratory tests (hematology, serum chemistry, coagulation, urinalysis, etc.) and other screening tests judged by the investigator.
- •Test positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, syphilis antibody or human immunodeficiency virus (HIV) antibody.
- •Alcoholics or regular drinkers within 6 months prior to screening, that is, those who drink more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of alcohol with 40% alcohol content or 150 mL of wine), or whose alcohol breath test results are greater than 0.0 mg/100 mL, or who cannot abstain from alcohol during the study.
- •Smokers, that is, those who smoke more than 3 cigarettes per day within 3 months prior to screening, or those who cannot comply with the prohibition of smoking during the study.
- •Current or former drug users, or positive urine screen for drugs of abuse at screening.
- •Have special requirements for diet and cannot follow the unified diet.
- •Drink too much tea, coffee and/or caffeine-containing beverages (more than 8 cups, 1 cup = 250 mL) every day within 3 months prior to screening, or who have consumed any diet (food or beverage) rich in grapefruit, pitaya and mango within 14 days prior to screening.
- •Have taken any prescription drug or over-the-counter drug, traditional Chinese medicine or herbal medicine, health products within 14 days prior to screening, or 5 half-lives, whichever is longer, before the first dose of study drug, or have received vaccine inoculation within 14 days prior to screening; or plan to inoculate vaccine during the study.
- •Participated in any other clinical trials within 3 months prior to screening.
- •Donation or loss of blood equal to or in excess of 200 mL within 3 months prior to screening.
- •Female subjects who have unprotected intercourse within 14 days prior to screening, or pregnant or lactating women.
- •Male subjects (or their partners) or female subjects have baby plans during the whole trial period and within 3 months after the end of the trial, or subjects are unwilling to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, ligation, etc.) during the study.
- •Subjects voluntarily withdraw from the study due to personal reason, or subjects who the investigator believes are not suitable for enrollment for other reasons.
- •Suicidal ideation, history of suicidal behavior, or history of psychiatric comorbidities.
研究组 & 干预措施
Y-3 for injection (Y-3)
The investigational drug (Y-3) consists of two parts: Y-3 for injection (lyophilized powder) （20 mg）and Solvent for Y-3 for injection (concentrated solution)（3ml (containing 0.6 g propylene glycol)）.
Subjects will receive Y-3 or placebo on the morning of the dosing day. Drinking water is prohibited from 1 hour before administration until the end of dosing, and subjects may have meals 4 hours after administration.
Using a sterile syringe, withdraw dedicated solution into the lyophilized powder vial of Y-3 or placebo. Shake the vial manually until the powder is dissolved. Once completely dissolved, use a sterile syringe to transfer the solution into the infusion bottle (normal saline) and gently mix by swirling. The intravenous infusion volume is 250 ml, and infusion time is 60 min ± 10 min. The storage time of the reconstituted drug product or placebo should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature prior to initiation of administration.
干预措施: Y-3 for injection (Drug)
placebo
The placebo consists of two parts: placebo (lyophilized powder) and Solvent for Y-3 for injection(concentrated solution).
Subjects will receive Y-3 or placebo on the morning of the dosing day. Drinking water is prohibited from 1 hour before administration until the end of dosing, and subjects may have meals 4 hours after administration.
Using a sterile syringe, withdraw dedicated solution into the lyophilized powder vial of Y-3 or placebo. Shake the vial manually until the powder is dissolved. Once completely dissolved, use a sterile syringe to transfer the solution into the infusion bottle (normal saline) and gently mix by swirling. The intravenous infusion volume is 250 ml, and infusion time is 60 min ± 10 min. The storage time of the reconstituted drug product or placebo should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature prior to initiation of administration.
干预措施: Placebo (Drug)
结局指标
主要结局
Evaluate the Cmax of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin
时间窗: treatment period (Day1-Day4)
Maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data.
Evaluate the AUC 0-t of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. Calculated according to linearity trapezoidal rule: AUC (i, i+1) = (Ti+1-Ti) (Ci+Ci+1) /2, and AUC0-t is the sum of all AUC (i, i + 1).
Evaluate the AUC 0-∞ of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Area under the concentration-time curve from time 0 to infinity (extrapolated). AUC 0-∞ =AUC 0-t + Ct/λz (Ct is the last measured plasma concentration).
Evaluate the Tmax of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Time to reach maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data.
Evaluate the t1/2 of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Terminal elimination half-life. t1/2 = ln2/λ。
Evaluate the λz of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Terminal-phase elimination rate constant, slope of curves terminal segment at semi-log concentration-time curve calculated by linear regression.
Evaluate the AUC_%Extrap of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
The percentage of the AUC0-inf that has been extrapolated. AUC\_%Extrap = \[(AUC0-∞-AUC0-t)/AUC0-∞\] × 100%
Evaluate the Vz of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Volume of distribution. Vz = Div/AUC0-∞/λz
Evaluate the CL of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Total body clearance. CLz = Div /AUC0-∞
Evaluate the MRT 0-t of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Mean residence time within the time from time zero to the lowest testing plasma concentration. MRT0-t = AUMC0-t/AUC0-t.
Evaluate the MRT 0-∞ of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by venous blood and Phoenix WinNonlin.
时间窗: treatment period (Day1-Day4)
Mean residence time extrapolated from zero to infinity. MRT 0-∞ = AUMC 0-∞/AUC 0-∞.
次要结局
- Evaluate the safety of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of physical examinations after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the safety of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of vital signs after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the tolerability of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of physical examinations after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the tolerability of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of vital signs after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the tolerability of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by the rates of adverse events after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the safety of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of 12-lead ECG after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the safety of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of laboratory tests after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the safety of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by the rates of adverse events after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the tolerability of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of 12-lead ECG after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)
- Evaluate the tolerability of single ascending doses of Y-3 (40 mg and 60 mg) in the US healthy adult volunteers by Incidence of subject getting abnormal results of laboratory tests after treatment.(This study comprises a screening period (Day -14 to Day -2), a baseline period (Day -1), a treatment period (Day1 - Day4), and a safety follow-up period (Day7).)