A Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of KR23248 Capsules in Healthy Adult Subjects
A Randomized, Double-blind, Placebo-controlled, Dose-escalating Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of Single and Multiple Doses of KR23248 Capsules in Healthy Adult Subjects
研究概览
详细说明
This study is a randomized, double-blind, placebo-controlled, dose-escalating Phase I trial, aiming to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of single and multiple oral doses of KR23248 capsules in healthy adult subjects. The study consists of two parts: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) studies.
The single ascending dose study plans to enroll 54 healthy subjects, with predefined dose escalation levels of 0.5 mg, 1.0 mg, 2.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg in sequence. The multiple ascending dose study sets the initial dose at 2.0 mg, with 12 healthy subjects planned for enrollment.
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名:Huafang Li
- 电话号码:+8618017311256
- 邮箱:lhlh_5@163.com
研究联系人备份
- 姓名:Yan Li
- 电话号码:+8613046600636
- 邮箱:liyan7721@163.com
参与标准
资格标准
适合学习的年龄
- 成人
接受健康志愿者
描述
Inclusion Criteria:
- Healthy male/female subjects aged ≥ 18 years and ≤ 45 years (inclusive) at the time of signing the informed consent form.
- Body Mass Index (BMI) ranging from 18.5 to 28.0 kg/m² (inclusive) at screening; male subjects with body weight ≥50 kg and female subjects with body weight ≥45 kg.
- Subjects who voluntarily participate in the trial and sign the informed consent form after understanding the purpose, content, procedures, and potential risks of the trial.
- Subjects who can communicate well with the investigators, are willing and able to comply with lifestyle restrictions specified in the protocol, and cooperate with study procedures.
Exclusion Criteria:
- Subjects with any diseases or dysfunctions in present illness and medical history that may interfere with the clinical trial, including but not limited to neurological and psychiatric diseases, cardiovascular diseases (e.g., congenital long QT syndrome), urinary system disorders, digestive system disorders, respiratory system disorders, musculoskeletal system disorders, metabolic and endocrine system disorders, skin diseases, hematological diseases, immune system diseases, and tumors.
- Subjects with any surgical condition or medical history that may significantly affect drug absorption, distribution, metabolism and excretion, or may pose a risk to the subject participating in the trial; such as a history of gastrointestinal surgery (gastrectomy, gastroenterostomy, enterectomy, etc.), urinary tract obstruction or dysuria, gastroenteritis, peptic ulcer, and history of gastrointestinal bleeding.
- Subjects with a history of severe allergic reactions or known hypersensitivity to any ingredients of the investigational product.
- Subjects with current or previous psychiatric disorders or cerebral dysfunction; those assessed to be at suicide risk based on the Columbia-Suicide Severity Rating Scale (C-SSRS), or by the investigator's clinical assessment, or those with a history of self-harm behavior.
- Subjects with a history of substance abuse within 1 year prior to administration or with a positive urine drug screening result.
- Subjects with a history of alcohol abuse within 6 months prior to screening (i.e., more than 14 standard units per week; 1 standard unit = 360 mL beer, or 45 mL spirits with 40% alcohol content, or 150 mL wine); or with a positive breath alcohol test; or unwilling to abstain from alcohol and any alcohol-containing products from screening until the last PK blood collection.
- Subjects with a history of surgery within 3 months prior to screening, or who have not recovered from surgery, or have a planned surgery scheduled during the trial.
- Subjects who have donated blood or experienced blood loss ≥ 400 mL within 3 months prior to screening, or ≥ 200 mL within one month, or have a history of blood product transfusion.
- Subjects who have participated in any clinical trial and received investigational drugs or medical devices within 3 months prior to screening.
- Subjects who have received vaccination within 30 days prior to screening, or have a vaccination plan during the entire study period.
- Subjects who have taken any medications within 28 days or 5 half-lives (whichever is longer) prior to screening and during the entire study period, including prescription drugs, over-the-counter drugs, herbal medicines, and any drugs that inhibit or induce hepatic drug-metabolizing enzymes (e.g., inducers and/or inhibitors of CYP3A4, CYP2D6, and CYP3A5).
- Female subjects who are pregnant, breastfeeding, or have a positive pregnancy test; or those who refuse to adopt effective non-pharmacological contraceptive measures (e.g., abstinence, intrauterine device, condoms with vaginal spermicide) throughout the study period and within 28 days after the end of administration; or those with a plan to donate sperm or ova.
- Subjects with clinically significant abnormal findings judged by the investigator in comprehensive physical examination, vital signs, laboratory tests and 12-lead electrocardiogram; including but not limited to: QTc > 450 ms in males and > 470 ms in females (Fridericia correction); resting pulse rate < 55 beats/min or > 100 beats/min; systolic blood pressure < 90 mmHg or ≥ 140 mmHg; diastolic blood pressure < 60 mmHg or ≥ 90 mmHg.
- Subjects with non-negative results for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV-Ab), Human Immunodeficiency Virus antibody (HIV-Ab), and Toluidine Red Untreated Serum Test (TRUST).
- Subjects with alanine transaminase (ALT), creatinine (Cr) or serum prolactin level exceeding 2 times the upper limit of normal during the screening period.
- Subjects who smoke an average of ≥ 5 cigarettes per day within 3 months prior to screening, or are unable to abstain from any tobacco products during the trial.
- Subjects with an average daily intake of ≥ 5 cups of coffee or tea (200 mL per cup) within 3 months prior to screening, or are unable to discontinue intake during the trial.
- Subjects with special dietary requirements who cannot follow a unified study diet, or have difficulty in swallowing.
- Subjects who have consumed food or beverages containing grapefruit and/or pomelo within 7 days prior to administration.
- Subjects who have consumed xanthine-rich food or beverages (e.g., tea, coffee, cola, chocolate) within 3 days prior to administration.
- Subjects with poor compliance or other conditions deemed unsuitable for participation in the trial by the investigator.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Part 1 cohort 1
SAD Cohort 1: single oral dose of 0.5mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
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实验性的:Part 1 cohort 2
SAD Cohort 2: single oral dose of 1.0mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
|
实验性的:Part 1 cohort 3
SAD Cohort 3: single oral dose of 2.0mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
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实验性的:Part 1 cohort 4
SAD Cohort 4: single oral dose of 3.0mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
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实验性的:Part 1 cohort 5
SAD Cohort 5: single oral dose of 4.5mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
|
实验性的:Part 1 cohort 6
SAD Cohort 6: single oral dose of 6.0mg KR23248 capsule
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
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安慰剂比较:Part 1 cohort 7
SAD cohort 7: single oral dose of placebo capsule
|
参与者将接受安慰剂
其他名称:
|
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实验性的:Part 2 KR23248 2.0mg
MAD: Multiple oral doses of 2.0mg KR23248 capsules administered once daily for 14 consecutive days
|
Participants will recieve a single oral dose of KR23248
其他名称:
|
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安慰剂比较:Part 2 Placebo
MAD: Multiple oral doses of placebo capsules administered once daily for 14 consecutive days
|
参与者将接受安慰剂
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Incidence of adverse events (AEs), serious adverse events(SAEs), drug-related AEs, and AEs leading to study withdrawal
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
The number and percentage of participants with AEs,SAEs, drug-related AEs, and AEs leading to study withdrawal will be determined
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Cmax
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Maximum Serum Concentration
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
Tmax
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Time to Reach the Maximum Serum Concentration
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
t1/2
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Elimination half-life
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
λz
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Terminal rate constant
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
AUC0-t
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Area under the plasma concentration-time curve from time zero to the last quantifiable concentration
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
AUC0-∞
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Area under the plasma concentration-time curve from time zero extrapolated to infinity
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
CL/F
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Apparent Clearance
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
Vd/F
大体时间:SAD:Day 1 to Day14 MAD:Day1 to Day28
|
Apparent Volume of Distribution
|
SAD:Day 1 to Day14 MAD:Day1 to Day28
|
|
MRT
大体时间:SAD: Day1 to D14 MAD:Day1 to Day28
|
Mean residence time
|
SAD: Day1 to D14 MAD:Day1 to Day28
|
|
Css_min
大体时间:MAD:Day1 to Day28
|
Steady-state trough concentration
|
MAD:Day1 to Day28
|
|
Css_max
大体时间:MAD:Day1 to Day28
|
Steady-state peak concentration
|
MAD:Day1 to Day28
|
|
Tss,max
大体时间:MAD:Day1 to Day28
|
Time to Reach Maximum Concentration at Steady State
|
MAD:Day1 to Day28
|
|
Cavg,ss
大体时间:MAD:Day1 to Day28
|
Average Steady-State Concentration
|
MAD:Day1 to Day28
|
|
DF
大体时间:MAD:Day1 to Day28
|
Fluctuation Percentage
|
MAD:Day1 to Day28
|
|
Rac
大体时间:MAD:Day1 to Day28
|
Accumulation Factor
|
MAD:Day1 to Day28
|
|
AUCss
大体时间:MAD:Day1 to Day28
|
Area under the plasma concentration-time curve over a dosing interval at steady state
|
MAD:Day1 to Day28
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- KR23248-202509
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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