A Pharmacokinetic Study of HS-10504 in Participants With Hepatic Impairment and Normal Hepatic Function.
This is a two-part single-center, open-label, parallel, single-dose pharmacokinetic study of HS-10504 in participants with hepatic impairment and normal hepatic function.
研究概览
地位
干预/治疗
详细说明
In each part, two treatment groups were set up (Group A: participants with moderate hepatic impairment; Group B: participants with normal hepatic function), and 8 participants (both males and females) were enrolled in each group. On Day 1, a single oral dose of 400 mg HS-10504 tablet was administered in the fasting state.
研究类型
注册 (估计的)
阶段
- 阶段1
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
-
All participants must meet ALL of the following criteria to be eligible for this study:
- Provide written informed consent before any study related procedures, have a full understanding of the study, its procedures, and possible adverse events, and express a willingness and ability to comply with the protocol requirements.
- Be male or female adults.
- Agree to practice highly effective contraception from the time of signing the informed consent form until 6 months after the last dose of study drug (only non pharmacological contraceptive measures are allowed during the study), and refrain from attempting to conceive or donate sperm/eggs during this period.
Participants with normal hepatic function must meet the following criterion to be eligible for this study:
1. Participants in the normal hepatic function group should be matched with those in the hepatic impairment group for body mass index (BMI), age, and sex.
Participants with hepatic impairment must meet the following criteria to be eligible for this study:
- Chronic liver injury caused by primary liver disease;
- The investigator judges that the participant's hepatic function status is stable based on the participant's clinical symptoms and other available examination results at screening;
- Have had a stable medication regimen for the treatment of hepatic impairment, complications, and other concomitant diseases for at least 14 days prior to administration of the investigational product, with no need for dose adjustment; or have not been on any such medication.
Exclusion Criteria:
-
Participants who meet any of the following criteria will not be enrolled in this study:
- Have participated in any other clinical trial and used any investigational drug/device within 3 months prior to screening;
- Have a history of surgery within 3 months prior to screening, or have planned surgery during the study period, or have undergone surgery that may affect drug absorption, distribution, metabolism, or excretion;
- Have experienced significant blood loss or blood donation within 3 months prior to screening, or blood loss ≥200 mL within 1 month, or have planned blood donation during the study period;
- Have used strong or moderate inhibitors or inducers of CYP3A4/5, CYP2C8, and CYP2D6 within 30 days prior to the first dose of the investigational product, or have used albumin within 14 days prior to the first dose;
- Have a history of, or currently have, severe diseases of the nervous, psychiatric, digestive, circulatory, respiratory, urinary systems, etc., or have developed a new illness before administration of the investigational product, which is assessed by the investigator as unsuitable for participation in this study;
- Have a history of severe allergy, are prone to allergic reactions, or have an allergic constitution, or are known to be allergic to any component of the investigational product;
- Have regularly consumed alcohol within 3 months prior to screening or are unable to refrain from alcohol consumption during the study period, or have a positive alcohol breath test at screening;
- Have smoked an average of >5 cigarettes per day within 3 months prior to screening, or are unable to refrain from using any tobacco products during the study period;
- Have consumed excessive amounts of tea, coffee, and/or caffeinated beverages within 3 months prior to screening;
- Have a history of drug abuse, drug dependence, or illicit drug use within 5 years prior to screening, or have a positive drug abuse screening test;
- Are lactating women within 1 month prior to screening or during the study period, or have a positive pregnancy test;
- Have had unprotected sexual intercourse within 14 days prior to screening;
- Have special dietary requirements, are unable to comply with a uniform diet, or have difficulty swallowing;
- Are unable to tolerate venipuncture or indwelling needle blood sampling, or have a history of needle phobia or blood phobia;
- Are unable to complete the study for other reasons, or are judged by the investigator as unsuitable for participation.
Participants with normal hepatic function who meet any of the following exclusion criteria will be excluded:
- History of hepatic impairment;
- Clinically significant abnormalities in physical examination, vital signs, 12 lead ECG, or clinical laboratory tests at screening that are judged by the investigator as unsuitable for enrollment;
- Use of any prescription drugs, over the counter drugs, herbal medicines, or health supplements within 14 days prior to the first dose of the investigational product, or use of any drug without a washout period of at least 7 half lives.
Participants with hepatic impairment who meet any of the following exclusion criteria will be excluded:
- The participant has any of the following conditions that, in the investigator's assessment, makes them unsuitable for participation in this trial: ① history of liver transplantation; ② history of partial hepatectomy; ③ suspected or confirmed hepatocellular carcinoma or other malignancies; ④ hepatic failure; ⑤ bleeding from esophageal and gastric varices within 3 months prior to screening; ⑥ diseases such as biliary cirrhosis or extrahepatic biliary obstruction; ⑦ coexisting overt hepatic encephalopathy, refractory ascites, or hepatorenal syndrome.
- Apart from the primary liver disease itself, the participant has a history of or currently has other severe systemic organ diseases or clinically significant laboratory abnormalities that, in the investigator's judgment, make them unsuitable for participation in this trial.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:肝功能正常的参与者
|
HS-10504:On Day 1, a single oral dose of 400 mg HS-10504 tablet was administered in the fasting state. |
|
实验性的:Participants with hepatic impairment
|
HS-10504:On Day 1, a single oral dose of 400 mg HS-10504 tablet was administered in the fasting state. |
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 |
|---|---|---|
|
Evaluation of PK parameters of HS-10504: Cmax
大体时间:216 hours after administration of HS-10504
|
To evaluate the Cmax of HS-10504 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504: AUC0-t
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-t of HS-10504 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504: AUC0-∞
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-∞ of HS-10504 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: Cmax.
大体时间:216 hours after administration of HS-10504
|
To evaluate the Cmax of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: AUC0-t.
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-t of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: AUC0-∞.
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-∞ of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: Tmax.
大体时间:216 hours after administration of HS-10504
|
To evaluate the Tmax of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: t1/2z.
大体时间:216 hours after administration of HS-10504
|
To evaluate the t1/2z of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: λz.
大体时间:216 hours after administration of HS-10504
|
To evaluate the λz of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: CL/F.
大体时间:216 hours after administration of HS-10504
|
To evaluate the CL/F of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: Vz/F.
大体时间:216 hours after administration of HS-10504
|
To evaluate the Vz/F of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: MRT0-t.
大体时间:216 hours after administration of HS-10504
|
To evaluate the MRT0-t of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: MRT0-∞
大体时间:216 hours after administration of HS-10504
|
To evaluate the MRT0-∞ of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: fu.
大体时间:216 hours after administration of HS-10504
|
To evaluate the fu of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: Cmax,Unbound.
大体时间:216 hours after administration of HS-10504
|
To evaluate the Cmax,Unbound of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: AUC0-t,Unbound.
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-t,Unbound of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2: AUC0-∞,Unbound.
大体时间:216 hours after administration of HS-10504
|
To evaluate the AUC0-t,Unbound of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Evaluation of PK parameters of HS-10504 and metabolite M6-2:CL/F,Unbound .
大体时间:216 hours after administration of HS-10504
|
To evaluate the CL/F,Unbound of HS-10504 and metabolite M6-2 in participants with hepatic impairment and normal hepatic function |
216 hours after administration of HS-10504
|
|
Adverse events
大体时间:Up to end of the study, approximately 3 months.
|
To evaluate the Occurrence of adverse events |
Up to end of the study, approximately 3 months.
|
|
vital signs(blood pressure)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the vital signs(blood pressure) of HS-10504 in participants with hepatic impairment and normal hepatic function |
Up to end of the study, approximately 3 month.
|
|
vital signs( Pulse)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the vital signs(Pulse) of HS-10504 in participants with hepatic impairment and normal hepatic function |
Up to end of the study, approximately 3 month.
|
|
vital signs(body temperature)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the vital signs( body temperature) of HS-10504 in participants with hepatic impairment and normal hepatic function |
Up to end of the study, approximately 3 month.
|
|
Number of participants with clinical laboratory tests(complete blood count (CBC))
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the clinical laboratory tests(complete blood count (CBC)) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with urinalysis
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of urinalysis of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal blood chemistry
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of blood chemistry of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal coagulation tests
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of coagulation tests of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
12-lead electrocardiogram( heart rate)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the 12-lead electrocardiogram(heart rate) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
12-lead electrocardiogram(PR)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the 12-lead electrocardiogram(PR) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
12-lead electrocardiogram(RR)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the 12-lead electrocardiogram(RR) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
12-lead electrocardiogram(QRS duration)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the 12-lead electrocardiogram(QRS duration) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
12-lead electrocardiogram(QTcF)
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the 12-lead electrocardiogram( QTcF) of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal general inspection
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of general inspection of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal head and neck
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of head and neck of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal lymph nodes
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of lymph nodes of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal chest
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of chest of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal abdomen
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of abdomen of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal spine and extremities
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of spine and extremities of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
|
Number of participants with abnormal neurological examination
大体时间:Up to end of the study, approximately 3 month.
|
To evaluate the abnormal of neurological examination of HS-10504 in participants with hepatic impairment and normal hepatic function. |
Up to end of the study, approximately 3 month.
|
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
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