ChiCTR2400092316 版本V1.0 版本创建时间2024/11/14 09:48:59 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2400092316 

最近更新日期：

Date of Last Refreshed on：

 2024-11-14 09:48:53 

注册时间：

Date of Registration：

 2024-11-14 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

盐酸凯普拉生片在肝功能不全人群药代动力学研究

Public title：

Pharmacokinetic study of keplasen hydrochloride tablets in population with hepatic insufficiency.

注册题目简写：

English Acronym：

研究课题的正式科学名称：

单中心、非随机、开放、平行对照设计，评估中度肝功能不全对盐酸凯普拉生片的药代动力学和安全性影响的临床研究

Scientific title：

Evaluation of the effect of moderate hepatic insufficiency on the pharmacokinetics and safety of keplasen hydrochloride tablets: a single-center, non-randomized, open-label, parallel-controlled design clinical trial.

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

姜雅琼 

研究负责人：

陈桂玲/戴霞红 

Applicant：

Yaqiong Jiang 

Study leader：

Guiling Chen/Xiahong Dai 

申请注册联系人电话：

Applicant telephone：

 +86 151 5188 0330

研究负责人电话：

Study leader's
telephone：

+86 183 4311 3893

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 jiangyaqiong@carephar.com

研究负责人电子邮件：

Study leader's E-mail：

 chenguiling707@126.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

江苏省南京市玄武区徐庄路6号

研究负责人通讯地址：

浙江省衢州市柯城区钟楼底2号

Applicant address：

6 Xuzhuang Road, Xuanwu District, Nanjing City, Jiangsu Province, China

Study leader's address：

2 Zhongloudi, Kecheng District, Quzhou City, Zhejiang Province, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

江苏柯菲平医药股份有限公司

Applicant's institution：

Jiangsu Carephar Pharmaceutical Co., Ltd

研究负责人所在单位：

树兰(衢州)医院

Affiliation of the Leader：

Shulan (Quzhou) Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 2024伦审第(9)号

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

树兰（衢州）医院医学伦理管理委员会

Name of the ethic committee：

Shulan (Quzhou) Hospital Medical Ethics Management Committee

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-10-09 00:00:00

伦理委员会联系人：

方菶菶

Contact Name of the ethic committee：

Bengbeng Fang

伦理委员会联系地址：

浙江省衢州市柯城区钟楼底2号

Contact Address of the ethic committee：

2 Zhongloudi, Kecheng District, Quzhou City, Zhejiang Province, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 570 363 6220

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

树兰(衢州)医院

Primary sponsor：

Shulan (Quzhou) Hospital

研究实施负责（组长）单位地址：

浙江省衢州市柯城区钟楼底2号

Primary sponsor's address：

2 Zhongloudi, Kecheng District, Quzhou City, Zhejiang Province, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏省

市(区县)：

南京市

Country：

China

Province：

Jiangsu

City：

Nanjing

单位(医院)：

江苏柯菲平医药股份有限公司

具体地址：

玄武区徐庄路6号1幢

Institution
hospital：

Jiangsu Carephar Pharmaceutical Co., Ltd

Address：

6 Xuzhuang Road, Xuanwu District

经费或物资来源：

江苏柯菲平医药股份有限公司

Source(s) of funding：

Jiangsu Carephar Pharmaceutical Co., Ltd

研究疾病：

反流性食管炎和十二指肠溃疡  

Target disease：

Reflux esophagitis and duodenal ulcers

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 IV期临床试验 

Study phase：

4

研究设计：

非随机对照试验 

Study design：

Non randomized control 

研究目的：

主要目的： 评估中度肝功能不全对盐酸凯普拉生片的药代动力学特征的影响，为肝功能不全患者的合理临床用药提供科学依据。 次要目的： 评估中度肝功能不全对盐酸凯普拉生片的安全性的影响。  

Objectives of Study：

Main Objective: To assess the effect of moderate hepatic insufficiency on the pharmacokinetic parameters of keplasen hydrochloride tablets, in order to provide a scientific basis for rational clinical use in patients with hepatic insufficiency. Secondary Objective: To assess the effect of moderate hepatic insufficiency on the safety of keplason hydrochloride tablets.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1. 受试者充分了解试验目的、内容、过程以及可能发生的不良反应，自愿作为受试者，并在任何试验程序开始前签署知情同意书； 2. 受试者（包括伴侣）同意自签署知情同意书至末次服用试验药物后6个月内无生育计划、无捐精或捐卵计划，且自愿采取有效避孕措施； 3. 受试者能够和研究者进行良好的沟通，并且理解和遵守本试验的各项要求； 4. 年龄在18~75周岁（含边界值）； 5. 筛选时男性受试者体重≥50kg，女性受试者体重≥45kg，体重指数（BMI）在18.0~30.0kg/m2范围内（含边界值），BMI=体重（kg）/身高2（m2）； 6. 肝功能正常受试者，还需符合以下入选标准：筛选时经各项检查（包括生命体征、体格检查、血常规、尿常规、血生化、凝血功能四项、12-导联心电图、胸部正位X片、腹部彩超等），检查结果正常，或异常但经研究者判断无临床意义； 7. 肝功能不全受试者，还需符合以下入选标准： 1) 筛选前14天内未使用过白蛋白； 2) 乙型病毒性肝炎、丙型病毒性肝炎、酒精性肝病、自身免疫性肝病、非酒精性脂肪性肝病以及遗传代谢性肝病导致（药物性肝损伤患者除外）的肝功能不全，Child-Pugh分级为B级； 3) 通过既往病史、实验室检查或影像学检查确诊为稳定（≥1个月）的肝功能不全； 4) 除判断为肝功能不全诊断的疾病及并发症外，筛选时经各项检查（包括生命体征、体格检查、血常规、尿常规、血生化、凝血功能四项、12-导联心电图、胸部正位X片、腹部彩超等），检查结果经研究者判断身体状态良好，无其他临床显著性异常。

Inclusion criteria

1. subjects fully understands the purpose, content, process and possible adverse effects of the test, volunteer to be subjects and sign the informed consent form prior to the commencement of any trial procedure; 2. subjects (including partner) are willing to have no birth plan, no sperm or egg donation plan, and voluntarily use effective contraception from the time of signing the informed consent to 6 months after the last administration of the test drug; 3. subjects are able to communicate well with investigators and understand and comply with the requirements of the trial; 4. subjects are aged between 18 and 75 years (including borderline values); 5. weight ≥50kg for men and ≥45kg for women at screening; body mass index (BMI) within the range of 18.0-30.0 kg/m2 (including borderline values), BMI = weight (kg)/height2 (m2); 6. subjects with normal liver function must also meet the following inclusion criteria: normal results or abnormal but not clinically significant in the judgment of investigators after all examinations (including vital signs, physical examination, blood routine, urine routine, blood biochemistry, four items of coagulation function, 12-lead electrocardiogram, orthopantomogram of the chest, ultrasound of the abdomen, etc.) at screening; 7. subjects with hepatic insufficiency must also meet the following enrollment criteria: 1) albumin has not been used within 14 days prior to screening; 2) hepatic insufficiency due to viral hepatitis B, viral hepatitis C, alcoholic liver disease, autoimmune liver disease, non-alcoholic fatty liver disease, and inherited metabolic liver disease (except in patients with pharmacologic liver injury), with a Child-Pugh classification of class B; 3) stable (≥1 month) hepatic insufficiency diagnosed by past medical history, laboratory tests or imaging; 4) in addition to the diseases and complications diagnosed as hepatic insufficiency, the results of the screening tests (including vital signs, physical examination, blood, urine, blood biochemistry, coagulation function, 12-lead electrocardiogram, chest X-ray, abdominal ultrasound, etc.), which are judged by the investigator to be in good physical condition with no other clinically significant abnormalities.

排除标准：

1. 对凯普拉生或任意试验用药品组分有过敏史，或过敏体质（多种药物及食物过敏）者，或有特异性变态反应性疾病史（如哮喘、荨麻疹、湿疹性皮炎等）者； 2. 筛选时患有恶性肿瘤，或筛选前5年内有恶性肿瘤病史（治愈稳定2年后的肝癌，已进行治疗且无复发征象的皮肤非黑色素瘤，和已切除的宫颈上皮内瘤变除外）； 3. 现阶段滥用药物；或既往滥用药物；或给药前3个月使用过软毒品（如：大麻）或给药前1年服用硬毒品（如：可卡因、苯丙胺类、苯环己哌啶等）； 4. 现阶段嗜烟；或既往嗜烟；或在筛选前3个月内平均每日吸烟量多于5支；或试验期间无法停止摄取任何烟草类产品者； 5. 现阶段酗酒；或既往酗酒；或筛选前1个月内经常饮酒者（经常饮酒指：女性平均每周饮酒超过14单位酒精，男性平均每周饮酒超过28单位酒精，例如：1单位=360mL啤酒或45mL酒精量为40%的烈酒或150mL葡萄酒）；或试验期间不能禁酒者； 6. 筛选前3个月内献血（包括成分血）或大量失血（≥400mL），或接受输血或使用血制品； 7. 筛选前4周内有严重感染、外伤、胃肠道手术或其他外科大手术者； 8. 计划在试验期间进行手术治疗或有住院倾向者； 9. 筛选前3个月内或试验药物5个半衰期内（取二者中时间较长者）参加过其他临床试验并接受过试验药物者； 10. 筛选前1个月内注射疫苗者； 11. 给药前4周内使用过中草药或CYP450酶强抑制剂或强诱导剂者（CYP450酶强抑制剂或强诱导剂详见附录2）; 12. 给药前14天（或5个半衰期，以时间较长者为准）内服用过任何药物，包括处方药、非处方药、中草药或维生素等保健品者，肝功能不全患者稳定用药除外； 13. 对饮食有特殊要求，试验期间不能接受统一饮食者，或有吞咽困难者； 14. 不能耐受静脉穿刺或晕针、晕血者； 15. 妊娠期或哺乳期女性； 16. 血妊娠检查阳性者； 17. 梅毒螺旋体特异性抗体检测，有临床意义者； 18. 人免疫缺陷病毒（HIV）抗原抗体联合检测，有临床意义者； 19. 给药前48小时内摄入过任何特殊饮食，包括含有葡萄柚汁/西柚汁、甲基黄嘌呤（如茶、咖啡、可乐、巧克力、功能饮料）等食物和/或饮料；或有其他影响药物吸收、分布、代谢、排泄等因素者； 20. 酒精呼气试验结果阳性者； 21. 尿药物滥用筛查阳性者； 22. 研究人员认为依从性差，或有研究者认为不适合参加本试验的其他因素者； 23. 肝功能正常受试者补充排除标准（符合其中1条即排除）： 1) 既往有神经、心血管、血液和淋巴、免疫、肝脏、肾脏、胃肠道、呼吸系统、代谢及骨骼等系统疾病、感染性疾病或重要脏器疾病，经研究者判断不适合参加本试验者； 2) 既往有肝功能不全病史； 3) 筛选前1个月内感染乙肝或丙肝者； 4) 筛选期经实验室检查提示存在和可能存在肝功能不全者； 5) 筛选期乙肝表面抗原定性检测有临床意义，或丙型肝炎病毒（HCV）抗体、丙型肝炎病毒（HCV）核心抗原检测有临床意义者； 24. 肝功能不全受试者补充排除标准（符合其中1条即排除）： 1) 筛选前1周内服用过任何药物，或对肝功能不全和/或其他合并疾病需要长期治疗的未达到至少2周的稳定用药（稳定用药由研究者进行判断）者； 2) 有肝移植史者； 3) 各种原因导致的急性肝功能损伤； 4) 肝衰竭者（采用《肝衰竭诊治指南》2023版标准确诊），合并下列任何一种情况：① 感染；② 3/4级肝性脑病； 5) 肝硬化严重并发症者，合并下列任何一种情况：① 食管胃底静脉曲张破裂活动性出血；② 严重/晚期腹腔积液或胸腔积液需要穿刺引流及补充白蛋白；③ 肝肾综合征等研究者认为不适合参与本试验的受试者； 6) 除判断为肝功能不全诊断的疾病及并发症外，有任何严重疾病史（包括但不仅限于神经、心血管、血液和淋巴、免疫、胃肠道、呼吸系统、代谢及骨骼等系统疾病、感染性疾病或重要脏器疾病史），或研究者认为可能影响试验结果的任何病史； 7) 患有高血压且接受稳定用药后无法降到以下范围内者：收缩压<160mmHg和舒张压<100mmHg； 8) 有活动性乙型肝炎病毒（HBV）及丙型肝炎病毒（HCV）感染者：HBV DNA <500 IU/mL 或<2500 copy/mL、HCV RNA 阴性可入组； 9) 筛选期ALT、AST≥5倍ULN。

Exclusion criteria：

1. subjects have a history of allergy to keplasen or any of the test drug components, or are hypersensitive (multiple drug and food allergies), or have a history of atopic allergic diseases (e.g., asthma, urticaria, eczematous dermatitis, etc.); 2. subjects have a malignant tumor at screening or a history of malignancy within 5 years prior to screening (except for hepatocellular carcinoma 2 years after cure and stabilization, non-melanoma of the skin for which treatment has been administered and there are no signs of recurrence, and resected cervical intraepithelial neoplasia); 3. the subject has abused drugs at the current stage; or has abused drugs in the past; or has used soft drugs (e.g., marijuana) in the 3 months prior to administration of the test drug or has used hard drugs (e.g., cocaine, amphetamines, phenylcyclohexylpiperidines, etc.) in the 1 year prior to administration of the test drug; 4. the subject is addicted to tobacco at the current stage; or was previously addicted to tobacco; or averaged more than 5 cigarettes per day in the 3 months prior to screening; or was unable to stop ingesting any tobacco-based products during the trial; 5. the subject is a current heavy drinker; or a former heavy drinker; or a regular drinker (regular drinker is defined as an average of more than 14 units of alcohol per week for females and more than 28 units of alcohol per week for males, e.g., 1 unit = 360mL of beer or 45mL of 40% alcohol by volume spirits, or 150mL of wine) in the month prior to Screening; or is unable to stop consuming alcohol during the trial; 6. the subject has donated blood (including component blood) or lost a significant amount of blood (≥400mL), or received a blood transfusion or used blood products within 3 months prior to screening; 7. the subject has had a serious infection, trauma, gastrointestinal surgery, or other major surgical procedure within 4 weeks prior to Screening; 8. the subject is undergoing surgical treatment or is predisposed to hospitalization during the planned trial period; 9. the subject has participated in another clinical trial and received the test drug within 3 months or 5 half-lives of the test drug, whichever is longer, prior to Screening; 10. the subject has received a vaccine within 1 month prior to Screening; 11. subjects have used herbs or strong inhibitors or strong inducers of CYP450 enzymes within 4 weeks prior to administration of the test drug; 12. subjects who have taken any medication within 14 days (or 5 half-lives, whichever is longer) prior to taking the test drug, including prescription medications, over-the-counter medications, herbal medications, or health supplements such as vitamins, with the exception of stabilizing medications for patients with hepatic insufficiency; 13. subjects taking test drugs with special dietary requirements, who cannot accept a uniform diet during the trial, or who have difficulty swallowing; 14. subjects can not tolerate venipuncture or needle-sickness, blood-sickness; 15. female subjects are pregnant or breastfeeding; 16. female subjects have a positive blood pregnancy test; 17. subjects' syphilis spirochete-specific antibody test, which were clinically significant; 18. subjects' combined human immunodeficiency virus (HIV) antigen-antibody test are clinically significant; 19. subjects who have ingested any special diet within 48 hours prior to administration of the test drug, including foods and/or beverages containing grapefruit juice/grapefruit juice, methylxanthines (e.g., tea, coffee, cola, chocolate, functional beverages); or other factors that affect the absorption, distribution, metabolism, or excretion of the drug; 20. subjects with a positive alcohol breath test result; 21. subjects have a positive urine drug abuse test result at screening; 22. subjects who, in the opinion of the investigator, are poorly compliant or have other factors that, in the opinion of investigators, make them unsuitable for participation in this trial; 23. additional exclusion criteria for subjects with normal liver function (exclusion if 1 of these is met): 1) subjects with pre-existing neurological, cardiovascular, hematologic and lymphatic, immune, hepatic, renal, gastrointestinal, respiratory, metabolic and skeletal and other systemic diseases, infectious diseases, or diseases of the vital organs that, in the judgment of the Investigator, make participation in the trial unsuitable; 2) subjects have a previous history of hepatic insufficiency; 3) subjects have been infected with hepatitis B or hepatitis C within 1 month prior to screening; 4) subjects have laboratory tests during the screening period that indicate the presence and possible presence of hepatic insufficiency; 5) subjects have a qualitative test for Hepatitis B surface antigen or a clinically significant test for Hepatitis C Virus (HCV) antibodies and Hepatitis C Virus (HCV) core antigen during the screening Period; 24. additional exclusion criteria for subjects with hepatic insufficiency (excluded if 1 of these criteria is met): 1) subjects who have taken any medication within 1 week prior to screening or have not achieved at least 2 weeks of stable medication for hepatic insufficiency and/or other co-morbidities requiring long term treatment (stable medication to be judged by the Investigator); 2) subjects have a history of liver transplantation; 3) subjects with acute hepatic impairment from any cause; 4) subjects with hepatic failure (diagnosed using the criteria of the "Guidelines for the Diagnosis and Management of Liver Failure", 2023 edition) in combination with any of the following: 1) infection; 2) grade 3/4 hepatic encephalopathy; 5) subjects with severe complications of liver cirrhosis, combined with any of the following conditions: (i) active bleeding from ruptured esophagogastric fundic varices; (ii) severe/advanced peritoneal effusion or pleural effusion requiring puncture drainage and albumin supplementation; and (iii) hepatic-renal syndrome, etc., which is considered by the investigator as unsuitable for participation in the trial; 6) subjects have a history of any serious disease (including but not limited to neurological, cardiovascular, hematologic and lymphatic, immunologic, gastrointestinal, respiratory, metabolic and skeletal or other systemic diseases, infectious diseases, or history of diseases of vital organs) in addition to the diseases and complications judged to be diagnostic of hepatic insufficiency or any history of illnesses that, in the opinion of the Investigator, may affect the results of the trial; 7) subjects have hypertension and are unable to reduce it to within the following ranges after receiving stabilizing medication: systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg; 8) subjects with active hepatitis B virus (HBV) and hepatitis C virus (HCV) infection: HBV DNA <500 IU/mL or <2500 copy/mL and HCV RNA negative for enrollment; 9) subjects with ALT and AST ≥ 5 times ULN at screening.

研究实施时间：

Study execute time：

从 From 2024-11-01 00:00:00至 To 2025-11-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-11-15 00:00:00 至 To 2025-10-20 00:00:00

干预措施：

Interventions：

组别：

中度肝功能不全组

样本量：

 8

Group：

Moderate hepatic insufficiency group

Sample size：

干预措施：

空腹单次服用20mg盐酸凯普拉生片

干预措施代码：

Intervention：

A single dose of 20 mg of keplasen hydrochloride tablets in the fasting state

Intervention code：

组别：

肝功能正常组

样本量：

 8

Group：

Normal liver function group

Sample size：

干预措施：

空腹单次服用20mg盐酸凯普拉生片

干预措施代码：

Intervention：

A single dose of 20 mg of keplasen hydrochloride tablets in the fasting state

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 浙江 

市(区县)：

 衢州 

Country：

China

Province：

Zhejiang

City：

Quzhou

单位(医院)：

 树兰(衢州)医院 

单位级别：

 三甲 

Institution
hospital：

Shulan (Quzhou) Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

PK参数

指标类型：

主要指标

Outcome：

PK parameters

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性指标

指标类型：

次要指标

Outcome：

Safety indicators

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

全血

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 75 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

无

Blinding：

None

是否共享原始数据：

IPD sharing

是Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

研究结束后，国家药品监督管理局药品审评中心：https://www.cde.org.cn/

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

After the completion of the study, the Center for Drug Evaluation of the National Medical Products Administration: https://www.cde.org.cn/

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

数据采集和管理由两部分组成，一为病例记录表，二为电子数据采集系统。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Data collection and management consists of two components, case record form (CRF) and an electronic data collection (EDC) system.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-11-14 09:48:53