中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400094024
最近更新日期： Date of Last Refreshed on：	2024-12-16 14:56:26
注册时间： Date of Registration：	2024-12-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	单中心、非随机、开放、单序列设计，评估盐酸凯普拉生片和咪达唑仑在中国健康成人中的药物相互作用
Public title：	Evaluation of drug-drug interaction between keverprazan hydrochloride tablets and midazolam in healthy Chinese adults: a single-center, nonrandomized, open-label, single-sequence design clinical trial
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、单序列设计，评估盐酸凯普拉生片和咪达唑仑在中国健康成人中的药物相互作用
Scientific title：	Evaluation of drug-drug interaction between keverprazan hydrochloride tablets and midazolam in healthy Chinese adults: a single-center, nonrandomized, open-label, single-sequence 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：	杨水新
Applicant：	Yaqiong Jiang	Study leader：	Shuixin Yang
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：	+86 138 1923 3850
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：	phase1@163.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：	浙江省湖州市三环北路1558号
Applicant address：	6 Xuzhuang Road, Xuanwu District, Nanjing, Jiangsu, China	Study leader's address：	1558 North Third Ring Road, Huzhou City, Zhejiang Province
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：	湖州市中心医院
Affiliation of the Leader：	Huzhou Central 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：	2024-059(Y)-01	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：	湖州市中心医院临床试验伦理委员会
Name of the ethic committee：	Huzhou Central Hospital Clinical Trial Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2024-10-11 00:00:00
伦理委员会联系人：	蒋凤琴
Contact Name of the ethic committee：	Fengqin Jiang
伦理委员会联系地址：	浙江省湖州市三环北路1558号
Contact Address of the ethic committee：	1558 North Third Ring Road, Huzhou City, Zhejiang Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 572 270 9719	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：

湖州市中心医院

Primary sponsor：

Huzhou Central Hospital

研究实施负责（组长）单位地址：

浙江省湖州市三环北路1558号

Primary sponsor's address：

1558 North Third Ring Road, Huzhou City, Zhejiang Province

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
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：	江苏省南京市玄武区徐庄路6号
Institution hospital：	Jiangsu Carephar Pharmaceutical Co., Ltd	Address：	6 Xuzhuang Road, Xuanwu District, Nanjing, Jiangsu

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：

其它

Study phase：

N/A

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：考察盐酸凯普拉生片和咪达唑仑联合使用时相对于咪达唑仑单独使用时，对咪达唑仑药代动力学的影响。次要目的：考察盐酸凯普拉生片与咪达唑仑联合使用的安全性和耐受性。

Objectives of Study：

Primary Objective: To assess the effect of drug combination of keplasen hydrochloride tablets and midazolam, as well as midazolam used alone, on the pharmacokinetics of midazolam. Secondary Objective: To assess the safety and tolerability of the drug combination of keplasen hydrochloride tablets and midazolam.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. subjects fully understand the purpose, content, process and possible adverse effects of the trial, volunteer to be subjects, and sign the informed consent form prior to the commencement of any trial procedure;
2. healthy men or women aged 18-45 years (including 18 years and 45 years) (healthy means that the results of all tests related to the trial, such as past history questioning, physical examination, vital signs, laboratory tests (blood, urine, blood biochemistry and coagulation function tests) and 12-lead electrocardiogram, are normal or abnormal but not clinically significant in the judgment of the investigator);
3. weight >=50.0kg for men and >=45.0kg for women; body mass index (BMI) within the range of 19~26kg/m2 (including the critical value), BMI=weight (kg)/height2 (m2);
4. subjects (including partners) 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 3 months after the last administration of the test drug;
5. subjects are able to communicate well with the investigator and understand and comply with the requirements of the trial.

排除标准：

1. 对凯普拉生、咪达唑仑、或任意试验用药品组分有过敏史，或已知过敏原，或有特异性变态反应性疾病史、药物过敏史； 2. 有长QT综合征家族史（祖父母、父母和兄弟姐妹）； 3. 有神经系统、心血管系统、血液和淋巴系统、免疫系统、肾脏、肝脏、胃肠道、呼吸系统、代谢及骨骼等系统疾病、感染性疾病、重要脏器疾病史且经研究者判断不宜参加试验； 4. 有可能显著影响药物吸收、分布、代谢和排泄的任何疾病或病史，或者可能对受试者构成危害的任何病情，如： i. 炎症性肠病、胃溃疡、十二指肠溃疡、胃肠道/直肠出血、持久性恶心或其他具有临床意义的胃肠道异常； ii. 既往有较大的胃肠道手术史（比如：胃切除术、胃肠吻合术、肠切除术、胃旁路术、胃分割述或胃囊带术、胆囊切除术，但阑尾炎手术和脱肛术除外）； iii. 筛选时有肝病或具有肝功能不全的病史或证据（如AST、ALT或总胆红素＞1.5倍ULN）； iv. 筛选时有肾病或具有肾功能不全的病史或证据，表现为有临床意义的肌酐异常或尿成分异常（比如蛋白尿等）； v. 筛选期尿路梗阻或尿排空困难； 5. 不能耐受静脉穿刺；或有晕针晕血史； 6. 女性参与者筛选前30天内使用口服避孕药；或筛选前6个月内使用长效雌激素或孕激素注射剂或埋植片； 7. 女性参与者正处在哺乳期或妊娠期；或血妊娠检查呈阳性； 8. 筛选前3年内有药物滥用史或使用过毒品；或尿药物滥用筛查结果阳性； 9. 筛选前3个月内接受过重大手术，或计划在试验期间进行手术； 10. 筛选前3个月内献血（包括成分血）或大量失血（≥400mL，女性生理性失血除外），或接受输血或使用血制品； 11. 筛选前3个月内平均每日吸烟量多于5支；或试验期间不能停止使用任何烟草类产品； 12. 筛选前3个月内每天饮用过量茶、咖啡和富含咖啡因的饮料（8杯以上，1杯=250 mL）； 13. 筛选前3个月内平均每周饮酒量大于14个单位（1单位酒精约含18毫升酒精≈355 mL啤酒或45 mL酒精含量为40%的烈酒或150 mL葡萄酒）；或试验期间不能禁酒；或酒精呼气试验结果阳性； 14. 筛选前3个月内使用过试验用药品，或参加过其他临床试验； 15. 筛选前1个月内接种过疫苗，或试验结束后1个月内计划接种疫苗； 16. 筛选前28天内使用过任何改变肝酶活性的药物，或使用过任何CYP3A4抑制剂或诱导剂（CYP3A4抑制剂和诱导剂详见附录2）； 17. 筛选前14天内使用过任何处方药、非处方药、中草药或维生素等保健品； 18. 筛选前14天内摄取过量特殊饮食；或给予试验用药品前48h摄取任何特殊饮食；或试验期间不能停止摄取特殊饮食（特殊饮食指：火龙果、芒果、葡萄柚、富含黄嘌呤类以及含咖啡因、酒精等可能影响药物吸收、分布、代谢、排泄的食物和/或饮料）； 19. 自签署知情同意书至给予试验用药品前发生急性疾病或有合并用药； 20. 自签署知情同意书至试验结束期间不能禁止剧烈运动或其他任何可能严重影响药物吸收、分布、代谢和排泄的各种情况； 21. 对饮食有特殊要求，不能接受统一饮食，或有吞咽困难者； 22. 术前四项检查，即乙型肝炎病毒表面抗原（HBsAg）、丙型肝炎病毒抗体（HCV-Ab）、人类免疫缺陷病毒HIV（1+2）抗体+p24抗原、梅毒特异性抗体，检查有临床意义者； 23. 研究者认为有不适合参加本试验的其他因素。

Exclusion criteria：

1. subjects with a history of allergy to keplasen, midazolam, or any of the test drug components, or known allergens, or a history of atopic anaphylactic diseases, or drug allergy; 2. subjects have a family history of long QT syndrome (grandparents, parents, and siblings); 3. subjects have a history of neurological, cardiovascular, hematologic and lymphatic, immune, renal, hepatic, gastrointestinal, respiratory, metabolic, and skeletal or other systemic diseases, infectious diseases, or diseases of the vital organs that, in the judgment of the investigator, make participation in the trial inappropriate 4. subjects have any disease or history of disease that may significantly affect the absorption, distribution, metabolism and excretion of the drug, or have any condition that may pose a hazard to subjects, such as: (1) subjects have inflammatory bowel disease, gastric ulcers, duodenal ulcers, gastrointestinal/rectal bleeding, persistent nausea, or other clinically significant gastrointestinal abnormalities; (2) subjects have a prior history of major gastrointestinal surgery (e.g., gastrectomy, gastrointestinal anastomosis, bowel resection, gastric bypass, gastric division of said or gastric pouch banding, cholecystectomy, with the exception of appendicitis surgery and prolapse); (3) subjects with liver disease or a history or evidence of hepatic insufficiency (e.g., AST, ALT, or total bilirubin > 1.5 times ULN) at screening; (4) subject have renal disease or a history or evidence of renal insufficiency at screening as evidenced by clinically significant creatinine abnormalities or abnormal urine composition (e.g., proteinuria, etc.); (5) urinary obstruction or difficult urinary emptying during screening 5. subjects are unable to tolerate venipuncture; or have a history of needle and blood-sickness; 6. female participants have used oral contraceptives within 30 days prior to screening; or have used long-acting estrogen or progestin injections or buried tablets within 6 months prior to screening; 7. female participants are breastfeeding or pregnant; or have a positive blood pregnancy test; 8. subjects have a history of substance abuse or drug use within 3 years prior to screening; or have a positive urine substance abuse screen; 9. subjects have undergone a major surgical procedure within 3 months prior to screening, or are scheduled to undergo a procedure during the trial; 10. subjects have donated blood (including component blood) or lost a significant amount of blood (>=400mL, except for physiologic blood loss in females), or received a blood transfusion or used blood products within 3 months prior to screening 11. subjects have smoked an average of more than 5 cigarettes per day in the 3 months prior to screening; or are unable to stop using any tobacco products during the trial; 12. subjects have consumed excessive amounts of tea, coffee, and caffeine-rich beverages (more than 8 cups, 1 cup = 250 mL) per day during the 3 months prior to screening; 13. subjects have consumed an average of greater than 14 units of alcohol per week (1 unit of alcohol contains approximately 18 milliliters of alcohol ≈ 355 mL of beer or 45 mL of 40% alcohol by volume or 150 mL of wine) in the 3 months prior to screening; or are unable to discontinue alcohol consumption during the test period; or have a positive breath test result for alcohol; 14. subjects have used a test drug or participated in another clinical trial within 3 months prior to screening; 15. subjects have been vaccinated within 1 month prior to screening, or are scheduled to be vaccinated within 1 month of the end of the trial; 16. subjects have used any drug that alters hepatic enzyme activity or have used any CYP3A4 inhibitor or inducer within 28 days prior to screening; 17. subjects have used any prescription, over-the-counter, herbal or vitamin supplements within 14 days prior to screening; 18. subjects have consumed a special diet within 14 days prior to screening; or have consumed any special diet 48 hours prior to administration of the test drug; or are unable to stop consuming a special diet during the trial (special diets refer to: dragon fruit, mango, grapefruit, xanthine-rich, caffeine-containing, alcohol-containing, and other foods and/or beverages that may interfere with the absorption, distribution, metabolism, or excretion of the drug); 19. acute illness or coadministration of medication from the time of signing the informed consent to the time of administration of the test drug; 20. subjects are unable to stop strenuous exercise or any other conditions that may seriously affect the absorption, distribution, metabolism and excretion of the drug during the period from the signing of the informed consent to the end of the trial; 21. subjects have special dietary requirements, cannot accept a uniform diet, or have difficulty swallowing; 22. subjects with clinically significant preoperative four tests, i.e. Hepatitis B virus surface antigen (HBsAg), Hepatitis C virus antibody (HCV-Ab), Human Immunodeficiency Virus HIV (1+2) Antibody + p24 Antigen, and Syphilis Specific Antibody tests; 23. other factors considered by the investigator to be inappropriate for participation in this trial.

研究实施时间：

Study execute time：

从 From 2024-12-23 00:00:00至 To 2025-06-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-12-24 00:00:00 至 To 2025-06-15 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	20
Group：	Experimental group	Sample size：	20
干预措施：	试验第1天单次空腹口服15mg马来酸咪达唑仑片，试验第3天至第8天每天单次空腹口服20mg盐酸凯普拉生片，试验第9天单次空腹口服15mg马来酸咪达唑仑片和20mg盐酸凯普拉生片。	干预措施代码：
Intervention：	A single fasting oral dose of 15 mg midazolam maleate tablets was administered on day 1 of the trial, a single fasting oral dose of 20 mg keplasen hydrochloride tablets was administered daily on days 3 through 8 of the trial, and a single fasting oral dose of 15 mg midazolam maleate tablets and 20 mg keplasen hydrochloride tablets was administered on day 9 of the trial.	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	浙江省	市(区县)：	湖州
Country：	China	Province：	Zhejiang	City：	Huzhou
单位(医院)：	湖州市中心医院	单位级别：	三甲
Institution hospital：	Huzhou Central 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	45	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）：	国家药品监督管理局药品审评中心：https://www.cde.org.cn/，在试验结束6个月内上传试验数据
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Center for Drug Evaluation, National Medical Products Administration: https://www.cde.org.cn/, to upload trial data within 6 months after the end of the trial
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：	2024-12-16 14:56:19