ChiCTR2400094677 版本V1.0 版本创建时间2024/12/26 08:48:19 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：

 ChiCTR2400094677 

最近更新日期：

Date of Last Refreshed on：

 2024-12-26 08:48:10 

注册时间：

Date of Registration：

 2024-12-26 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

盐酸苯海索片在中国健康人群中空腹和餐后状态下的人体生物等效性临床试验

Public title：

Human bioequivalence of benxoxol hydrochloride tablets in fasting and postprandial state in healthy Chinese population

注册题目简写：

English Acronym：

研究课题的正式科学名称：

盐酸苯海索片在中国健康人群中空腹和餐后状态下单次给药的人体生物等效性临床试验

Scientific title：

Clinical trial of bioequivalence of benxoxol hydrochloride tablets in a single dose of fasting and postprandial state in healthy Chinese population

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：

徐璐薇 

研究负责人：

徐璐薇 

Applicant：

Xu Luwei 

Study leader：

Xu Luwei 

申请注册联系人电话：

Applicant telephone：

 +86 15061003175

研究负责人电话：

Study leader's
telephone：

+86 15061003175

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：

 1511048942@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 283452112@qq.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：

江苏省泰州市海陵区济川东路86号

研究负责人通讯地址：

江苏省泰州市海陵区济川东路86号

Applicant address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

Study leader's address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu 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：

泰州市中医院

Applicant's institution：

Taizhou Hospital of Traditional Chinese Medicine

研究负责人所在单位：

泰州市中医院

Affiliation of the Leader：

Taizhou Hospital of Traditional Chinese Medicine

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：

 2024-050-01

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：

泰州市中医院伦理审查委员会

Name of the ethic committee：

Taizhou Hospital of Traditional Chinese Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-11-11 00:00:00

伦理委员会联系人：

刘影

Contact Name of the ethic committee：

Liu Ying

伦理委员会联系地址：

江苏省泰州市海陵区济川东路86号

Contact Address of the ethic committee：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 523 86611963

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 1511048942@qq.com

研究实施负责（组长）单位：

泰州市中医院

Primary sponsor：

Taizhou Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

江苏省泰州市海陵区济川东路86号

Primary sponsor's address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu 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

市(区县)：

Country：

China

Province：

Jiangsu

City：

单位(医院)：

泰州市中医院

具体地址：

江苏省泰州市海陵区济川东路86号（东院）

Institution
hospital：

Taizhou Hospital of Traditional Chinese Medicine

Address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

经费或物资来源：

北京京丰制药（山东）有限公司

Source(s) of funding：

Beijing Jingfeng Pharmaceutical (Shandong) Co., LTD

研究疾病：

帕金森病  

Target disease：

Parkinsonism

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：

随机交叉对照 

Study design：

Cross-over 

研究目的：

主要目的：以持证商为WATSON LABORATORIES INC的盐酸苯海索片（规格：2mg）为参比制剂，以北京京丰制药（山东）有限公司研发的盐酸苯海索片（规格：2mg）为受试制剂，评价两种制剂在中国健康受试者中空腹和餐后状态下的生物等效性。 次要目的：观察受试制剂和参比制剂在中国健康受试者中的安全性。  

Objectives of Study：

Main Objective: To use benxel hydrochloride tablets (specification: 2mg) from WATSON LABORATORIES INC as the reference preparation, and to use benxel hydrochloride tablets (specification: 2mg) developed by Beijing Jingfeng Pharmaceutical (Shandong) Co., LTD. To evaluate the bioequivalence of the two formulations in fasting and postprandial state in healthy Chinese subjects. Secondary objective: To observe the safety of test preparations and reference preparations in healthy Chinese subjects.

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.受试者了解本试验的目的和要求等，同意遵守试验管理规定，并自愿签署知情同意书； 2.年龄18周岁（含）以上的健康受试者，男女兼有； 3.体重指数（BMI）在[19.0~26.0]之内，包括临界值[BMI=体重/身高2（kg/m^2）]，男性体重>=50.0kg，女性体重>=45.0kg； 4.受试者（或其伴侣）自签署知情同意书前2周至试验用药品最后一次给药后3个月内无生育计划（包括捐精、捐卵）且自愿采取有效避孕措施。

Inclusion criteria

1. The subject understands the purpose and requirements of the trial, agrees to abide by the trial management regulations, and voluntarily signs the informed consent form; 2. Healthy subjects aged 18 years old (inclusive) or above, both male and female; 3. Body mass index (BMI) within [19.0~26.0], including the cut-off value [BMI=weight/height2(kg/m^2)], male weight >=50.0kg, female weight>=45.0kg; 4. The subject (or his partner) has no fertility plan (including sperm donation and egg donation) and voluntarily takes effective contraceptive measures from 2 weeks before signing the informed consent form to 3 months after the last dose of the investigational drug.

排除标准：

1.有神经系统、精神系统、心脑血管系统、内分泌系统、消化系统、泌尿系统、生殖系统、免疫系统、呼吸系统等重要疾病史（包括但不限于有青光眼、前列腺肥大、尿潴留、动脉硬化、迟发性运动障碍、精神异常）且可能影响研究结果评估者；
2.有任何影响药物吸收的胃肠道疾病病史（如肠易激综合征、肠病或炎症性肠病史）、任何影响药物吸收的胆系疾病病史（如急慢性胆囊炎、胆管炎、胆结石、胆汁淤积等）、或接受过胃或小肠切除术、胆囊切除术等任何可能会影响药物吸收的外科手术史，或有萎缩性胃炎、胰腺炎、食管反流、胃肠道出血、消化性溃疡、梗阻等病史者；
3.签署知情同意书前7天内有呕吐、腹泻病史或能干扰试验结果的任何生理状况者；
4.过敏体质，临床上有食物、药物等过敏史，尤其对本试验用药品中任何成分过敏者；
5.签署知情同意书前1年内进行过重大外科手术，或计划在试验期间进行手术者；
6.签署知情同意书前14天内使用过处方药（含疫苗接种）、非处方药、中草药或保健品；
7.签署知情同意书前28天内使用过任何抑制或诱导肝脏药物代谢酶的药物（如：诱导剂--利福平、依非韦仑、巴比妥类、卡马西平、苯妥英、糖皮质激素；抑制剂--SSRI类抗抑郁药、奥美拉唑、西咪替丁、地尔硫卓、大环内酯类、硝基咪唑类、镇静催眠药、氟喹诺酮类、抗组胺类、伊曲康唑、氟康唑）者；
8.签署知情同意书前28天内使用过或试验期间不能放弃使用任何可能与本试验用药品有相互作用的药物，如：中枢神经系统抑制剂、金刚烷胺、抗胆碱药、单胺氧化酶抑制剂、制酸药、吸附性止泻剂、强心苷类药物等；
9.签署知情同意书前3个月内参加过任何药物或医疗器械临床试验者；
10.签署知情同意书前3个月内因献血或其他原因导致失血总和≥400ml者（女性生理性失血除外），或计划在试验期间或试验结束后3个月内捐献血液成分者；
11.服用试验用药前7天内服用过特殊饮食（比如葡萄柚或葡萄柚产品、柚子、火龙果等），不能保证自服药前48小时至试验结束禁食富含黄嘌呤、含咖啡因或酒精的饮料或食物（如：动物内脏、咖啡、浓茶、巧克力、可乐等）者；
12.签署知情同意书前3个月内每天饮用过量茶、咖啡和/或含咖啡因的饮料（8杯以上，1杯=250ml）者；
13.有晕针或晕血史者，或不能耐受静脉穿刺采血者，或采血困难者；
14.对饮食有特殊要求，不能遵守统一饮食安排者或有吞咽困难者；
15.乳糖不耐受者（如：曾发生过喝牛奶腹泻者）；
16.签署知情同意书前3个月内每日吸烟超过5支者或在整个试验期间不能放弃使用烟草产品者；
17.签署知情同意书前6个月内酒精摄入量平均每周超过14单位酒精（1单位≈360ml啤酒/45ml高度白酒/150ml葡萄酒），或试验期间不能放弃饮酒者，或酒精呼气测试>0mg/100ml者；
18.女性受试者筛选时为哺乳期，或妊娠检查结果经研究者判断异常且有临床意义者；
19.有吸毒史或药物滥用史，或尿液药物筛查结果阳性者；
20.乙肝两对半或梅毒螺旋体特异性抗体、艾滋病抗体、丙型肝炎抗体检查结果异常且有临床意义者；
21.体格检查、生命体征检查、12-导联心电图检查、实验室检查结果经研究者判断异常且有临床意义者；
22.在试验前筛选阶段发生急性疾病者；
23.由于其它原因，研究者认为不适合入选者。

Exclusion criteria：

1.Patients with a history of major diseases of the nervous system, mental system, cardiovascular system, endocrine system, digestive system, urinary system, reproductive system, immune system, respiratory system (including but not limited to glaucoma, hypertrophy of the prostate, urinary retention, arteriosclerosis, tartaric dyskinesia, mental disorders) that may affect the evaluation of the study results;
2.Have any history of gastrointestinal disease (such as irritable bowel syndrome, bowel disease or inflammatory bowel disease), any history of biliary disease (such as acute or chronic cholecystitis, cholangitis, gallstones, cholestasis, etc.), or any surgical history of gastric or small intestinal resection, cholecystectomy, etc., that may affect drug absorption, Or have a history of atrophic gastritis, pancreatitis, esophageal reflux, gastrointestinal bleeding, peptic ulcer, obstruction, etc.;
3.The patient has a history of vomiting, diarrhea or any physiological condition that can interfere with the test results within 7 days before signing the informed consent;
4.Allergic constitution, clinical history of food, drug and other allergies, especially allergic to any component of the drug used in the test;
5.Had a major surgical procedure within 1 year prior to signing the informed consent, or planned to have surgery during the trial period;
6.Use of prescription drugs (including vaccines), non-prescription drugs, Chinese herbs or health products within 14 days before signing the informed consent;
7.Use of any drug that inhibits or induces liver drug metabolism enzymes (e.g., inducers - rifampicin, efavir, barbiturates, carbamazepine, phenytoin, glucocorticoids) within 28 days before signing the informed consent; Inhibitors: SSRI antidepressants, omeprazole, cimetidine, Diltiazem, macrolides, nitroimidazoles, sedatives and hypnotics, fluoroquinolones, antihistamines, itraconazole, fluconazole);
8.Any drugs that may interact with the drugs used in the study, such as central nervous system inhibitors, amantadine, anticholinergics, monoamine oxidase inhibitors, acid drugs, adsorbent antidiarrheal agents, cardiac glycosides, etc. that have been used within 28 days before signing the informed consent or during the study period shall not be given up;
9.Have participated in any drug or medical device clinical trial within 3 months before signing the informed consent;
10.Patients with total blood loss ≥400ml due to blood donation or other reasons within 3 months before signing the informed consent (except for female physiological blood loss), or who plan to donate blood components during the trial or within 3 months after the trial;
11.People who have taken a special diet (such as grapefruit or grapefruit products, pomelo, dragon fruit, etc.) in the 7 days prior to the administration of the experimental drug and cannot guarantee the abstinent of xanthine-rich, caffeinated or alcoholic beverages or foods (such as animal offal, coffee, strong tea, chocolate, cola, etc.) from 48 hours prior to the administration until the end of the trial;
12.Excessive consumption of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250ml) per day within 3 months prior to signing the informed consent;
13.Patients who have a history of needle fainting or blood fainting, or who cannot tolerate venous puncture blood collection, or who have difficulty collecting blood;
14.People who have special requirements for diet and cannot comply with a unified diet schedule or have difficulty swallowing;
15.People who are lactose intolerant (such as those who have had diarrhea from drinking milk);
16.Smokers who smoked more than 5 cigarettes per day in the 3 months prior to signing the informed consent or who could not give up the use of tobacco products during the whole test period;
17.Those who consumed more than 14 units of alcohol per week (1 unit ≈360ml beer /45ml high spirits /150ml wine) in the six months before signing the informed consent, or who could not give up drinking during the trial, or whose alcohol breath test was >0mg/100ml;
18.The female subjects were lactating at the time of screening, or the pregnancy test results were abnormal and clinically significant according to the investigators;
19.Have a history of drug use or drug abuse, or positive urine drug screening results;
20.Hepatitis B two-and-a-half or treponema pallidum specific antibody, AIDS antibody, hepatitis C antibody test results abnormal and clinical significance;
21.Physical examination, vital signs examination, 12-lead electrocardiogram examination, laboratory examination results judged by the investigator to be abnormal and clinically significant;
22.Acute disease occurred during the pre-trial screening phase;
23.For other reasons, the researchers did not consider the candidates suitable.

研究实施时间：

Study execute time：

从 From 2024-12-31 00:00:00至 To 2025-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-12-31 00:00:00 至 To 2025-06-01 00:00:00

干预措施：

Interventions：

组别：

餐后组

样本量：

 46

Group：

Postprandial group

Sample size：

干预措施：

两周期餐后交叉服用盐酸苯海索片受试制剂或参比制剂

干预措施代码：

Intervention：

The test preparation or reference preparation of benzoxol hydrochloride tablets should be taken cross-over after two cycles of meals

Intervention code：

组别：

空腹组

样本量：

 46

Group：

Fasting group

Sample size：

干预措施：

两周期空腹交叉服用盐酸苯海索片受试制剂或参比制剂

干预措施代码：

Intervention：

Two cycles of fasting cross administration of benxoxol hydrochloride tablet test preparation or reference preparation

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏 

市(区县)：

  

Country：

China

Province：

Jiangsu

City：

单位(医院)：

 泰州市中医院 

单位级别：

 三甲 

Institution
hospital：

Taizhou Hospital of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

残留面积百分比

指标类型：

主要指标

Outcome：

Percentage of residual area

Type：

Primary indicator

测量时间点：

第一、二周期采血结束后

测量方法：

实验室检查

Measure time point of outcome：

After the first and second cycles of blood collection

Measure method：

Laboratory examination

指标中文名：

生命体征（血压（坐位）、体温（耳温）和脉搏）

指标类型：

次要指标

Outcome：

Vital signs (blood pressure (sitting), body temperature (ear temperature) and pulse)

Type：

Secondary indicator

测量时间点：

每周期给药前1h内、给药后2h、6h、12h、24h、48h、72h、96h、120h

测量方法：

仪器测量

Measure time point of outcome：

Within 1h before administration, 2h, 6h, 12h, 24h, 48h, 72h, 96h, 120h after administration for each

Measure method：

Instrumental measurement

指标中文名：

体格检查

指标类型：

次要指标

Outcome：

Physical examination

Type：

Secondary indicator

测量时间点：

筛选期和第二周期出组前

测量方法：

实验室检查

Measure time point of outcome：

Screening period and before the second cycle out of the group

Measure method：

Laboratory examination

指标中文名：

实验室检查（血常规、血生化、凝血检查、尿常规）

指标类型：

次要指标

Outcome：

Laboratory tests (blood routine, blood biochemistry, coagulation test, urine routine)

Type：

Secondary indicator

测量时间点：

筛选期和第二周期出组前

测量方法：

实验室检查

Measure time point of outcome：

Screening period and before the second cycle out of the group

Measure method：

Laboratory examination

指标中文名：

峰浓度、AUC0-t、AUC0-∞、达峰浓度的时间、消除终末端半衰期、消除速率常数

指标类型：

主要指标

Outcome：

Peak concentration, AUC0-T, AUC0-∞, time to peak concentration, elimination terminal half-life, elimination rate constant

Type：

Primary indicator

测量时间点：

第一、二周期采血结束后

测量方法：

实验室检查

Measure time point of outcome：

After the first and second cycles of blood collection

Measure method：

Laboratory examination

指标中文名：

相对生物利用度

指标类型：

主要指标

Outcome：

Relative bioavailability

Type：

Primary indicator

测量时间点：

第一、二周期采血结束后

测量方法：

实验室检查

Measure time point of outcome：

After the first and second cycles of blood collection

Measure method：

Laboratory examination

指标中文名：

机体总清除率

指标类型：

主要指标

Outcome：

Total body clearance

Type：

Primary indicator

测量时间点：

第一、二周期采血结束后

测量方法：

实验室检查

Measure time point of outcome：

After the first and second cycles of blood collection

Measure method：

Laboratory examination

指标中文名：

表观分布容积

指标类型：

主要指标

Outcome：

Apparent volume of distribution

Type：

Primary indicator

测量时间点：

第一、二周期采血结束后

测量方法：

实验室检查

Measure time point of outcome：

After the first and second cycles of blood collection

Measure method：

Laboratory examination

指标中文名：

12-导联心电图

指标类型：

次要指标

Outcome：

12-lead ECG

Type：

Secondary indicator

测量时间点：

筛选期和第二周期出组前

测量方法：

实验室检查

Measure time point of outcome：

Screening period and before the second cycle out of the group

Measure method：

Laboratory examination

指标中文名：

血妊娠检查（仅育龄女性进行）

指标类型：

次要指标

Outcome：

Blood pregnancy test (only for women of childbearing age)

Type：

Secondary indicator

测量时间点：

筛选期和第二周期出组前

测量方法：

实验室检查

Measure time point of outcome：

Screening period and before the second cycle out of the group

Measure method：

Laboratory examination

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

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：

标本中文名：

尿液

组织：

Sample Name：

Urine

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 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）：

申办方采用SAS 9.4（或更高版本）产生随机表，按1：1的比例使用区组随机方法。该随机数据具有重现性，所设定的随机数初值种子参数需要保存。每名筛选合格的受试者将按照筛选号从小到大的顺序获得随机号（如F001-F046，F代表空腹；A001-A046，A代表餐后）。受试者根据预先制定的随机表随机分配进入TR或RT序列组，并按照相应的给药序列接受相应的试验用药品。

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

Sponsors generate random tables using SAS 9.4 (or later), using the block randomization method on a 1:1 scale. The random data is reproducible, and the seed parameters of the initial value of the random number set need to be saved. Each eligible subject will receive a random number in descending order of screening number (e.g. F001-F046, F stands for fasting; A001-A046, A stands for after dinner). Subjects were randomly assigned to the TR or RT sequence group according to a pre-determined randomization table and received the corresponding investigational drug according to the corresponding dosing sequence.

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：

开放标签，对评估者隐藏分组

Blinding：

Open-label study with blinded-evaluators

是否共享原始数据：

IPD sharing

否No

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）：

无

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

None

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：数据管理员根据试验方案建立eCRF，定义试验流程、数据表单名称及其收集的数据项，同时形成相应的eCRF填写指南，指导研究者及临床协调员（CRC）按照GCP和试验方案要求来收集受试者数据。 数据管理：所有受试者完成试验，数据全部录入系统，由主要研究者、申办者、CRO人员、统计分析人员和数据管理人员召开数据审核会并确认建立的数据库正确后，由数据管理员对数据进行锁定。数据全部锁定后，由数据管理员将其数据集移交统计人员进行统计分析。

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

Data collection: The data manager establishes the eCRF according to the trial protocol, defines the trial procedure, data form name, and data items to be collected, and develops the corresponding eCRF filling guidelines to guide the investigator and clinical coordinator (CRC) to collect subject data according to the GCP and trial protocol requirements. Data management: All subjects complete the test and all data are entered into the system. After the data review meeting is held by the main researcher, sponsor, CRO personnel, statistical analysts and data management personnel and the established database is confirmed to be correct, the data is locked by the data manager. Once all the data is locked, the data manager hands over his or her dataset to the statisticians for statistical analysis.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-12-26 08:48:10