ChiCTR2400083953 版本V1.0 版本创建时间2024/05/08 10:46:32 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：

ChiCTR2400083953 

最近更新日期：

Date of Last Refreshed on：

2024-05-08 10:46:27 

注册时间：

Date of Registration：

2024-05-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

富马酸伏诺拉生片（20 mg）人体生物等效性研究

Public title：

Study on the bioequivalence of Fumarate Vonorasone Tablets (20 mg) in humans

注册题目简写：

English Acronym：

研究课题的正式科学名称：

富马酸伏诺拉生片（20 mg）人体生物等效性研究

Scientific title：

Study on the bioequivalence of Fumarate Vonorasone Tablets (20 mg) in humans

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：

王炜玮 

研究负责人：

杨水新 

Applicant：

Wang Weiwei  

Study leader：

Yang Shuixin 

申请注册联系人电话：

Applicant telephone：

+86 183 0508 0962

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：

wangweiweis@qq.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：

浙江省湖州市吴兴区三环北路1558号

研究负责人通讯地址：

浙江省湖州市吴兴区三环北路1558号

Applicant address：

1558 Sanhuan North Road, Wuxing District, Huzhou City, Zhejiang Province

Study leader's address：

1558 Sanhuan North Road, Wuxing District, 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：

湖州市中心医院

Applicant's institution：

Huzhou Central Hospital

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/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

2024-022(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：

Clinical Trial Ethics Committee of Huzhou Central Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2024-04-16 00:00:00

伦理委员会联系人：

蒋凤琴

Contact Name of the ethic committee：

Jiang Fengqin

伦理委员会联系地址：

浙江省湖州市吴兴区三环北路1558号

Contact Address of the ethic committee：

1558 Sanhuan North Road, Wuxing District, 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：

浙江省湖州市吴兴区三环北路1558号

Primary sponsor's address：

1558 Sanhuan North Road, Wuxing District, 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)：

浙江

市(区县)：

Country：

China

Province：

Zhejiang

City：

单位(医院)：

浙江尖峰药业有限公司

具体地址：

浙江省金华市婺城区白汤下线高畈段58号X02幢办公质检楼二楼

Institution
hospital：

Jiang Feng Pharmaceutical

Address：

Building X02, 2nd Floor, Office Quality Inspection Building, No. 58 Gaofan Section, Baitangxia Line, Wucheng District, Jinhua City, Zhejiang Province

经费或物资来源：

浙江尖峰药业有限公司

Source(s) of funding：

Jiang Feng Pharmaceutical

Target disease：

Reflux esophagitis

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期临床试验 

Study phase：

1

研究设计：

随机交叉对照 

Study design：

Cross-over 

研究目的：

以浙江尖峰药业有限公司研制的富马酸伏诺拉生片（规格：20 mg）为受试制剂，生产商为Takeda Pharmaceutical Company Limited的富马酸伏诺拉生片（商品名：沃克?/Vocinti?，规格：20 mg）为参比制剂，考察两制剂在空腹及餐后状态下单次给药的药代动力学参数及相对生物利用度，评价两制剂是否具有生物等效性。同时评价两制剂在健康人体中的安全性和耐受性。  

Objectives of Study：

Fumarate Vonorasone Tablets (specification: 20 mg) developed by Zhejiang Jianfeng Pharmaceutical Co., Ltd. were used as the test formulation, manufactured by Takeda Pharmaceutical Company Limited (trade name: Walker) ?/ Vocinti ?, Specification: 20 mg) is a reference formulation, and the pharmacokinetic parameters and relative bioavailability of the two formulations administered in a single dose on an empty stomach and after meals are evaluated to determine their bioequivalence. Simultaneously evaluate the safety and tolerability of the two formulations in healthy individuals.

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. 性别：健康男性或女性受试者； 2. 年龄：18周岁以上（包括18周岁； 3. 体重：男性受试者不应低于50.0 kg，女性受试者不应低于45.0 kg，身体质量指数[BMI=体重(kg)/身高2(m2)]在19.0～26.0 kg/m2范围内（包括边界值）； 4. 自愿参加并签署知情同意书者；获得知情同意书过程符合GCP； 5. 受试者能够和研究者进行良好的沟通，并且理解和遵守本项研究的各项要求者。

Inclusion criteria

1. Gender: Healthy male or female subjects; 2. Age: 18 years old and above (including 18 years old); 3. Weight: Male subjects should not be less than 50.0 kg, female subjects should not be less than 45.0 kg, and the body mass index [BMI=weight (kg)/height 2 (m2)] should be within the range of 19.0 to 26.0 kg/m2 (including boundary values); 4. Those who voluntarily participate and sign an informed consent form; The process of obtaining informed consent forms complies with GCP; 5. The subjects are able to communicate well with the researchers and understand and comply with the requirements of this study.

排除标准：

1. 生命体征、体格检查、血常规、血生化、凝血检查、尿常规、12导联心电图、女性血妊娠、术前四项检查中有异常且经研究者判定具有临床意义者；? 2. 有肝、肾、消化道、内分泌系统、心脑血管系统、神经系统、代谢系统、血液和淋巴系统、眼（如青光眼）、胃肠道系统（如幽门十二指肠梗阻）、呼吸系统及自身免疫系统等慢性疾病或严重疾病史或现有上述系统疾病者，且由研究者判定不适合入组者；? 3. 近6个月内受试者有胃酸相关性疾病（如：有症状性胃食管反流病、糜烂性食管炎、胃溃疡、十二指肠溃疡、消化不良等）者；? 4. 有精神疾病史、药物滥用史、药物依赖史者；? 5. 对饮食有特殊要求，不能遵守统一饮食者；或有吞咽困难者；? 6. 对其它药物、食物、环境过敏累计两项或以上者；或既往对伏诺拉生及辅料中任何成分过敏者；? 7. 筛选前30天内使用过任何与伏诺拉生存在相互作用的药物（如CYP3A4或P-gp抑制剂酮康唑、伊曲康唑、克拉霉素、红霉素、氟康唑、阿扎那韦、印地那韦、萘法唑酮、那非那韦、利托那韦、沙奎那韦、泰利霉素、伏立康唑等；CYP3A4诱导剂地塞米松、苯妥英、卡马西平、利福平、利福布汀、利福喷汀、苯巴比妥、圣约翰草等）者；或筛选前14天内使用过任何处方药、非处方药、中草药、保健品者；? 8. 筛选前3个月内饮用过量（一天8杯以上，1杯=250 mL）茶、咖啡或含咖啡因的饮料者；或给药前48 h内，服用茶或任何含有咖啡因的食物或饮料（如咖啡、巧克力等）者；? 9. 筛选前14天内摄入大量富含葡萄柚（西柚）的饮料或食物者（如葡萄柚、葡萄柚汁、葡萄柚果酱等）；或给药前48 h内，摄入过任何富含葡萄柚（西柚）的饮料或食物者；? 10. 采血困难或不能耐受静脉留置针采血者；有晕针、晕血史者；? 11. 筛选前3个月内平均每周饮酒超过14个标准单位（1标准单位含14 g酒精，如360 mL啤酒或45 mL酒精量为40%的烈酒或150 mL葡萄酒）者；或不同意自筛选日至试验结束期间禁酒者；? 12. 筛选前3个月平均每日吸烟量≥5支者，或不同意自筛选日至试验结束期间禁烟者；? 13. 筛选前3个月内参加过其它临床试验者；? 14. 筛选前3个月内有过献血史者或大量出血（>400 mL）（女性生理期除外），或计划在试验期间或试验后献血者；? 15. 筛选前3个月或筛选期间内接受过手术，或接受过影响药物吸收、分布、代谢、排泄的手术，或计划在研究期间进行手术者；? 16. 入住当天药物滥用筛查（吗啡、四氢大麻酚酸、甲基安非他明、二亚甲基双氧安非他明、氯胺酮）检测阳性者；或入住当天酒精呼气检测结果阳性者；? 17. 筛选前1个月内接种过疫苗，或计划在试验期间接种疫苗者；? 18. 妊娠或哺乳期妇女，女性受试者自筛选前14天至末次给药后3个月内，以及男性受试者（或其伴侣）在整个试验期间及研究结束后3个月内有生育计划，试验期间不愿采取一种或一种以上的非药物避孕措施（如完全禁欲、避孕套等）者；? 19. 遗传性半乳糖不耐受、Lapp乳糖酶缺乏或葡萄糖-半乳糖吸收不良者（曾发生过喝牛奶腹泻）；? 20. 研究者认为因其它原因不适合入组的受试者或受试者因自身原因退出试验者。

Exclusion criteria：

1. Those who have abnormalities in vital signs, physical examination, blood routine, blood biochemistry, coagulation test, urine routine, 12 lead electrocardiogram, female blood pregnancy, and preoperative four tests and have been determined by the researcher to have clinical significance; 2. Individuals with a history of chronic or serious diseases such as liver, kidney, digestive tract, endocrine system, cardiovascular and cerebrovascular system, nervous system, metabolic system, blood and lymphatic system, eye (such as glaucoma), gastrointestinal system (such as pyloric duodenal obstruction), respiratory system, and autoimmune system, or existing diseases of the aforementioned systems, and those deemed unsuitable for enrollment by the researcher; 3. Subjects with gastric acid related diseases (such as symptomatic gastroesophageal reflux disease, erosive esophagitis, gastric ulcers, duodenal ulcers, indigestion, etc.) within the past 6 months; 4. Individuals with a history of mental illness, drug abuse, or drug dependence; 5. Those who have special dietary requirements and cannot follow a unified diet; Or those with swallowing difficulties; 6. Those who have accumulated two or more allergies to other drugs, food, or the environment; Or those who have a history of allergies to any ingredients in voronorgestrel and its excipients; 7. Those who have used any drugs that interact with vorolaxen within the first 30 days of screening (such as CYP3A4 or P-gp inhibitors ketoconazole, itraconazole, clarithromycin, erythromycin, fluconazole, azanavir, indinavir, naphazolone, narfenavir, ritonavir, saquinavir, telithromycin, voriconazole, etc.; CYP3A4 inducers dexamethasone, phenytoin, carbamazepine, rifampicin, rifampicin, rifampicin, rifampicin, phenobarbital, St. John's grass, etc.); Or screen those who have used any prescription drugs, over-the-counter drugs, Chinese herbal medicines, or health products within the past 14 days; 8. Screening for individuals who have consumed excessive amounts (8 or more cups per day, 1 cup=250 mL) of tea, coffee, or caffeinated beverages within the first 3 months; Take tea or any food or beverage containing caffeine (such as coffee, chocolate, etc.) within 48 hours before administration; 9. Screening for individuals who consume a large amount of grapefruit rich beverages or foods within the first 14 days (such as grapefruit, grapefruit juice, grapefruit jam, etc.); Individuals who have consumed any beverage or food rich in grapefruit (grapefruit) within 48 hours prior to administration; 10. Difficulty in blood collection or inability to tolerate venous indwelling needle blood collection; Individuals with a history of fainting needles or blood; 11. Screening for individuals who have consumed an average of more than 14 standard units of alcohol per week within the first three months (1 standard unit containing 14 g of alcohol, such as 360 mL of beer, 45 mL of 40% alcohol or 150 mL of wine); Or those who do not agree to abstain from alcohol during the period from the screening date to the end of the experiment; 12. Those who smoke an average of 5 cigarettes per day or more in the first 3 months of screening, or those who do not agree to a smoking ban from the screening date to the end of the experiment; 13. Screening for individuals who have participated in other clinical trials within the first three months; 14. Screening for individuals with a history of blood donation or significant bleeding (>400 mL) within the first three months (excluding female menstrual periods), or those who plan to donate blood during or after the trial; 15. Those who have undergone surgery within the first 3 months or screening period, or have undergone surgery that affects drug absorption, distribution, metabolism, and excretion, or plan to undergo surgery during the study period; 16. Those who test positive for drug abuse screening (morphine, tetrahydrocannabidiol acid, methamphetamine, dimethylenedioxoamphetamine, ketamine) on the day of check-in; Or those who have a positive alcohol breath test result on the day of check-in; 17. Screening for individuals who have received vaccines within the previous month or plan to receive vaccines during the trial period; 18. Pregnant or lactating women, female subjects from 14 days prior to screening to 3 months after the last dose, and male subjects (or their partners) who have a fertility plan throughout the entire trial period and 3 months after the end of the study, and are unwilling to use one or more non pharmacological contraceptive measures (such as complete abstinence, condoms, etc.) during the trial period; 19. Individuals with hereditary galactose intolerance, Lapp lactase deficiency, or glucose galactose malabsorption (who have experienced diarrhea from drinking milk); 20. Participants who are deemed unsuitable for enrollment due to other reasons by the researchers or who withdraw from the trial due to their own reasons.

研究实施时间：

Study execute time：

从 From 2024-05-15 00:00:00至 To 2024-08-15 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-05-17 00:00:00 至 To 2024-06-08 00:00:00  

干预措施：

Interventions：

组别：

空腹T-R组

样本量：

16

Group：

Fasting T-R Group

Sample size：

干预措施：

受试者在第一周期服用受试制剂，第二周期服用参比制剂。

干预措施代码：

Intervention：

The subjects took the test formulation in the first cycle and the reference formulation in the second cycle.

Intervention code：

组别：

餐后T-R组

样本量：

18

Group：

Postprandial T-R group

Sample size：

干预措施：

餐后状态下，受试者在第一周期服用受试制剂，第二周期服用参比制剂。

干预措施代码：

Intervention：

After meals, the subjects took the test formulation in the first cycle and the reference formulation in the second cycle.

Intervention code：

组别：

空腹R-T组

样本量：

16

Group：

Fasting R-T group

Sample size：

干预措施：

受试者在第一周期服用参比制剂，第二周期服用受试制剂。

干预措施代码：

Intervention：

The subjects took the reference formulation in the first cycle and the test formulation in the second cycle.

Intervention code：

组别：

餐后R-T组

样本量：

18

Group：

Postprandial R-T group

Sample size：

干预措施：

餐后状态下，受试者在第一周期服参比制剂，第二周期服用受试制剂。

干预措施代码：

Intervention：

After meals, the subjects took the reference formulation in the first cycle and the test formulation in the second cycle.

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)：

  

Country：

China 

Province：

Zhejiang 

City：

 

单位(医院)：

湖州市中心医院 

单位级别：

三甲甲等 

Institution
hospital：

Huzhou Central Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

峰浓度

指标类型：

主要指标

Outcome：

Cmax

Type：

Primary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

根据血药浓度-时间实测数据直接获得

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

Directly obtained from the measured data of blood drug concentration time.

指标中文名：

从给药到可最后一个检测最低血药浓度的时间t的曲线下面积

指标类型：

主要指标

Outcome：

AUC0-t

Type：

Primary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

通过线性梯形法则计算

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

Calculate using the linear trapezoidal rule

指标中文名：

从给药到外推至无穷远时间的曲线下面积

指标类型：

主要指标

Outcome：

AUC0-∞

Type：

Primary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

AUC0-∞=AUC0-t+Ct/λz，Ct是最后可测量浓度，λz是消除速率常数

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

AUC0- ∞=AUC0-t+Ct/ λ z. Ct is the final measurable concentration, λ Z is the elimination rate constant

指标中文名：

达峰浓度的时间

指标类型：

次要指标

Outcome：

Tmax

Type：

Secondary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

根据血药浓度-时间实测数据直接获得

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

Directly obtained from measured blood drug concentration time data

指标中文名：

消除速率常数

指标类型：

次要指标

Outcome：

λz

Type：

Secondary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

使用线性回归方法计算的半对数药时曲线终末段的斜率，取斜率的相反数

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

Calculate the slope of the final segment of the semi logarithmic drug time curve using linear regression method, taking the opposite of the slope

指标中文名：

消除终末端半衰期

指标类型：

次要指标

Outcome：

Eliminating terminal half-life

Type：

Secondary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

按照ln2/λz计算

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

According to ln2/ λ Z calculation

指标中文名：

残留面积百分比

指标类型：

主要指标

Outcome：

AUC_%Extrap

Type：

Primary indicator

测量时间点：

空腹19个采血点，餐后20个采血点

测量方法：

以[(AUC0-∞-AUC0-t)/ AUC0-∞]×100%计算

Measure time point of outcome：

19 blood collection points on an empty stomach and 20 blood collection points after meals

Measure method：

Calculated at [(AUC0- ∞ - AUC0 t)/AUC0- ∞] x 100%

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：

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 65 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）：

本研究采用单中心、随机、开放、两制剂、空腹/餐后、单次给药、两周期、双交叉设计。统计分析单位采用 SAS 9.4（或更新版本）按照简单随机抽样方法生成药物随机表。空腹和餐后试验分别随机，受试者随机表由统计单位应用SAS9.4按区组随机方法产生。在筛选时，每名受试者将使用筛选号进行识别，筛选号以四位阿拉伯数字表示（如0001、0002…），随机时，每名合格的受试者将按照筛选号从小到大获得随机号，空腹试验和餐后试验分别随机，K001-K032表示空腹试验受试者随机号，C001-C036表示餐后试验受试者随机号。

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

This study adopted a single center, randomized, open label, two dose, fasting/postprandial, single dose, two cycle, double crossover design. The statistical analysis unit uses SAS 9.4 (or updated version) to generate a drug randomization table using a simple random sampling method. The fasting and postprandial trials were randomized separately, and the subject randomization table was generated by the statistical unit using SAS9.4 block by block randomization method. During screening, each subject will be identified using a screening number, which is represented by four Arabic numerals (such as 0001, 0002...). During randomization, each qualified subject will receive a random number in ascending order based on the screening number. Fasting and postprandial trials will be randomized separately, with K001-K032 representing the fasting trial subject random number and C001-C036 representing the postprandial trial subject random number.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

开放标签

Blinding：

Open tags

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

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）：

NA

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

NA

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：

NA

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

NA

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-05-08 10:46:27