ChiCTR2500097129 版本V1.0 版本创建时间2025/02/13 08:47:51 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：

 ChiCTR2500097129 

最近更新日期：

Date of Last Refreshed on：

 2025-02-13 08:47:33 

注册时间：

Date of Registration：

 2025-02-13 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

中国健康受试者空腹及餐后状态下单次口服艾司唑仑片的单中心、开放、随机、两制剂、两序列、两周期、双交叉人体生物等效性试验

Public title：

A single-center, open-label, randomized, two-formulation, two-sequence, two-cycle, double-cross human bioequivalence trial of single oral administration of estazolam tablets in fasting and postprandial states in Chinese healthy subjects

注册题目简写：

English Acronym：

Human bioequivalence test of estazolam tablets

研究课题的正式科学名称：

中国健康受试者空腹及餐后状态下单次口服艾司唑仑片的单中心、开放、随机、两制剂、两序列、两周期、双交叉人体生物等效性试验

Scientific title：

A single-center, open-label, randomized, two-formulation, two-sequence, two-cycle, double-cross human bioequivalence trial of single oral administration of estazolam tablets in fasting and postprandial states in Chinese healthy subjects

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：

赵永辰 

研究负责人：

赵永辰 

Applicant：

Yongchen Zhao 

Study leader：

Yongchen Zhao 

申请注册联系人电话：

Applicant telephone：

 +86 312 5981186

研究负责人电话：

Study leader's
telephone：

+86 312 5981186

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：

 zhaoyongchen69@163.com

研究负责人电子邮件：

Study leader's E-mail：

 zhaoyongchen69@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：

河北省保定市保定市莲池区东风东路648号河北大学附属医院

研究负责人通讯地址：

河北省保定市裕华东路212号

Applicant address：

Hebei University Affiliated Hospital, Baoding City, Hebei Province

Study leader's address：

212 Yuhua East Road, Baoding City, Hebei 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：

河北大学附属医院

Applicant's institution：

Hebei University Affiliated Hospital

研究负责人所在单位：

河北大学附属医院

Affiliation of the Leader：

Affiliated Hospital of Hebei University

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：

 HDFYLL-GCP-2024-296

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：

河北大学附属医院伦理委员会

Name of the ethic committee：

Ethics Committee of Affiliated Hospital of Hebei University

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-09-14 00:00:00

伦理委员会联系人：

王冰

Contact Name of the ethic committee：

Bing Wang

伦理委员会联系地址：

河北省保定市裕华东路212号

Contact Address of the ethic committee：

212 Yuhua East Road, Baoding City, Hebei Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 312 5981513

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 15128989120@126.com.cn

研究实施负责（组长）单位：

河北大学附属医院

Primary sponsor：

Affiliated Hospital of Hebei University

研究实施负责（组长）单位地址：

河北省保定市裕华东路212号

Primary sponsor's address：

212 Yuhua East Road, Baoding City, Hebei 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)：

河北

市(区县)：

Country：

China

Province：

Hebei

City：

单位(医院)：

河北大学附属医院

具体地址：

河北省保定市裕华东路212号

Institution
hospital：

Affiliated Hospital of Hebei University

Address：

212 Yuhua East Road, Baoding City, Hebei Province

经费或物资来源：

广东南国药业有限公司

Source(s) of funding：

Guangdong Nanguo Pharmaceutical Co., Ltd

研究疾病：

无  

Target disease：

NA

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：

研究健康受试者空腹及餐后单次口服受试制剂艾司唑仑片（广东南国药业有限公司，规格：1mg）与参比制剂艾司唑仑片（商品名：EURODIN?；Teva Takeda Yakuhin Ltd.，规格：1mg）在吸收程度和速度方面是否存在差异，评价受试制剂和参比制剂在空腹及餐后状态下给药时的生物等效性，观察受试制剂和参比制剂在健康受试者中的安全性。  

Objectives of Study：

In the study, healthy subjects were given a single oral administration of the test preparation estazolam tablets (Guangdong Nanguo Pharmaceutical Co., Ltd., specification: 1mg) and the reference preparation estazolam tablets (trade name: EURODIN;? Teva Takeda Yakuhin Ltd., specification: 1 mg), to evaluate the bioequivalence of the test preparation and the reference formulation when administered on an empty stomach and in the postprandial state, and to observe the safety of the test preparation and the reference formulation in healthy 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)性别：健康成年男性和女性受试者，并有适当比例； 2)年龄：18周岁以上（含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，且体重指数BMI[体重（kg）/身高^2（m^2）]在19.0 kg/m^2~26.0kg/m^2范围之内（含边界值）； 4)受试者能够和研究者进行良好的沟通，并且理解和遵守本研究的各项要求； 5)受试者对知情同意书的内容充分理解并自愿签署，自愿参加该试验。

Inclusion criteria

1. Gender: healthy adult male and female subjects with appropriate proportions; 2. Age: 18 years old or 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 body mass index BMI [weight (kg)/height ^2 (m^2)] is within the range of 19.0 kg/m^2~26.0kg/m^2 (including boundary value); 4. The subject can communicate well with the investigator, and understand and comply with the requirements of this study; 5.Subjects fully understand the content of the informed consent form and voluntarily sign it, and voluntarily participate in the trial.

排除标准：

1)筛选期体格检查、生命体征测量、心电图检查、实验室检查包括【血常规、尿常规、血生化、凝血功能检查、妊娠检查（仅限女性受试者）、血清病毒学检查】，研究者判断异常有临床意义者； 2)患有呼吸系统（包括肺心病、肺气肿、支气管哮喘者）、消化系统（特别关注试验前一周有严重腹泻者）、心血管系统、血液和淋巴系统、精神和神经系统（特别关注癫痫病史）、生殖泌尿系统、内分泌系统、肝脏、肾脏以及代谢异常等任何临床严重疾病史（包括给药前1年内患有重大疾病或接受过重大外科手术者）或能干扰试验结果的任何其他疾病史或生理情况者； 3)现患有以下疾病者：重症肌无力、严重慢性阻塞性肺部病变、急性闭角型青光眼者或属于易发作闭角型青光眼； 4)中枢神经系统处于抑制状态的急性酒精中毒者； 5)既往或现存在呼吸抑制或梦游状态； 6)对本品和辅料（乳糖、玉米淀粉、羟丙纤维素、硬脂酸镁）中任何成份过敏或不能耐受者，以及对其他苯二氮?类药物过敏或有药物食物或其他过敏史者； 7)不能遵守统一饮食或有吞咽困难者； 8)既往长期饮用过量（一天8杯以上，1杯=200 mL）茶、咖啡或含咖啡因的饮料者； 9)筛选前3个月内有嗜酒史，即每周饮酒量大于14单位(1单位=17.7mL乙醇，即1单位=357mL酒精量为5%的啤酒或43mL酒精量为40%的白酒或147mL酒精量为12%的葡萄酒）者；或研究期间不能禁酒者； 10)筛选前2周内使用任何处方或非处方药物者（包括化药、含药化妆品、保健品、中草药/中成药）； 11)筛选前3个月内每日吸烟量≥5支，或试验期间不能停止使用任何烟草类产品者； 12)筛选前3个月内参加了任何药物临床试验者； 13)筛选前4周内接受过疫苗接种者，或在研究期间计划接种疫苗者； 14)过去五年内有药物滥用史，或筛选前3个月内使用过毒品者； 15)筛选前3个月内献血或失血≥200mL，或计划在研究期间或研究结束后3个月内献血或血液成分者； 16)妊娠期、哺乳期女性或计划在试验期间怀孕的女性，以及女性受试者在签署知情同意书前1个月至给药后3个月内有生育计划，不愿采取有效避孕措施或有捐卵计划者；男性受试者在试验期间及给药后3个月内有生育计划，不愿采取有效避孕措施或有捐精计划者； 17)女性受试者筛选前14天内进行过无防护性性行为者； 18)有晕针或晕血史；或对穿刺采血疼痛不耐受； 19)研究期间及研究结束后1周内有机械操作、驾驶需要者； 20)研究者认为受试者不宜参加试验，或受试者因自身原因不能参加试验。

Exclusion criteria：

1. Physical examination, vital sign measurement, electrocardiogram examination, and laboratory tests during the screening period, including [blood routine, urine routine, blood biochemistry, coagulation function examination, pregnancy examination (only for female subjects), serum virology examination], and the investigator judges that the abnormality is clinically significant; 2. Patients with a history of any clinically serious diseases such as respiratory system (including cor pulmonale, emphysema, and bronchial asthma), digestive system (with special attention to those with severe diarrhea in the week before the trial), cardiovascular system, blood and lymphatic system, psychiatric and nervous system (with special attention to the history of epilepsy), genitourinary system, endocrine system, liver, kidney, and metabolic abnormalities (including those with major diseases or major surgeries within 1 year before dosing) or any other disease history or physiological condition that can interfere with the test results; 3. Those who are currently suffering from the following diseases: myasthenia gravis, severe chronic obstructive pulmonary disease, acute angle-closure glaucoma, or angle-closure glaucoma; 4. Acute alcoholism with central nervous system suppression; 5. Past or existing respiratory depression or sleepwalking; 6. Those who are allergic to or intolerant to any of the ingredients in this product and excipients (lactose, corn starch, hydroxypropylcellulose, magnesium stearate), as well as those who are allergic to other benzodiazepines or have a history of drug, food or other allergies; 7. Those who cannot follow the uniform diet or have difficulty swallowing; 8. Those who have consumed too much tea, coffee or caffeinated beverages for a long time (more than 8 cups a day, 1 cup = 200 mL) in the past; 9. Those who have a history of alcohol addiction within 3 months before screening, that is, those who drink more than 14 units per week (1 unit = 17.7mL ethanol, that is, 1 unit = 357mL of beer with 5% alcohol or 43mL of liquor with 40% alcohol or 147mL of wine with 12% alcohol); or those who cannot abstain from alcohol during the study period; 10. Those who have used any prescription or over-the-counter drugs (including chemical drugs, medicated cosmetics, health care products, Chinese herbal medicines/Chinese patent medicines) within 2 weeks before screening; 11. Those who smoked ≥ 5 cigarettes per day within 3 months before screening, or could not stop using any tobacco products during the trial; 12. Those who have participated in any drug clinical trial within 3 months before screening; 13. Those who have received vaccination within 4 weeks before screening, or those who plan to be vaccinated during the study period; 14. Those who have a history of drug abuse in the past five years, or have used drugs within 3 months before screening; 15. Those who donate or lose 200mL of blood or blood loss within 3 months before screening, or plan to donate blood or blood components during the study period or within 3 months after the end ≥of the study; 16. Pregnant, lactating females or females who plan to become pregnant during the trial, as well as female subjects who have a birth plan from 1 month before signing the informed consent form to 3 months after dosing, and are unwilling to take effective contraceptive measures or have an egg donation plan; Male subjects who have a fertility plan during the trial period and within 3 months after dosing, and are unwilling to take effective contraceptive measures or have sperm donation plans; 17. Female subjects who have had unprotected sex within 14 days before screening; 18. Have a history of fainting or blood sickness;or intolerance to pain in puncture blood collection; 19. Those who require mechanical operation or driving during the research period and within one week after the completion of the research; 20. Researchers believe that participants are not suitable to participate in the trial, or that participants are unable to participate due to their own reasons.

研究实施时间：

Study execute time：

从 From 2025-02-10 00:00:00至 To 2026-02-10 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-02-10 00:00:00 至 To 2025-05-10 00:00:00

干预措施：

Interventions：

组别：

餐后试验：T-R组

样本量：

 12

Group：

Post meal test: T-R group

Sample size：

干预措施：

进餐后30min口服受试制剂1mg，10天后交叉给药，进餐后30min口服参比制剂1mg。

干预措施代码：

Intervention：

Take 1mg of the test formulation orally 30 minutes after meals, cross administer 10 days later, and take 1mg of the reference formulation orally 30 minutes after meals.

Intervention code：

组别：

餐后试验：R-T组

样本量：

 12

Group：

Post meal test: R-T group

Sample size：

干预措施：

进餐后30min口服参比制剂1mg，10天后交叉给药，进餐后30min口服受试制剂1mg。

干预措施代码：

Intervention：

Take 1mg of the reference preparation orally 30 minutes after meals, cross administer 10 days later, and take 1mg of the test preparation orally 30 minutes after meals.

Intervention code：

组别：

空腹试验：T-R组

样本量：

 12

Group：

Fasting test: T-R group

Sample size：

干预措施：

空腹状态下口服受试制剂1mg，10天后交叉给药，空腹状态下口服参比制剂1mg。

干预措施代码：

Intervention：

Oral administration of 1mg of the test formulation on an empty stomach, cross administration after 10 days, and oral administration of 1mg of the reference formulation on an empty stomach.

Intervention code：

组别：

空腹试验：R-T组

样本量：

 12

Group：

Fasting test: R-T group

Sample size：

干预措施：

空腹状态下口服参比制剂1mg，10天后交叉给药，空腹状态下口服受试制剂1mg。

干预措施代码：

Intervention：

Take 1mg of the reference preparation orally on an empty stomach, cross administer after 10 days, and take 1mg of the test preparation orally on an empty stomach.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河北 

市(区县)：

  

Country：

China

Province：

Hebei

City：

单位(医院)：

 河北大学附属医院 

单位级别：

 三级甲等 

Institution
hospital：

Affiliated Hospital of Hebei University

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：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

AUC0-t

指标类型：

主要指标

Outcome：

AUC0-t

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

AUC0-∞

指标类型：

主要指标

Outcome：

AUC0-∞

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

达峰时间

指标类型：

次要指标

Outcome：

Tmax

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

半衰期

指标类型：

次要指标

Outcome：

t1/2

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：

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：

正在进行

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）：

随机表由统计单位应用SAS（9.4或以上版本）的PLAN过程按1:1区组随机产生。

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

Random tables are randomly generated by the statistical unit applying the PLAN process of SAS (version 9.4 or later) on a 1:1 basis.

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

Blinding：

Open-label study

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）：

研究公开发表后半年，邮件联系研究负责人获取。

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

Six months after the publication of the research, contact the research leader via email to obtain it.

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：

电子数据收集系统

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

EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2025-02-13 08:47:33