ChiCTR2300071630 版本V1.0 版本创建时间2023/05/19 16:20:17 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：

ChiCTR2300071630 

最近更新日期：

Date of Last Refreshed on：

2023-05-19 16:20:10 

注册时间：

Date of Registration：

2023-05-19 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

阿奇霉素片在健康受试者中随机、开放、两制剂、三周期、三序列、 部分重复交叉设计、空腹和餐后状态下的生物等效性试验临床研究计划及研究方案

Public title：

Clinical study plan and protocol of randomized, open, two dose, three cycle, three sequence, partially repeated crossover design, fasting and postprandial bioequivalence trials of azithromycin tablets in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

阿奇霉素片在健康受试者中随机、开放、两制剂、三周期、三序列、 部分重复交叉设计、空腹和餐后状态下的生物等效性试验临床研究计划及研究方案

Scientific title：

Clinical study plan and protocol of randomized, open, two dose, three cycle, three sequence, partially repeated crossover design, fasting and postprandial bioequivalence trials of azithromycin tablets in 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：

杨哲 

研究负责人：

杨水新 

Applicant：

Yangzhe 

Study leader：

Yang Shuixin 

申请注册联系人电话：

Applicant telephone：

+86 188 5109 1099

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：

njyangzhe@163.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：

No. 1558, Sanhuan North Road, Wuxing District, Huzhou City, Zhejiang Province

Study leader's address：

No. 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：

浙江省湖州市中心医院

Applicant's institution：

Huzhou Central Hospital, Zhejiang Province

研究负责人所在单位：

浙江省湖州市中心医院

Affiliation of the Leader：

Huzhou Central Hospital, Zhejiang Province

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：

2020-019-03

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：

湖州市中心医院药物临床试验伦理委员会

Name of the ethic committee：

Drug Clinical Trial Ethics Committee of Huzhou Central Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2020-12-14 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：

No. 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：

浙江省湖州市中心医院

Primary sponsor：

Huzhou Central Hospital, Zhejiang Province

研究实施负责（组长）单位地址：

浙江省湖州市中心医院

Primary sponsor's address：

Huzhou Central Hospital, 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)：

河北

市(区县)：

石家庄

Country：

China

Province：

Hebei

City：

Shijiazhuang

单位(医院)：

石家庄四药有限公司

具体地址：

河北省石家庄市裕华区漓江道 333 号

Institution
hospital：

Shijiazhuang Four Drugs Co., Ltd

Address：

No. 333 Lijiang Road, Yuhua District, Shijiazhuang City, Hebei Province

经费或物资来源：

石家庄四药有限公司

Source(s) of funding：

Shijiazhuang Four Drugs Co., Ltd

Target disease：

Antibacterial treatment

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：

主要研究目的： 研究空腹和餐后状态下单次口服受试制剂阿奇霉素片（规格： 0.25g， 石家庄四药有限公司生产）与参比制剂阿奇霉素片（ ZITHROMAX，规格：0.25g， PfizerLaboratories Div Pfizer Inc 生产）在健康成年受试者体内的药代动力学，评价空腹和餐后状态下口服两种制剂的生物等效性。 次要研究目的： 评价单次口服受试制剂阿奇霉素片（ 0.25g）或参比制剂阿奇霉素片（商品名：ZITHROMAX， 0.25mg）在健康受试者中的安全性。  

Objectives of Study：

Main research purposes: Study on single oral administration of the test preparation azithromycin tablets (specification: 0.25g, Shijiazhuang No.4 Pharmaceutical) under fasting and postprandial conditionsLtd.) and reference preparation azithromycin tablets (ZITHROMAX, Specification: 0.25g, PfizerLaboratory Div Pfizer Inc) in healthy adult subjects, evaluating the pharmacokinetics of fasting andThe bioequivalence of the two preparations taken orally in the postprandial state. Secondary study purpose: Evaluation of single oral administration of the test formulation azithromycin tablets (0.25 g) or the reference formulation azithromycin tablets (trade name: ZITHROMAX, 0.25 mg) 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. 受试者充分了解试验目的、性质、方法以及可能发生的不良反应，自愿作为受试者，并在任何研究程序开始前签署知情同意书； 2. 年龄为 18~65 岁（包括 18 岁和 65 岁）的男性和女性受试者； 3. 男性体重≥50.0 kg，女性体重≥45.0 kg，体重指数（BMI）在 19.0~26.0 kg/m2范围内（包括临界值） ； 4. 受试者无心血管、肝脏、肾脏、血液和淋巴、内分泌、免疫、精神、神经、胃肠道系统等慢性疾病史或严重疾病史，并且总体健康状况良好； 5. 生命体征检查、体格检查、临床实验室检查（血常规、尿常规、血生化、 传染病筛查、凝血功能、妊娠检查（女性））、 12 导联心电图、尿液药物筛查及酒精呼气试验，结果显示无异常或异常无临床意义者； 不符合上述条件之一者，不得作为志愿受试者入选。

Inclusion criteria

1. The subject fully understands the purpose, nature, method, and possible adverse reactions of the test, and voluntarily acts as a subject, and sign an informed consent form before any research procedure begins; 2. Male and female subjects aged 18 to 65 years (including 18 and 65 years); 3. Male weight ≥ 50.0 kg, female weight ≥ 45.0 kg, body mass index (BMI) between 19.0 and 26.0 kg/m2 (including critical values); 4. The subject has no history of chronic or serious diseases such as cardiovascular, liver, kidney, blood and lymph, endocrine, immune, mental, neurological, or gastrointestinal system, and overall good health; 5. Vital sign examination, physical examination, clinical laboratory examination (blood routine, urine routine, blood biochemistry, infection disease screening, coagulation function, pregnancy test (female), 12-lead electrocardiogram, urine drug screening and alcohol breath test, the result shows no abnormality or no clinical significance; Those who do not meet one of the above conditions shall not be selected as voluntary subjects.

排除标准：

1. 对阿奇霉素及阿奇霉素片任何药物组分有过敏史，或已知对红霉素、 大环内酯类以及酮内酯类药物过敏，或曾出现对两种或两种以上药物或食物过敏者； 2. 有吞咽困难或任何影响药物吸收的胃肠道疾病史者； 3. 曾经出现过有临床意义的关节痛、 荨麻疹、血管神经性水肿等疾病，或者曾经出现任何增加出血性风险的疾病（如颅内出血、胃肠道出血或穿孔、具有临床意义的血小板减少症、凝血功能障碍等）者； 4. 任何经研究医生判定有临床意义，可能影响试验安全性或药物体内代谢过程的手术史、外伤史者，或者计划在试验期间（自签署知情同意书至第三周期出院）进行手术者； 5. 筛选前2周内使用过任何药品（包括处方药、非处方药、中草药等）或者保健品者； 6. 筛选前 30 天内接受过疫苗接种者； 7. 筛选前30天内使用过任何抑制/诱导肝脏对药物代谢的药物（如：诱导剂--巴比妥类、卡马西平、苯妥英钠、糖皮质激素、奥美拉唑；抑制剂--SSRI类抗抑郁药、西咪替丁、地尔硫卓、硝基咪唑类、镇静催眠药、维拉帕米、氟喹诺酮类、抗组胺类）；或任何改变胃肠道环境的药物（如：质子泵抑制剂泰妥拉唑、奥美拉唑、兰索拉唑、埃索拉唑等； H2拮抗剂雷尼替丁、西咪替丁、法莫替丁等；抗酸剂碳酸氢钠、氧化镁、氢氧化铝、三硅酸镁等；胃黏膜保护剂硫糖铝等）；或任何与本品有药物相互作用的药物者； 8. 筛选前6个月内有药物滥用史者； 9. 筛选前6个月内使用过毒品者； 10. 筛选前3个月内每日吸烟量大于5支，或试验期间（自签署知情同意书至第三周期出院） 不同意停止吸烟或食用任何含烟草类的食物者； 11. 筛选前3个月内每周饮酒量大于14单位（1单位=17.7mL乙醇，即1单位= 357 mL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），或试验期间（自签署知情同意书至第三周期出院） 不同意停止饮酒或食用任何含酒精类的食物者； 12. 筛选前3个月内每天饮用过量茶、咖啡和/或富含咖啡因的饮料（ 8 杯以上， 1杯=250 ml） ， 或试验期间（自签署知情同意书至第三周期出院） 不同意停止食用茶、 咖啡和/或富含咖啡因的食物或饮料（包括巧克力、可乐等） 者； 13. 在试验开始服药前7天内服用过含有可诱导或抑制肝脏代谢酶的食物（如西柚、葡萄柚、酸橙等）及其制备的食物或饮料，或试验期间（自签署知情同意书至第三周期出院）不同意停止食用此类食物者； 14. 筛选前3个月内献血包括成分血或大量失血（≥400mL， 规律月经失血除外）， 接受输血或使用血制品者，或试验期间（自签署知情同意书至第三周期出院） 计划献血者； 15. 筛选前30天内已经开始了显著不正常的饮食（如高钾、低脂、节食、低钠等）； 16. 给药前3个月内参加过其他的药物临床试验（成功入组） 或非本人来参加临床 试验者； 17. 不能耐受静脉穿刺者， 经研究者评估采血困难者，有晕针晕血史者； 18. 乳糖不耐受者（曾发生过喝牛奶腹泻者，适用于餐后试验）； 19. 对饮食有特殊要求，不能接受统一饮食者； 20. 女性受试者自筛选前两周（男性受试者自第一次给药后）至研究药物最后一次 给药后6个月内有妊娠计划且不愿采取有效的避孕措施， 或 捐卵（捐精） 计划者； 21. 受试者（女性）处在哺乳期者； 22. 入住时酒精呼气试验结果大于0.0mg/100ml者； 23. 入住时尿液药物筛查阳性者（吗啡、甲基安非他明、氯胺酮、二亚甲基双氧安非他明、四氢大麻酚酸、可卡因）； 24. 在使用试验药物前发生急性疾病者； 25. 其它研究者判定不适宜参加的受试者。

Exclusion criteria：

1. Persons who have a history of allergy to azithromycin and any drug component of azithromycin tablets, or are known to be allergic to erythromycin, macrolides, and ketolactones, or have experienced allergies to two or more drugs or foods; 2. Have a history of swallowing difficulties or any gastrointestinal diseases that affect drug absorption; 3. Those who have experienced clinically significant diseases such as arthralgia, urticaria, angioneurotic edema, or any diseases that increase the risk of bleeding (such as intracranial hemorrhage, gastrointestinal bleeding or perforation, clinically significant thrombocytopenia, coagulation dysfunction, etc.); 4. Any person with a history of surgery or trauma that has been determined by the research doctor to be clinically significant and may affect the safety of the trial or the metabolic process of the drug in vivo, or who plans to undergo surgery during the trial period (from signing the informed consent form to discharge in the third cycle); 5. Those who have used any drugs (including prescription drugs, non prescription drugs, Chinese herbal medicines, etc.) or health products within 2 weeks before screening; 6. Those who have received vaccine within 30 days before screening; 7. Have used any drugs that inhibit/induce liver metabolism of drugs within 30 days before screening (such as: inducers - barbiturates, carbamazepine, phenytoin sodium, glucocorticoids, omeprazole; inhibitors - SSRI antidepressants, cimetidine, diltiazem, nitroimidazoles, sedative hypnotics, verapamil, fluoroquinolones, antihistamines); Or any drug that alters the gastrointestinal environment (such as proton pump inhibitors such as tetoprazole, omeprazole, lansoprazole, esomeprazole, etc.; H2 antagonists ranitidine, cimetidine, famotidine, etc.; antacid agents such as sodium bicarbonate, magnesium oxide, aluminum hydroxide, magnesium trisilicate, etc.; gastric mucosal protective agent sucralfate, etc.); Or any drug that has drug interactions with this product; 8. Screening for persons with a history of drug abuse within the previous 6 months; 9. Screening for those who have used drugs within the previous 6 months; 10. Those who smoke more than 5 cigarettes per day within 3 months before screening, or who do not agree to stop smoking or consume any food containing tobacco during the trial period (from signing the informed consent form to discharge in the third cycle); 11. Those who drink more than 14 units (1 unit=17.7mL ethanol, that is, 1 unit=357mL beer with 5% alcohol, 43mL Baijiu with 40% alcohol, or 147mL wine with 12% alcohol) per week within 3 months before screening, or do not agree to stop drinking or eat any alcoholic food during the test period (from signing the informed consent form to discharge in the third cycle); 12. Those who consumed excessive amounts of tea, coffee, and/or caffeine-rich beverages (more than 8 cups, 1 cup=250 ml) every day within 3 months before screening, or who did not agree to stop consuming tea, coffee, and/or caffeine-rich foods or beverages (including chocolate, cola, etc.) during the trial period (from signing the informed consent form to discharge in the third cycle); 13. Those who have taken foods containing enzymes that can induce or inhibit liver metabolism (such as grapefruit, grapefruit, lime, etc.) and prepared foods or beverages within 7 days before the start of the trial, or who do not agree to stop eating such foods during the trial period (from signing the informed consent form to discharge in the third cycle); 14. Blood donation within 3 months before screening includes component blood or massive blood loss (≥ 400mL, excluding regular menstrual blood loss), persons receiving blood transfusion or using blood products, or planed to donate blood during the trial period (from signing the informed consent form to discharge in the third cycle); 15. Within 30 days before screening, a significantly abnormal diet (such as high potassium, low fat, diet, low sodium, etc.) has been started; 16. Participated in other drug clinical trials (successfully enrolled) or participated in clinical trials not in person; 17. Those who cannot tolerate intravenous puncture, have difficulty collecting blood as assessed by the researcher, and have a history of needle and blood syncope; 18. Lactose intolerance (those who have experienced diarrhea due to drinking milk, suitable for postprandial testing); 19. Those who have special dietary requirements and cannot accept a unified diet; 20. From two weeks before screening for female subjects (after the first administration for male subjects) to the last time of study medication have a pregnancy plan within 6 months after administration and are unwilling to take effective contraceptive measures, or egg donation (sperm donation) planners; 21. The subject (female) is in the lactation period; 22. Those with alcohol breath test results greater than 0.0mg/100ml at check-in; 23. Those who were positive for urine drug screening at the time of check-in (morphine, methamphetamine, ketamine, dimethylenedioxyamphetamine, tetrahydrocannabinoid acid, cocaine); 24. Those who develop acute illness before using the investigational drug; 25. Subjects were deemed unsuitable to participate by researchers due to other reasons.

研究实施时间：

Study execute time：

从 From 2020-10-01 00:00:00至 To 2021-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2021-03-04 00:00:00 至 To 2021-06-10 00:00:00  

干预措施：

Interventions：

组别：

空腹T-R-R 组

样本量：

12

Group：

Fasting T-R-R group

Sample size：

干预措施：

受试者在第一周期服用受试制剂，第二、三周期服用参比制剂

干预措施代码：

Intervention：

Subjects took the test preparation in the first cycle, and took the reference preparation in the second and third cycles

Intervention code：

组别：

空腹R-T-R 组

样本量：

12

Group：

Fasting R-T-R 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，第三周期服用参比制剂

干预措施代码：

Intervention：

Subjects took the reference preparation in the first cycle, the test preparation in the second cycle, and the reference preparation in the third cycle

Intervention code：

组别：

空腹R-R-T组

样本量：

12

Group：

Fasting R-R-T group

Sample size：

干预措施：

受试者在第一周期、第二周期服用参比制剂，第三周期服用受试制剂

干预措施代码：

Intervention：

Subjects took the reference preparation in the first and second cycles, and took the test preparation in the third cycle

Intervention code：

组别：

餐后T-R-R 组

样本量：

12

Group：

Postprandial T-R-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、三周期服用参比制剂

干预措施代码：

Intervention：

In the postprandial state, the subjects took the test preparation in the first cycle and took the reference preparation in the second and third cycles

Intervention code：

组别：

餐后R-T-R 组

样本量：

12

Group：

Postprandial R-T-R group

Sample size：

干预措施：

餐后状态下，受试者在第一周期服用参比制剂，第二周期服用受试制剂，第三周期服用参比制剂

干预措施代码：

Intervention：

In the postprandial state, subjects took the reference preparation in the first cycle, the test preparation in the second cycle, and the reference preparation in the third cycle

Intervention code：

组别：

餐后R-R-T组

样本量：

12

Group：

Postprandial R-R-T group

Sample size：

干预措施：

餐后状态下，受试者在第一周期、第二周期服用参比制剂，第三周期服用受试制剂

干预措施代码：

Intervention：

In the postprandial state, subjects took the reference preparation in the first and second cycles, and took the test preparation in the third 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)：

 湖州 

Country：

China 

Province：

Zhejiang 

City：

Huzhou 

单位(医院)：

浙江省湖州市中心医院 

单位级别：

三级甲等 

Institution
hospital：

Huzhou Central Hospital, Zhejiang Province

Level of the institution：

Class III Grade A

测量指标：

Outcomes：

指标中文名：

血药浓度

指标类型：

主要指标

Outcome：

Plasma concentration

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

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：

从0时刻到可检测最低血药浓度的时间内曲线下面积

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：

从0时刻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：

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：

λz

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

消除终末端半衰期

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：

指标中文名：

残留面积百分比

指标类型：

次要指标

Outcome：

AUC_%Extrap

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：

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：

结束

/Completed

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）：

随机分组表由数据管理与统计分析单位产生，本次研究分空腹试验和餐后试验，均采用区组随机方法，让每位受试者随机分配至 T-R-R 组、 R-T-R 组或 R-R-T 组。 该随机数据具有重现性， 由 SAS 9.4 或更高版本产生的的空腹试验和餐后试验随机种子数需要保存。 为确保在数据统计分析前，生物样本检测分析人员将不获得受试者分组信息及随机给药信息， 空腹试验受试者随机表和餐后试验受试者随机表由随机统计师在试验开始之前直接传递给临床研究中心。

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

The random grouping table was generated by the data management and statistical analysis unit. This study was divided into fasting and postprandial trials, both using block randomization method. Each subject was randomly assigned to the T-R-R group, R-T-R group, or R-R-T group. The random data is reproducible, and the number of random seed for fasting test and postprandial test generated by SAS 9.4 or higher needs to be saved. In order to ensure that the biological sample detection and analysis personnel will not obtain the grouping information and random administration information of the subjects before the data statistical analysis, the random table of subjects in the fasting test and the random table of subjects in the postprandial test will be directly transmitted to the clinical research center by the random statistician before the start of the test.

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：

本次临床研究为开放性研究，除生物样本分析测试人员外，其他人员如临床研究者、项目管理人员、项目监查人员、数据管理及统计分析人员等均不设盲，为了客观的进行血药浓度的检测，分析测试人员采用盲态分析，采血管、冻存管上的标签不体现受试者所服用的试验药物类型（是受试制剂还是参比制剂）。

Blinding：

This clinical study is an open-ended study. Except for biological sample analysis and testing personnel, other personnel such as clinical researchers, project managers, project monitors, data management and statistical analysts are not blinded. In order to objectively detect blood drug concentration, the analysis and testing personnel use blind analysis, blood sampling The label on the frozen storage tube does not reflect the type of investigational drug taken by the subject (whether it is a test formulation or a reference formulation).

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）：

https://keytech.bioknow.net/

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

https://keytech.bioknow.net/

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：

电子采集和管理系统

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

(Electronic Data Capture, EDC)

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-05-19 16:20:10