ChiCTR2200062883 版本V1.0 版本创建时间2022/08/22 16:58:13 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：

 ChiCTR2200062883 

最近更新日期：

Date of Last Refreshed on：

 2022-08-22 16:57:30 

注册时间：

Date of Registration：

 2022-08-22 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

阿莫西林克拉维酸钾片（0.375g）在健康受试者中开放、随机、三周期、三序列、三交叉空腹及餐后状态下的 生物等效性研究

Public title：

Bioequivalence study of amoxicillin-clavulanate potassium tablets (0.375g) in healthy subjects in open, randomized, three-cycle, three-sequence, three-crossover fasting and postprandial states

注册题目简写：

English Acronym：

研究课题的正式科学名称：

阿莫西林克拉维酸钾片（0.375g）在健康受试者中开放、随机、三周期、三序列、三交叉空腹及餐后状态下的 生物等效性研究

Scientific title：

Bioequivalence study of amoxicillin-clavulanate potassium tablets (0.375g) in healthy subjects in open, randomized, three-cycle, three-sequence, three-crossover fasting and postprandial states

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：

刘献芳 

研究负责人：

郭风雪 

Applicant：

Liu Xianfang 

Study leader：

Guo Fengxue 

申请注册联系人电话：

Applicant telephone：

 18632096620

研究负责人电话：

Study leader's
telephone：

17731998618

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：

 1511494359@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 gfx0266@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：

河北省邢台市桥西区钢铁北路618号

研究负责人通讯地址：

河北省邢台市桥西区钢铁北路618号

Applicant address：

618 Iron and Steel Road North, Qiaoxi District, Xingtai, Hebei, China

Study leader's address：

618 Iron and Steel Road North, Qiaoxi District, Xingtai, Hebei, China

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：

邢台医专第二附属医院

Applicant's institution：

The Second Affiliated Hospital of Xingtai Medical College

研究负责人所在单位：

Affiliation of the Leader：

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：

 XYEYCTEC-HS-105

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：

邢台医学高等专科学校第二附属医院临床试验伦理委员会

Name of the ethic committee：

Clinical Trial Ethics Committee of the Second Affiliated Hospital of Xingtai Medical College

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-06-02 00:00:00

伦理委员会联系人：

柳振芳

Contact Name of the ethic committee：

Liu zhenfang

伦理委员会联系地址：

河北省邢台市信都区钢铁北路618号

Contact Address of the ethic committee：

618 Iron and Steel Road North , Xindu District, Xingtai, Hebei,China

伦理委员会联系人电话：

Contact phone of the ethic committee：

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：

邢台医专第二附属医院

Primary sponsor：

The Second Affiliated Hospital of Xingtai Medical College

研究实施负责（组长）单位地址：

河北省邢台市信都区钢铁北路618号

Primary sponsor's address：

618 Iron and Steel Road North , Xindu District, Xingtai, Hebei,China

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)：

邢台

Country：

China

Province：

Hebei

City：

Xingtai

单位(医院)：

邢台医专第二附属医院

具体地址：

信都区钢铁北路618号

Institution
hospital：

The Second Affiliated Hospital of Xingtai Medical College

Address：

618 Iron and Steel Road North, Xindu District

经费或物资来源：

珠海联邦制药股份有限公司中山分公司

Source(s) of funding：

Zhuhai United Laboratories(Zhongshan) Co.

研究疾病：

适用于敏感菌引起的各种感染  

Target disease：

Suitable forvarious infections caused by sensitive bacteria

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： 本研究以珠海联邦制药股份有限公司中山分公司生产的阿莫西林克拉维酸钾片（0.375 g/片）为受试制剂，原研厂家英国Beecham Group Plc公司生产的阿莫西林克拉维酸钾片（0.375 g/片）（商品名：Augmentin?）为参比制剂，研究受试制剂和参比制剂在健康受试者空腹及餐后条件下的药代动力学特征，并评价两制剂的人体生物等效性。 次要目的： 观察健康受试者口服受试制剂和参比制剂的安全性。  

Objectives of Study：

main purpose: In this study, Amoxicillin-Clavulanate Potassium Tablets (0.375 g/tablet) produced by Zhuhai United Laboratories Co., Ltd. Zhongshan Branch was used as the test preparation, and the original manufacturer was Amoxicillin-Clavulanate Potassium Tablets produced by Beecham Group Plc in the United Kingdom. (0.375 g/tablet) (trade name: Augmentin?) is the reference preparation, to study the pharmacokinetic characteristics of the test preparation and the reference preparation under fasting and postprandial conditions in healthy subjects, and to evaluate the human body of the two preparations. Bioequivalence. Secondary purpose: Observe the safety of oral test preparations and reference preparations 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：

满足以下所有标准才能入组：
1）年龄为18~45周岁（包括18周岁和45周岁）的健康男性和女性受试者；
2）体重：男性受试者不应低于50 kg，女性受试者不应低于45 kg，体重指数【BMI=体重（kg）/身高2（m2）】在19.0～26.0 kg/m2范围内（包括边界值）；
3）筛选期体格检查、生命体征、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）、乙肝表面抗原、丙肝抗体、梅毒螺旋体抗体、艾滋病病毒抗体，结果正常或被研究者判断异常无临床意义者；
4）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；
5）受试者能够与研究者作良好的沟通并能够依照研究规定完成研究。

Inclusion criteria

All of the following criteria are met to be included in the group:
1) Healthy male and female subjects aged 18 to 45 (including 18 and 45);
2) Body weight: male subjects should not be less than 50 kg, female subjects should not be less than 45 kg, and the body mass index [BMI=weight (kg)/height 2 (m2)] should be in the range of 19.0 to 26.0 kg/m2 within (including boundary values);
3) During the screening period, physical examination, vital signs, electrocardiogram, laboratory tests (including blood routine, urine routine, blood biochemistry, coagulation function), hepatitis B surface antigen, hepatitis C antibody, Treponema pallidum antibody, HIV antibody, the results were normal or were The investigator judges that the abnormality has no clinical significance;
4) Subjects fully understand the purpose, nature, methods and possible adverse reactions of the trial, volunteer as subjects, and sign an informed consent form before any research procedure begins;
5) The subjects can communicate well with the researcher and can complete the research in accordance with the research regulations.

排除标准：

凡是出现下列情况之一者不能入选本试验：
1）过敏体质或有食物、药物过敏史，尤其是已知对头孢类、青霉素类产品及其辅料中任何成份过敏者或青霉素皮试阳性者；
2）研究者判断具有临床意义的急、慢性消化道疾病和肝、肾、内分泌、心血管、神经、精神、肺、肿瘤、免疫、血液或代谢紊乱等疾病或任何其它疾病，或具有这些疾病的病史者若参加试验将危害其安全或影响研究结果者；
3）在筛选前3个月内接受过手术，或者计划在研究期间进行手术者，及凡接受过会影响药物吸收、分布、代谢、排泄的手术者；
4）血管穿刺条件差，不能耐受静脉穿刺者，有晕针或晕血史者；
5）乳糖不耐受者（曾发生过喝牛奶腹泻者）；
6）给药前6个月内有药物滥用史者，或尿药筛查阳性者；
7）筛选前3个月内献血或大量失血（大于400 mL），接受输血或使用血制品者；
8）妊娠或哺乳期妇女，以及男性受试者（或其伴侣）或女性受试者在给药前2周至研究结束后6个月内有妊娠计划，不愿采取充分有效的的避孕措施（具体避孕措施见附录1），或有捐精或捐卵计划者；
9）在服用研究药物前28天内使用过任何抑制或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、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、大环内酯类、硝基咪唑类、镇静催眠药、维拉帕米、氟喹诺酮类、抗组胺类），或CYP3A4、P-gp的诱导剂（如利福平）者；
10）给药前2周内使用任何处方药、中草药、非处方药、保健品和功能性维生素者；
11）筛选前3个月内平均每日吸烟量大于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个月内每周饮酒量大于14单位（1单位酒精≈360 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者；
13）酒精呼气试验结果大于0.0 mg/100 mL者；
14）在筛选前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=250 mL）者；
15）在服用研究药物前14天内食用过火龙果、芒果、柚子、酸橙、杨桃或由其制备的食物或饮料者；
16）在服用研究药物前48 h内食用过巧克力、任何含咖啡因、含黄嘌呤的食物或饮料等影响药物吸收、分布、代谢、排泄的特殊饮食者；
17）试验前3个月内，参加过其他药物临床试验且使用过试验用药者；
18）不能遵守统一饮食（如对高脂餐食物不耐受等）或有吞咽困难者；
19）筛选前4周内接种过任何疫苗者；
20）研究者认为不宜参加试验者。

Exclusion criteria：

Anyone who has one of the following conditions cannot be included in this trial:
1) Allergic constitution or a history of food or drug allergy, especially those who are known to be allergic to any of the ingredients in cephalosporins, penicillin products and their excipients, or those with a positive penicillin skin test;
2) Acute and chronic digestive tract diseases, liver, kidney, endocrine, cardiovascular, neurological, mental, lung, tumor, immune, blood or metabolic disorders or any other diseases or any other diseases judged by the investigator to have clinical significance, or have these diseases Those with a medical history who will jeopardize their safety or affect the results of the study if they participate in the trial;
3) Those who have undergone surgery within 3 months before screening, or who plan to undergo surgery during the study period, and those who have undergone surgery that will affect drug absorption, distribution, metabolism, and excretion;
4) Those with poor vascular puncture conditions, unable to tolerate venipuncture, and those with a history of needle fainting or haemorrhage;
5) Lactose intolerance (those who have had milk diarrhea);
6) Those with a history of drug abuse within 6 months before administration, or those with positive urine drug screening;
7) Those who donated blood or lost a large amount of blood (more than 400 mL), received blood transfusion or used blood products within 3 months before screening;
8) Pregnant or lactating women, as well as male subjects (or their partners) or female subjects who have a pregnancy plan within 2 weeks before administration to 6 months after the end of the study, are unwilling to take adequate and effective contraceptive measures ( For specific contraceptive measures, see Appendix 1), or have sperm or egg donation plans;
9) Have used any drugs that inhibit or induce liver metabolism of drugs within 28 days before taking the study drug (such as: inducers - barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors) --SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines), or CYP3A4, P- gp inducers (such as rifampicin);
10) Those who use any prescription drugs, Chinese herbal medicines, over-the-counter drugs, health products and functional vitamins within 2 weeks before administration;
11) Those who smoked more than 5 cigarettes on average per day in the 3 months before screening, or who could not stop using any tobacco products during the trial;
12) Drink more than 14 units per week within 3 months before screening (1 unit of alcohol ≈ 360 mL of beer or 45 mL of spirits with an alcohol content of 40% or 150 mL of wine), or those who cannot abstain from alcohol during the test;
13) Alcohol breath test results greater than 0.0 mg/100 mL;
14) Those who drink excessive tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup = 250 mL) every day within 3 months before screening;
15) Those who have consumed dragon fruit, mango, grapefruit, lime, star fruit or food or drink prepared from them within 14 days before taking the study drug;
16) Those who have eaten chocolate, any food or drink containing caffeine or xanthine within 48 hours before taking the study drug and other special diets that affect the absorption, distribution, metabolism and excretion of the drug;
17) Those who have participated in clinical trials of other drugs and have used experimental drugs within 3 months before the trial;
18) Those who cannot follow a unified diet (such as intolerance to high-fat meals, etc.) or have difficulty swallowing;
19) Those who have received any vaccine within 4 weeks before screening;
20) Those who are deemed unsuitable by the investigator to participate in the trial.

研究实施时间：

Study execute time：

从 From 2022-08-23 00:00:00至 To 2022-10-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-08-23 00:00:00 至 To 2022-10-31 00:00:00

干预措施：

Interventions：

组别：

A组

样本量：

 16

Group：

Agroup

Sample size：

干预措施：

TRR

干预措施代码：

Intervention：

TRR

Intervention code：

组别：

B组

样本量：

 16

Group：

Bgroup

Sample size：

干预措施：

RTR

干预措施代码：

Intervention：

RTR

Intervention code：

组别：

C组

样本量：

 16

Group：

Cgroup

Sample size：

干预措施：

RRT

干预措施代码：

Intervention：

RRT

Intervention code：

组别：

D组

样本量：

 16

Group：

D group

Sample size：

干预措施：

TRR

干预措施代码：

Intervention：

TRR

Intervention code：

组别：

E组

样本量：

 16

Group：

E group

Sample size：

干预措施：

RTR

干预措施代码：

Intervention：

RTR

Intervention code：

组别：

F组

样本量：

 16

Group：

F group

Sample size：

干预措施：

RRT

干预措施代码：

Intervention：

RRT

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)：

 邢台 

Country：

China

Province：

Hebei

City：

Xingtai

单位(医院)：

 邢台医专第二附属医院 

单位级别：

 三级 

Institution
hospital：

The Second Affiliated Hospital of Xingtai Medical College

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

最大血药浓度

指标类型：

主要指标

Outcome：

Maximum blood 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：

从0点到最后一个时间点t的血药浓度—时间曲线下面积

指标类型：

主要指标

Outcome：

Area under the blood drug concentration-time curve from 0 to the last time point T

Type：

Primary 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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 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）：

用SAS V9.4及以上版本的PLAN过程产生受试者随机表。采用区组随机方法，空腹试验受试者按照1:1:1的比例随机分配到三组A组、B组、C组中的某一组，餐后试验受试者按照1:1:1的比例随机分配到三组D组、E组、F组中的某一组。随机化结果中应保留随机化种子，以保证随机化结果的重现性。

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

The randomization table of subjects was generated using the PLAN procedure of SAS V9.4 and above. Using the block random method, subjects in the fasting test were randomly assigned to one of the three groups A, B, and C according to the ratio of 1:1:1, and the subjects in the postprandial 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：

Blinding：

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）：

邢台医专第二附属医院。

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

The Second Affiliated Hospital of Xingtai Medical College.

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：

数据管理员根据试验方案设计构建eCRF，并根据逻辑核查计划（DVP）设置逻辑核查，通过测试并获申办方批准后发布使用。

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

The data administrator builds the eCRF according to the design of the trial protocol, sets up logical verification according to the logical verification plan (DVP), and releases it for use after passing the test and being approved by the sponsor.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2022-08-22 16:57:31