ChiCTR2200055373 版本V1.1 版本创建时间2022/08/15 21:46:06 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：

 ChiCTR2200055373 

最近更新日期：

Date of Last Refreshed on：

 2022-08-15 21:21:41 

注册时间：

Date of Registration：

 2022-01-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

利丙双卡因乳膏在健康受试者中的单剂量、空腹、随机、开放、两周期、两交叉生物等效性研究

Public title：

A single-dose, fasting, randomized, open-label, two-cycle, two-crossover bioequivalence study of riprobicaine cream in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

利丙双卡因乳膏在健康受试者中的单剂量、空腹、随机、开放、两周期、两交叉生物等效性研究

Scientific title：

A single-dose, fasting, randomized, open-label, two-cycle, two-crossover bioequivalence study of riprobicaine cream 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：

孙泽旭 

研究负责人：

阳国平/项玉霞 

Applicant：

Sun Zexu 

Study leader：

Yang Guoping, Xiang Yuxia 

申请注册联系人电话：

Applicant telephone：

 +86 19375180485

研究负责人电话：

Study leader's
telephone：

+86 731 89918665

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：

 133110704@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 ygp9880@126.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：

湖南省长沙市岳麓区桐梓坡路138号

研究负责人通讯地址：

湖南省长沙市岳麓区桐梓坡路138号

Applicant address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

Study leader's address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

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：

中南大学湘雅三医院临床试验研究中心

Applicant's institution：

The Third Xiangya Hospital of Central South University

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：

 21272

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：

中南大学湘雅三医院伦理委员会

Name of the ethic committee：

The Third Xiangya Hospital of Central South University Ethics Committee

伦理委员会批准日期：

Date of approved by ethic committee：

 2021-12-14 00:00:00

伦理委员会联系人：

王晓敏

Contact Name of the ethic committee：

Wang Xiaomin

伦理委员会联系地址：

湖南省长沙市岳麓区桐梓坡路138号中南大学湘雅三医院伦理委员会

Contact Address of the ethic committee：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

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：

中南大学湘雅三医院临床试验研究中心

Primary sponsor：

The Third Xiangya Hospital of Central South University

研究实施负责（组长）单位地址：

湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

138 Tongzipo Road, Yuelu District, Changsha, Hu'nan

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖南

市(区县)：

长沙

Country：

China

Province：

Hu'nan

City：

Changsha

单位(医院)：

中南大学湘雅三医院临床试验研究中心

具体地址：

岳麓区桐梓坡路138号

Institution
hospital：

The Third Xiangya Hospital of Central South University

Address：

138 Tongzipo Road, Yuelu District

经费或物资来源：

长沙晶易医药科技股份有限公司

Source(s) of funding：

Changsha Jingyi Pharmaceutical Technology Co., Ltd

研究疾病：

局部麻醉  

Target disease：

local anesthesia

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：

 I期临床试验 

Study phase：

1

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

主要研究目的：本研究以河北亚东制药有限公司生产的利丙双卡因乳膏 5 g（1 g：利多卡因 25mg 和丙胺卡因 25mg）为受试制剂，以 AstraZeneca GmbH 生产的利丙双卡因乳膏 5 g（1 g：利多卡因 25 mg 和丙胺卡因 25 mg，商品名：EMLA?）为参比制剂，评价受试制剂和参比制剂在空腹条件下给药时的生物等效性。 次要研究目的：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：

Main research objectives: in this study, 5 g of lidocaine cream (1 g: lidocaine 25mg and prilocaine 25mg) produced by Hebei Yadong Pharmaceutical Co., Ltd. was used as the test preparation, and 5 g of lidocaine cream (1 g: lidocaine 25mg and prilocaine 25mg, trade name: EMLA) produced by AstraZeneca GmbH ?） As the reference preparation, evaluate the bioequivalence of the test preparation and the reference preparation when administered under fasting conditions. Secondary study objective: To observe the safety of test preparation and reference preparation 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：

受试者必须同时满足以下所有选项：
1）性别：男性和女性健康受试者；
2）年龄：18 周岁至 60 周岁（含边界值）的中国健康志愿者
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）双侧大腿前侧皮肤正常完整无破损；
5）受试者必须在试验前对本研究知情同意，并自愿签署书面的知情同意书；
6）受试者能够与研究者进行良好的沟通并能够依照研究规定完成研究。

Inclusion criteria

Subjects must meet all of the following options at the same time:
1) Gender: male and female healthy subjects;
2) Age: Chinese healthy volunteers aged 18 to 60 (including boundary value)
3) Weight: not less than 50.0 kg for male subjects and 45.0 kg for female subjects, body mass index [BMI]=
Weight (kg) / height 2 (M2)] in the range of 19.0 ~ 26.0 kg / m2 (including boundary value);
4) The skin in front of both thighs is normal and intact without damage;
5) The subjects must give informed consent to the study before the test and voluntarily sign a written informed consent form;
6) The subjects can communicate well with the researchers and complete the study according to 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）试验前 3 个月内参加过其他任何临床试验者；
2）对利多卡因、丙胺卡因等酰胺类局部麻醉药、本品中任何辅料或医用胶带过敏者，或对两种或两种以上药物（或食物）过敏者；
3）存在研究者判断为有临床意义的心血管（心律失常等）、肝脏、肾脏、内分泌、消化道、血液系统、呼吸系统、恶性肿瘤、精神异常、严重感染等病史或现有上述疾病者；
4）患有研究者判断为有临床意义的皮肤疾病（如：湿疹、荨麻疹、特异性皮炎等）者，或给药部位（双侧大腿前侧皮肤）有胎记、疤痕、纹身，开放性伤口者，或毛发旺盛者；
5）既往存在或现有葡萄糖-6-磷酸脱氢酶缺乏症、高铁血红蛋白血症者（问诊）；
6）有体位性低血压、晕针或晕血病史或静脉穿刺采血不耐受者；
7）试验前 4 周内接受过外科手术者，或者计划在研究期间进行手术者，且研究者判断会影响药物吸收、分布、代谢、排泄；
8）研究首次用药前 3 个月内献血或失血≥400 mL，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；
9）筛选前 4 周内使用过任何与利多卡因、丙胺卡因有相互作用的药物（如 III 类抗心律失常药（胺碘酮）、西咪替丁或 β 受体阻滞剂等）或与高铁血红蛋白诱导药物有关的药物（如磺酰胺、硝基呋喃妥因、苯妥英钠、苯巴比妥等）者，或筛选前 4 周内双侧大腿前侧皮肤使用了外用皮肤科药物治疗者；
10）筛选前 1 个月内接受过灭活疫苗接种，筛选前 3 个月内接受过活/减毒疫苗接种或计划在试验期间接受灭/活/减毒疫苗接种者；
11）试验前 14 天内使用过任何处方药（疫苗除外）、非处方药、中草药、保健品者；
12）试验前 3 个月内饮用过量（一天 8 杯以上，1 杯=200 mL）茶、咖啡或含咖啡因的饮料者；或研究首次用药前 48 h 内，摄入任何含有咖啡因的食物或饮料（如咖啡、浓茶、巧克力等）者；
13）试验前 3 个月平均每日吸烟量多于 5 支者，以及入选后至整个试验期间不能接受禁止吸烟者；
14）试验前 6 个月内经常饮酒者，即每周饮酒超过 14 单位酒精（1 单位=360 mL 啤酒或45 mL 酒精量为 40%的烈酒或 150 mL 葡萄酒）；或试验期间不愿意停止饮酒或任何含酒精的制品；
15）不能遵守统一饮食（如对标准餐食物不耐受等）者；
16）药物滥用者或试验前 3 个月使用过软毒品（如：大麻）或试验前 1 年服用硬毒品（如：可卡因、苯环己哌啶等）者；
17）妊娠或哺乳期妇女，以及男性或女性受试者（或其伴侣）在入选后至试验结束后 3 个月内不愿意或不能采取一种或一种以上有效避孕措施；
18）生命体征异常者（收缩压<90 mmHg 或>140 mmHg，舒张压<50 mmHg 或>90 mmHg；心率<50 bpm 或>100 bpm）或体格检查、心电图、实验室检查异常有临床意义（以临床研究医生判断为准）；
19）研究者认为存在任何可能影响受试者提供知情同意或遵循试验方案的情况，或受试者参加试验可能影响试验结果或自身安全。
每周期入住期排除标准：
除上述注明的入住期问诊项，符合下列条件之一也应排除：
1）自上次离院后至入住前有伴随用药、急性疾病且经研究者判断对试验结果有影响者；
2）自上次离院后至入住前服用烟草制品或服用过含有酒精的制品且经研究者判断对试验结果有影响者；
3）自上次离院后至入住前饮用茶、咖啡或含咖啡因的饮料且经研究者判断对试验结果有影响者；
4）自上次离院后至入住前发生非保护性行为者；
5）用药前 48 h 内，摄入过任何富含黄嘌呤或葡萄柚成份或其他影响药物吸收、分布、代谢、排泄等的饮料或食物者；
6）生命体征异常有临床意义且研究者认为无法再继续参加试验者；
7）药物滥用筛查（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）试验阳性者；
8）酒精呼气测试结果>0.0 mg/100 mL 者；
9）女性血妊娠检查异常且有临床意义者；
10）给药部位（双侧大腿前侧皮肤）有异常者；
11）受试者可能因为其他原因而不能完成本研究或经研究者判断具有其它不宜参加试验原因者。

Exclusion criteria：

Any one of the following conditions cannot be selected for this test:
1) Those who have participated in any other clinical trials within 3 months before the trial;
2) Those allergic to lidocaine, procaine and other amide local anesthetics, any excipients in this product or medical tape, or those allergic to two or more drugs (or food);
3) Those who have a history of cardiovascular (arrhythmia, etc.), liver, kidney, endocrine, digestive tract, blood system, respiratory system, malignant tumor, mental disorder, serious infection and other diseases of clinical significance judged by the researcher or have the above diseases;
4) Patients with clinically significant skin diseases (such as eczema, urticaria, specific dermatitis, etc.) judged by the researcher, or those with birthmarks, scars, tattoos, open wounds, or exuberant hair at the administration site (bilateral front thigh skin);
5) Patients with previous or existing glucose-6-phosphate dehydrogenase deficiency and methemoglobinemia (consultation);
6) Those who have a history of postural hypotension, needle syncope or blood syncope, or intolerance to venipuncture;
7) Those who have undergone surgery within 4 weeks before the trial, or those who plan to perform surgery during the study, and the investigator judges that it will affect drug absorption, distribution, metabolism and excretion;
8) Blood donation or blood loss ≥ 400 ml within 3 months before the first drug use in the study, or blood donation or blood components planned during the study or within 3 months after the end of the study;
9) Any drug (such as class III antiarrhythmic drugs (amiodarone), cimetidine or other drugs) that interact with lidocaine and prilocaine within 4 weeks before screening β Receptor blockers, etc.) or drugs related to methemoglobin inducing drugs (such as sulfonamide, nitrofurantoin, phenytoin sodium, phenobarbital, etc.), or those who used topical dermatological drugs for bilateral anterior thigh skin within 4 weeks before screening;
10) Those who have received inactivated vaccine within 1 month before screening, those who have received live / attenuated vaccine within 3 months before screening or plan to receive inactivated / attenuated vaccine during the trial;
11) Those who have used any prescription drugs (except vaccines), over-the-counter drugs, Chinese herbal medicines and health products within 14 days before the test;
12) Drinking too much (more than 8 cups a day, 1 cup = 200 ml) tea, coffee or caffeinated drinks within 3 months before the test; Or ingesting any food or beverage containing caffeine (such as coffee, strong tea, chocolate, etc.) within 48 hours before the first medication;
13) Those who smoked more than 5 cigarettes per day in the three months before the trial, and those who were not allowed to smoke during the whole trial period after enrollment;
14) Regular drinkers within 6 months before the test, i.e. drinking more than 14 units of alcohol per week (1 unit = 360 ml beer or 45 ml spirits with 40% alcohol or 150 ml wine); Or unwilling to stop drinking alcohol or any alcoholic products during the test;
15) Unable to follow the unified diet (such as intolerance to standard food);
16) Drug abusers or those who used soft drugs (such as marijuana) 3 months before the test or hard drugs (such as cocaine, phencyclohexylpiperidine, etc.) 1 year before the test;
17) Pregnant or lactating women, and male or female subjects (or their partners) are unwilling or unable to take one or more effective contraceptive measures from enrollment to 3 months after the end of the trial;
18) Abnormal vital signs (systolic blood pressure < 90 mmHg or > 140 mmHg, diastolic blood pressure < 50 mmHg or > 90 mmHg; heart rate < 50 BPM or > 100 BPM) or abnormal physical examination, ECG and laboratory examination with clinical significance (subject to the judgment of clinical research doctors);
19) The researcher believes that there is any situation that may affect the subjects to provide informed consent or follow the test protocol, or the subjects' participation in the test may affect the test results or their own safety.
Weekly check-in exclusion criteria:
In addition to the check-in consultation items indicated above, those meeting one of the following conditions shall also be excluded:
1) Patients who had concomitant medication and acute diseases from the last time they left the hospital to before admission, and who were judged by the investigator to have an impact on the test results;
2) Those who have taken tobacco products or alcohol containing products since the last time they left the hospital and before admission, and have been judged by the researcher to have an impact on the test results;
3) Those who drank tea, coffee or caffeinated drinks from the last time they left the hospital to before they checked in, and who were judged by the researcher to have an impact on the test results;
4) The occurrence of unprotected sexual behavior from the last time of leaving the hospital to before admission;
5) Ingesting any beverage or food rich in xanthine or grapefruit or other beverages or foods that affect the absorption, distribution, metabolism and excretion of drugs within 48 hours before medication;
6) Those whose vital signs are abnormal and have clinical significance and the investigator believes that they can no longer participate in the trial;
7) Drug abuse screening (morphine, methamphetamine, ketamine, dimethylbisoxyamphetamine, tetrahydrocannabinol acid) test positive;
8) Alcohol breath test results > 0.0 mg / 100 ml;
9) Women with abnormal blood pregnancy test and clinical significance;
10) Abnormal administration site (bilateral front thigh skin);
11) The subjects may not be able to complete the study for other reasons, or the researchers judge that they are not suitable to participate in the test for other reasons.

研究实施时间：

Study execute time：

从 From 2022-02-01 00:00:00至 To 2022-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-02-01 00:00:00 至 To 2022-12-31 00:00:00

干预措施：

Interventions：

组别：

T组

样本量：

 15

Group：

Group T

Sample size：

干预措施：

先给受试制剂再给参比试剂

干预措施代码：

Intervention：

Give the test preparation first and then the reference reagent

Intervention code：

组别：

R组

样本量：

 15

Group：

Group R

Sample size：

干预措施：

先给参比试剂再给受试制剂

干预措施代码：

Intervention：

Give the reference reagent first and then the test product

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

 长沙 

Country：

China

Province：

Hu'nan

City：

Changsha

单位(医院)：

 中南大学湘雅三医院 

单位级别：

 三级甲等 

Institution
hospital：

The Third Xiangya Hospital of Central South University

Level of the institution：

Tertiary 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：

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 60 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）：

本研究采用区组随机方法，组间比例 1:1，让每位受试者随机的的进入（T-R）组或（R-T）组。

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

In this study, the method of block randomization was adopted, and the ratio between groups was 1:1. Each subject was randomly entered into (T-R) group or (R-T) group.

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）：

否

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

NO

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：

本次试验数据管理采用电子数据采集系统（EDC），由浙江太美医疗科技股份有限公司提供电子数据采集系统（eCollect ? V5），具体内容详见“数据管理计划”。数据管理计划：由数据经理撰写，作为整个数据管理过程的指导性文件，数据管理所有过程均应按照计划进行操作。

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

Electronic Data Acquisition system (EDC) was used for data management in this study. ECollect ? V5 was provided by Zhejiang Taimei Medical Technology Co.LTD. Please refer to "Data Management Plan" for details. Data management plan: it is written by the data manager and serves as a guiding document for the entire data management process. All data management processes should follow the plan.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

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  2022-01-08 07:53:23