ChiCTR2300068484 版本V1.1 版本创建时间2023/05/19 14:53:06 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：

ChiCTR2300068484 

最近更新日期：

Date of Last Refreshed on：

2023-02-21 10:47:05 

注册时间：

Date of Registration：

2023-02-21 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

利多卡因凝胶贴膏在健康受试者外用条件下的单中心、随机、开放、单剂量、两周期、两序列、双交叉生物等效性试验

Public title：

Single center, randomized, open, single dose, two cycle, two sequence, double crossover bioequivalence test of lidocaine gel plaster for external use in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

利多卡因凝胶贴膏在健康受试者外用条件下的单中心、随机、开放、单剂量、两周期、两序列、双交叉生物等效性试验

Scientific title：

Single center, randomized, open, single dose, two cycle, two sequence, double crossover bioequivalence test of lidocaine gel plaster for external use 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：

王红丹 

研究负责人：

何小爱 

Applicant：

Wang hongdan 

Study leader：

He xiaoai 

申请注册联系人电话：

Applicant telephone：

0898-66803585

研究负责人电话：

Study leader's telephone：

0898-66828612

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：

wanghongdan0614@126.com

研究负责人电子邮件：

Study leader's E-mail：

xiaoaiziyu@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：

海南海口市龙华区金牛路17号

研究负责人通讯地址：

海口市海甸岛人民大道43号

Applicant address：

No. 17, Jinniu Road, Longhua District, Haikou, Hainan

Study leader's address：

No. 43, Renmin Avenue, Haidian Island, Haikou

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：

海南回元堂药业有限公司

Applicant's institution：

Hainan Huiyuantang Pharmaceutical Co., Ltd

研究负责人所在单位：

海口市人民医院

Affiliation of the Leader：

Haikou People's 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：

2022-(伦审)-153

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：

海口市人民医院生物医学伦理委员会

Name of the ethic committee：

Biomedical Ethics Committee of Haikou People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

2022-07-22 00:00:00

伦理委员会联系人：

邱英麒

Contact Name of the ethic committee：

Qiu yingqi

伦理委员会联系地址：

海口市人民大道43号

Contact Address of the ethic committee：

No. 43, Renmin Avenue, Haikou

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：

海口市人民医院

Primary sponsor：

Haikou People's Hospital

研究实施负责（组长）单位地址：

海口市海甸岛人民大道43号

Primary sponsor's address：

No. 43, Renmin Avenue, Haidian Island, Haikou

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

海南海口

市(区县)：

Country：

China

Province：

Hainan Haikou

City：

单位(医院)：

海南回元堂药业有限公司

具体地址：

海南海口市龙华区金牛路17号

Institution
hospital：

Hainan Huiyuantang Pharmaceutical Co., Ltd

Address：

No. 17, Jinniu Road, Longhua District, Haikou, Hainan

经费或物资来源：

申办者

Source(s) of funding：

the sponsor

Target disease：

Postherpetic neuralgia

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：以利多卡因的体内药代动力学参数（Cmax与AUC）为生物等效性的评价指标，在中国健康受试者外用条件下评估受试制剂（海南回元堂药业有限公司生产的利多卡因凝胶贴膏，规格5%）和参比制剂（Teikoku Seiyaku Co., Ltd.生产的利多卡因凝胶贴膏，规格5%，商品名：Lidoderm?）的生物等效性；以利多卡因的平均黏附力得分为非劣效的评价指标，在中国健康受试者外用条件下评估受试制剂和参比制剂的非劣效性。 次要目的：观察中国健康受试者外用条件下受试制剂和参比制剂的皮肤刺激性和安全性。  

Objectives of Study：

Main objective: to evaluate the test preparation (lidocaine gel plaster produced by Hainan Huiyuantang Pharmaceutical Co., Ltd., specification 5%) and the reference preparation (lidocaine gel plaster produced by Teikoku Seiyaku Co., Ltd., specification 5%) under the external use conditions of Chinese healthy subjects with the in vivo pharmacokinetic parameters (Cmax and AUC) of lidocaine as the evaluation index of bioequivalence ?） Bioequivalence; The average adhesion score of lidocaine was used as the non inferiority evaluation index to evaluate the non inferiority of the test preparation and reference preparation under the external use conditions of Chinese healthy subjects. Secondary objective: to observe the skin irritation and safety of the test preparation and reference preparation under external application conditions of Chinese 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)受试者必须在试验前对本试验知情同意、并对试验内容、过程及可能出现的不良反应充分了解，且自愿签署了书面的知情同意书；
2)受试者能够与研究者进行良好的沟通并能够依照方案规定完成试验；
3)性别：中国男性或女性；
4)年龄：≥18周岁；
5)体重指数范围为18.6~28.5 kg/m2【体重指数=体重/身高（kg/m2）】（包括边界值），男性体重不低于50kg（包括50kg），女性体重不低于45kg（包括45kg）。

Inclusion criteria

1) Before the test, the subject must have informed consent to the test, fully understand the test content, process and possible adverse reactions, and voluntarily signed a written informed consent form;
2) The subject can communicate well with the researcher and complete the test according to the protocol;
3) Gender: Chinese male or female;
4) Age: ≥ 18 years old;
5) The body mass index range is 18.6~28.5 kg/m2 [body mass index=weight/height 2 (kg/m2)] (including the boundary value). The weight of men is not less than 50 kg (including 50 kg), and that of women is not less than 45 kg (including 45 kg).

排除标准：

1)过敏体质：对两种或以上物质过敏者（粉尘、花粉、食物、药物等）；曾对肥皂、乳液、润肤膏、软膏、乳膏、化妆品、黏着剂或乳胶产生重大过敏反应者；对日光敏感的皮肤类型者；或对利多卡因、四卡因或酰胺类或酯类麻醉剂有过敏或变态反应史或者贴剂中所含成份过敏者；或对医疗胶带、胶黏剂敷料或其他皮肤贴剂过敏者；
2)现伴有显示有临床意义的下列疾病者（包括但不限于呼吸系统、循环系统、消化系统、血液系统、内分泌系统、免疫系统、皮肤系统、精神神经系统、五官科等相关疾病）；
3)患有任何增加出血性风险的疾病者，如急性胃炎或活动性溃疡伴出血、具有临床意义的血小板减少或贫血，以及有活动性病理性出血或有颅内出血病史者；
4)筛查前3个月内接受过重大手术，或计划在试验期间进行手术者，或接受过会影响药物吸收、分布、代谢、排泄的手术者；
5)各项生命体征、体格检查、心电图检查和实验室检查（血生化、血常规、尿常规、凝血功能）结果显示异常有临床意义者；
6)有乙肝、丙肝、艾滋病、梅毒病史和/或传染病四项检查中一项或一项以上异常有临床意义者；
7)首次给药前3个月内失血（女性生理性失血除外）或献血大于200mL者，和/或2周内献血小板者；
8)首次给药前7天内使用任何非处方药、中草药或保健品；或在首次给药前14天内使用任何处方药者；
9)首次给药前28天内使用过影响肝药酶的药物（如苯巴比妥、苯妥英、利福平、格鲁米特、灰黄霉素、西咪替丁、酮康唑、氯霉素、异烟肼等）；
10)筛查前1个月内接种过疫苗，或计划在试验期间接种者；
11)首次给药前3个月内使用了任何临床试验药物者；
12)尿药筛查阳性或在过去有药物滥用史或筛选前三个月内使用过毒品者；
13)筛选前3个月内平均每日吸烟量多于5支者或不同意给药前48h及住院期间避免使用任何烟草类产品者；
14)筛选前6个月内经常饮酒者，即每周饮酒超过14个单位的酒精（1单位=360mL酒精含量为5%的啤酒或45mL酒精含量为40%的烈酒或150mL酒精含量为12%的葡萄酒），或不同意给药前48h及住院期间停止酒精摄入，或呼气酒精测试阳性者；
15)筛选前3个月内每天饮用过量茶、咖啡和/或含咖啡因的饮料者（8杯以上，1杯=250mL）或不同意给药前48h及住院期间禁止摄入茶、咖啡和/或含咖啡因的食物、葡萄柚（西柚）和/或葡萄柚汁（西柚汁），和/或含罂粟的产品者；
16)背部敷贴部位皮肤为油性、刚刚剃过或者有损伤（切伤或者剃伤）或者发炎（发红或者皮疹）的者；未治愈的皮肤疾病或病症如特应性皮炎，牛皮癣，白癜风的病史或已知改变皮肤外观或生理反应（例如糖尿病，卟啉症）的病症；皮肤癌症史（如黑色素瘤，鳞状细胞癌），除了浅表性的不涉及用药部位的基底细胞癌；
17)两背部之间的皮肤颜色明显不同者；用药部位影响药物黏贴或皮肤评价或可能影响药物吸收者（如毛发过多、伤疤、纹身、皮肤颜色异常等）；用药部位有开放性溃疡者；
18)签署知情同意书开始3个月内有生育计划（包括捐精、捐卵）和/或不同意采取有效避孕方法（试验期间非药物）者；
19)受试者可能因为其他原因而不能完成本研究或研究者认为不应纳入者。
女性受试者除上述要求外，符合下列条件的也应排除：
20)妊娠期或哺乳期妇女或妊娠检查结果阳性者；
21)首次给药前30天内使用过口服避孕药者；
22)首次给药前6个月内使用过长效雌激素和/或孕激素注射剂和/或埋植片者；
23)育龄女性首次给药前14天内与伴侣发生非保护性性行为者。

Exclusion criteria：

1) Allergic constitution: people who are allergic to two or more substances (dust, pollen, food, drugs, etc.); Have had a major allergic reaction to soap, lotion, skin cream, ointment, cream, cosmetics, adhesives or latex; Skin type sensitive to sunlight; Or has a history of allergy or allergic reaction to lidocaine, tetracaine or amide or ester anesthetics or the ingredients contained in the patch; Or allergic to medical tape, adhesive dressing or other skin patches;

2) People with the following diseases with clinical significance (including but not limited to respiratory system, circulatory system, digestive system, blood system, endocrine system, immune system, skin system, nervous system, ENT and other related diseases);

3) Patients with any disease that increases the risk of bleeding, such as acute gastritis or active ulcer with bleeding, clinically significant thrombocytopenia or anemia, and patients with active pathological bleeding or history of intracranial hemorrhage;

4) Those who have undergone major surgery within 3 months before screening, or who plan to undergo surgery during the trial, or who have undergone surgery that will affect drug absorption, distribution, metabolism and excretion;

5) The results of various vital signs, physical examination, ECG examination and laboratory examination (blood biochemistry, blood routine, urine routine, blood coagulation function) show abnormalities with clinical significance;

6) Those who have one or more abnormalities of hepatitis B, hepatitis C, AIDS, syphilis and/or infectious diseases with clinical significance;

7) Blood loss (except female physiological blood loss) or blood donation greater than 200mL within 3 months before the first administration, and/or platelet donation within 2 weeks;

8) Use any over-the-counter medicine, Chinese herbal medicine or health care products within 7 days before the first administration; Or use any prescription drug within 14 days before the first administration;

9) Drugs that affect liver drug enzymes (such as phenobarbital, phenytoin, rifampicin, glumide, griseofulvin, cimetidine, ketoconazole, chloramphenicol, isoniazid, etc.) were used within 28 days before the first administration;

10) Those who have been vaccinated within 1 month before the screening or plan to vaccinate during the trial;

11) Those who have used any clinical trial drug within 3 months before the first administration;

12) Those who are positive in urine drug screening or have used drugs in the past or within three months before screening;

13) Those who smoke more than 5 cigarettes per day on average within 3 months before screening or those who do not agree to avoid using any tobacco products 48 hours before administration and during hospitalization;

14) Those who regularly drink alcohol within 6 months before screening, i.e., those who drink more than 14 units of alcohol every week (1 unit=360 mL of beer with 5% alcohol content, 45 mL of spirits with 40% alcohol content, or 150 mL of wine with 12% alcohol content), or do not agree to stop drinking alcohol 48 hours before administration and during hospitalization, or those who have positive breath alcohol test;

15) Those who drink too much tea, coffee and/or caffeinated drinks every day within 3 months before screening (more than 8 cups, 1 cup=250mL) or those who do not agree to take tea, coffee and/or caffeinated food, grapefruit (grapefruit) and/or grapefruit juice (grapefruit juice) 48 hours before administration and during hospitalization, and/or products containing opium poppy;

16) The skin on the back application site is oily, freshly shaved or damaged (cut or shaved) or inflamed (red or rash); Untreated skin diseases or diseases such as atopic dermatitis, psoriasis, vitiligo, or diseases known to change skin appearance or physiological reaction (such as diabetes, porphyria); History of skin cancer (such as melanoma, squamous cell carcinoma), except for superficial basal cell carcinoma that does not involve the drug site;

17) The skin color between the two backs is obviously different; Those whose application site affects drug adhesion or skin evaluation or may affect drug absorption (such as excessive hair, scar, tattoo, abnormal skin color, etc.); Open ulcer at the application site;

18) Those who have family planning (including sperm donation and egg donation) and/or do not agree to take effective contraceptive methods (non drugs during the trial) within 3 months after signing the informed consent form;

19) Subjects may not be able to complete the study due to other reasons or should not be included in the study.In addition to the above requirements, female subjects meeting the following conditions shall also be excluded:

20) Pregnant or lactating women or women with positive pregnancy test results;
21) Those who have used oral contraceptives within 30 days before the first administration;

22) Those who have used long-acting estrogen and/or progesterone injections and/or implants within 6 months before the first administration;

23) Women of childbearing age have unprotected sex with their partners within 14 days before the first administration.

研究实施时间：

Study execute time：

从 From 2022-06-23 00:00:00至 To 2022-11-21 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2022-07-27 00:00:00 至 To 2022-08-07 00:00:00  

干预措施：

Interventions：

组别：

RT组

样本量：

15

Group：

RT group

Sample size：

干预措施：

第一周期用参比制剂，第二周期用受试制剂

干预措施代码：

Intervention：

The reference preparation is used for the first period, and the test preparation is used for the second period

Intervention code：

组别：

TR组

样本量：

15

Group：

TR group

Sample size：

干预措施：

受试者第一周期用受试制剂，第二周期用参比制剂

干预措施代码：

Intervention：

Subjects use the test preparation in the first cycle and the reference preparation 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)：

 海南 

市(区县)：

 海口 

Country：

China 

Province：

Hainan 

City：

Haikou 

单位(医院)：

海口市人民医院 

单位级别：

三甲 

Institution
hospital：

Haikou People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

主要药代动力学评价指标：血浆中利多卡因的Cmax、AUC0-t、AUC0-∞等；

指标类型：

主要指标

Outcome：

Main pharmacokinetic evaluation indexes: Cmax, AUC0-t, AUC0 - ∞, etc. of lidocaine in plasma;

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

血浆中利多卡因的Tmax、t1/2、λz；

指标类型：

次要指标

Outcome：

Lidocaine in plasma Tmax、t1/2、 λ z

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性评价指标：不良事件、严重不良事件、生命体征、体格检查、实验室检查、心电图

指标类型：

副作用指标

Outcome：

Safety evaluation indicators: adverse events, serious adverse events, vital signs, physical examination, laboratory examination, electrocardiogram

Type：

Adverse events

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

黏附力评价指标：根据FDA提出的评分系统进行分级评分； 皮肤刺激性评价指标：根据FDA提出的评分系统进行分级评分。

指标类型：

附加指标

Outcome：

Adhesion evaluation index: graded according to the scoring system proposed by FDA; Skin irritation evaluation index: graded according to the scoring system proposed by FDA.

Type：

Additional 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 43 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）：

由统计师按照随机表应用SAS（9.4或更高版本）按区组随机产生。

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

The statisticians shall apply SAS (version 9.4 or higher) according to the randomization table to generate randomly by block.

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

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）：

临床试验公共管理平台 http://www.medresman.org.cn

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

Clinical Trial Management Public Platform http://www.medresman.org.cn

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：

本研究数据管理采用电子化数据管理系统EDC

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

The data management of this study adopts the electronic data management system EDC

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2023-02-21 10:46:56