ChiCTR2400090209 版本V1.0 版本创建时间2024/09/25 17:40:37 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：

ChiCTR2400090209 

最近更新日期：

Date of Last Refreshed on：

2024-09-25 17:39:54 

注册时间：

Date of Registration：

2024-09-25 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

丁丙诺啡透皮贴剂人体生物等效性试验和黏附力试验

Public title：

Bioequivalence and adhesion tests of Buprenorphine Transdermal Patches in humans

注册题目简写：

English Acronym：

研究课题的正式科学名称：

丁丙诺啡透皮贴剂人体生物等效性试验和黏附力试验

Scientific title：

Bioequivalence and adhesion tests of Buprenorphine Transdermal Patches in humans

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：

毛妙付 

研究负责人：

谢志红 

Applicant：

Miaofu Mao 

Study leader：

Zhihong Xie 

申请注册联系人电话：

Applicant telephone：

+86 717 6346240

研究负责人电话：

Study leader's telephone：

+86 20 3415 3599

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：

maomiaofu@renfu.com.cn

研究负责人电子邮件：

Study leader's E-mail：

xzh0302@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：

武汉宜昌市东林路 519 号

研究负责人通讯地址：

广州市海珠区昌岗东路250号

Applicant address：

519 Donglin Road, Yichang City, Wuhan

Study leader's address：

250 Changgang East Road, Haizhu District, Guangzhou

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：

宜昌人福药业有限责任公司

Applicant's institution：

Yichang Humanwell Pharmaceutical Co.,Ltd.

研究负责人所在单位：

广州医科大学附属第二医院

Affiliation of the Leader：

Second Affiliated Hospital of Guangzhou Medical University

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：

Y2024-43-01

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：

广州医科大学附属第二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 Guangzhou Medical University

伦理委员会批准日期：

Date of approved by ethic committee：

2024-08-09 00:00:00

伦理委员会联系人：

杜潇潇

Contact Name of the ethic committee：

Xiaoxiao Du

伦理委员会联系地址：

广州市海珠区昌岗东路250号

Contact Address of the ethic committee：

250 Changgang East Road, Haizhu District, Guangzhou

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 20 34153599

伦理委员会联系人邮箱：

Contact email of the ethic committee：

gyeyec@163.com

研究实施负责（组长）单位：

广州医科大学附属第二医院

Primary sponsor：

Second Affiliated Hospital of Guangzhou Medical University

研究实施负责（组长）单位地址：

广州市海珠区昌岗东路250号

Primary sponsor's address：

250 Changgang East Road, Haizhu District, Guangzhou

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

广东

市(区县)：

Country：

China

Province：

Guangdong

City：

单位(医院)：

广州医科大学附属第二医院

具体地址：

广州市海珠区昌岗东路250号

Institution
hospital：

Second Affiliated Hospital of Guangzhou Medical University

Address：

250 Changgang East Road, Haizhu District, Guangzhou

经费或物资来源：

宜昌人福药业有限责任公司

Source(s) of funding：

Yichang Humanwell Pharmaceutical Co.,Ltd.

Target disease：

Chronic pain not controlled by non-opioid analgesics

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 上市后药物 

Study phase：

4

研究设计：

随机交叉对照 

Study design：

Cross-over 

研究目的：

研究中国健康受试者空腹条件下单剂量使用受试制剂丁丙诺啡透皮贴剂与参比制剂丁丙诺啡透皮贴剂后的体内药代动力学特征，评价两种制剂的生物等效性。  

Objectives of Study：

To study the in vivo pharmacokinetics of a single dose of transdermal buprenorphine patch in healthy Chinese subjects under fasting conditions, and to evaluate the bioequivalence of the two formulations.

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.试验前签署知情同意书、并对试验内容、过程及可能出现的不良反应充分了解，自 愿参加且能够按照试验方案要求完成研究；
2.受试者（包括男性受试者）自筛选前 14 天内禁欲或已采取了有效避孕措施且筛选 期至试验用药品最后一次给药后 6 个月内无生育计划，保证筛选前 14 天至最后一 次试验药品给药后 1 个月的性生活中采用一种或一种以上非药物避孕措施；
3.年龄为 18～55 周岁男性和女性受试者（包括 18 和 55 周岁）；
4.男性受试者体重≥50.0kg，女性受试者体重≥45.0kg，体重指数（BMI）＝体重 （kg）/身高 2（m 2），体重指数在 19.0～26.0 范围内（包括临界值）；
5.用药部位皮肤必须健康、清洁、干燥、非毛发浓密，没有红肿、刺激、烧伤或割 伤。

Inclusion criteria

1.Informed consent was signed before the trial, and the patients fully understood the content, process and possible adverse reactions of the trial. They were willing to participate in the study and were able to complete the study in accordance with the requirements of the trial protocol.
2.Subjects (including male subjects) were abstinential or had taken effective contraceptive measures within 14 days before screening and had no childbearing plan within 6 months after the last dose of investigational drug. They were guaranteed to use one or more non-drug contraceptive measures during sexual life from 14 days before screening to 1 month after the last dose of investigational drug.
3.Male and female subjects aged 18-55 years old (including 18 and 55 years old);
4.Body weight of male subjects ≥50.0kg, female subjects ≥45.0kg, body mass index (BMI) = weight (kg)/height 2 (m 2), BMI in the range of 19.0 to 26.0 (including critical value);
5.The skin at the site of application must be healthy, clean, dry, non-hairy, and free of redness, irritation, burns, or cuts.

排除标准：

1.已知对试验用药品（包括伴随用药盐酸纳曲酮）的任何组分或类似药物有过敏史 者，或为过敏体质者，有过敏性皮疹者；
2.既往或目前患有循环系统、内分泌系统、神经系统、呼吸系统（如慢性阻塞性肺 病、哮喘和呼吸睡眠暂停综合征）、消化系统、泌尿及生殖系统、免疫系统、血液 学、精神病学、皮肤病学等任何临床的严重疾病或慢性疾病，经研究者判断可能干 扰试验结果者；
3.在贴敷部位有显著的颜色差异、过度的毛发、瘢痕组织、纹身、开放的伤口、近期 的晒伤或影响贴敷部位皮肤评估以及经皮给药（TDS）效应的穿刺；
4.患有皮肤疾病如特应性皮炎、牛皮癣、白癜风或已知改变皮肤外观或生理反应的疾 病者（例如糖尿病、卟啉症等）；
5.存在胃肠道、肝脏或肾脏疾病，或任何已知干扰药物吸收、分布、代谢或排泄的情 况；
6.既往无明显诱因频发恶心、呕吐者；
7.有癫痫史或有症状的头部外伤；
8.有直立性低血压病史或症状者；或在筛选访视时从卧位改为直立位后 3 分钟内收缩 压（SBP）下降≥20mmHg 或舒张压（DBP）下降≥10mmHg；
9.心电图检查男性 QTc≥450 ms，女性 QTc≥470 ms，或伴有其他具有临床意义的 ECG 异常；
10.筛选前 3 个月内接受过手术或者或计划在试验期间进行外科手术，及凡接受过会影 响药物吸收、分布、代谢、排泄的手术者；
11.乙肝表面抗原、丙型肝炎病毒抗体、人类免疫缺陷病毒抗体或梅毒螺旋体抗体任一 检测结果阳性者；
12.筛选前 3 个月平均每周饮用大于 14 个单位的酒精：1 单位=360mL 啤酒或 45mL 酒 精量为 40%的烈酒或 150mL 葡萄酒，或在试验期间不能停止服用任何含酒精的制 品，或筛选期酒精筛查阳性者；
13.入住前 2 天内进食可能影响药物体内代谢的饮食（包括葡萄柚或含葡萄柚成分的产 品、或含巧克力、或富含嘌呤的食物等），或研究者认为有其他影响药物吸收、分 布、代谢、排泄的饮食者，或不同意试验期间停止进食上述饮食者；
14.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 =250mL）者；或不同意试验期间停止饮用茶、咖啡和/或含咖啡因的饮料者；
15.筛选前 3 个月内曾参加其他临床试验且使用了试验用药品者；
16.有晕针或晕血史者，且研究者判断有临床意义；
17.女性受试者在筛选前 30 天内使用过口服避孕药，或筛选前 6 个月内使用过长效雌 激素或孕激素注射剂或埋植片，或在筛选期或临床试验中正处在哺乳期或妊娠期 者；
18.筛选前 14 天内服用过任何处方药、任何非处方药、中草药或保健品者；
19.筛选前五年内有药物滥用史或筛选前 3 个月使用过软毒品（如：大麻）或筛选前 1年内服用过硬毒品（如：可卡因、苯环己哌啶等）者，或基线期尿液药物筛查阳性者；
20.筛选前 1 个月内接种过疫苗者或试验期间计划接种疫苗者；
21.筛选前 3 个月内献血或大量失血（>400mL）或计划在试验期间献血者；
22.筛选前 3 个月内平均每日吸烟量多于 5 支者，或试验期间不能停止使用任何烟草类 产品者；
23.经研究医生判断有临床意义的异常情况，包括体格检查、生命体征监测、心电图或临床实验室检查；
24.职业运动员；
25.其它研究者判定不适宜参加的受试者。

Exclusion criteria：

1.He had a known history of allergy to any component of the investigational product (including concomitant naltrexone hydrochloride) or similar drugs Or those with allergic constitution or allergic rash;
2.Previous or current circulatory, endocrine, nervous, or respiratory disease (e.g., chronic obstructive pulmonary disease) Diseases, asthma and apnea syndrome), digestive system, urinary and reproductive system, immune system, blood "Any clinically serious disease or chronic disease, such as medical, psychiatric, dermatological, etc. that may be caused by the investigator's judgment. Disturbing test results;
3.There are significant color differences at the site of application, excessive hair, scar tissue, tattoos, open wounds, recent Sunburn or puncture affecting the skin of the application site and the effect of transdermal drug delivery (TDS);
4.A skin condition such as atopic dermatitis, psoriasis, vitiligo, or a condition known to alter the appearance or physiological response of the skin. Disease (e.g. diabetes, porphyria, etc.);
5.The presence of gastrointestinal, hepatic, or renal disease, or any condition known to interfere with the absorption, distribution, metabolism, or excretion of the drug. Condition;
6.Recurrent nausea and vomiting without obvious inducement in the past;
7.A history of epilepsy or symptomatic head trauma;
8.Patients with a history or symptoms of orthostatic hypotension; Or contraction within 3 min after changing from supine to upright position at the screening visit Decreases in blood pressure (SBP) of ≥20mmHg or diastolic blood pressure (DBP) of ≥10mmHg;
9.QTc≥450 ms in men and ≥470 ms in women, or with other clinically significant ECG Abnormal ECG;
10.Patients who had undergone surgery within 3 months before screening or were planning to undergo surgery during the trial, and any patients who had undergone imaging The operation of drug absorption, distribution, metabolism and excretion;
11.Any antibody to hepatitis B surface antigen, hepatitis C virus, human immunodeficiency virus, or treponema pallidum Those with positive test results;
12.Average consumption of more than 14 units of alcohol per week during the 3 months before screening: 1 unit =360 ml of beer or 45mL of liquor Spirits or 150mL wine of 40% precision, or inability to stop taking any alcoholic beverage during the trial Alcohol intake, or alcohol screening positive during the screening period;
13.Any diet (including grapefruit or products containing grapefruit) that may affect drug metabolism within 2 days before admission Or containing chocolate, or foods rich in purine, etc.), or researchers believe that there are other factors affecting drug absorption Diet, metabolism, excretion diet, or did not agree to stop eating the above diet during the trial;
14.Consuming excessive amounts of tea, coffee, and/or caffeine-rich beverages (> 8 cups, 1 cup per day) in the 3 months before screening =250mL); Or who did not agree to stop drinking tea, coffee, and/or caffeinated beverages during the trial;
15.Those who had participated in other clinical trials and used investigational drugs within 3 months before screening;
16.Patients with a history of fainting or bleeding, and the investigator judged that it was clinically significant;
17.Women who had used oral contraceptives within 30 days before screening, or had used long-acting estrogen or progestin injections or implants within 6 months before screening, or were lactating or pregnant at the time of screening or the trial;
18.Who had taken any prescription medication, any over-the-counter medication, herbal medicine or health supplement within 14 days before screening;
19.Subjects with drug abuse history within 5 years or soft drugs (such as cannabis) use within 3 months before screening or hard drugs (such as cocaine, phenzyhexidine) use within 1 year before screening, or with positive urine drug screening results at baseline;
20.Persons who were vaccinated within 1 month before screening or planned to be vaccinated during the trial;
21.Those who had donated blood within 3 months before screening or had a large amount of blood loss (>400mL) or planned to donate blood during the trial;
22.If they smoked an average of more than 5 cigarettes per day in the 3 months before screening, or were unable to stop using any tobacco products during the trial;
23.Abnormalities judged by the study physician to be clinically significant, including physical examination, monitoring of vital signs, electrocardiography, or clinical laboratory testing;
24.professional athlete；
25.Other subjects judged by the investigator to be ineligible for participation.

研究实施时间：

Study execute time：

从 From 2024-09-26 00:00:00至 To 2024-11-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-09-26 00:00:00 至 To 2024-10-12 00:00:00  

干预措施：

Interventions：

组别：

R-T

样本量：

20

Group：

R-T

Sample size：

干预措施：

第一周期丁丙诺啡透皮贴剂（R）；第二周期丁丙诺啡透皮贴剂（T）

干预措施代码：

Intervention：

Phase 1 Buprenorphine Transdermal Patches（R）；Phase 2 Buprenorphine Transdermal Patches（T）

Intervention code：

组别：

T-R

样本量：

20

Group：

T-R

Sample size：

干预措施：

第一周期丁丙诺啡透皮贴剂（T）；第二周期丁丙诺啡透皮贴剂（R）

干预措施代码：

Intervention：

Phase 1 Buprenorphine Transdermal Patches（T）；Phase 2 Buprenorphine Transdermal Patches（R）

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 广东 

市(区县)：

  

Country：

China 

Province：

Guangdong 

City：

 

单位(医院)：

广州医科大学附属第二医院 

单位级别：

三级甲等 

Institution
hospital：

Second Affiliated Hospital of Guangzhou Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性指标

指标类型：

次要指标

Outcome：

Safety indexes

Type：

Secondary indicator

测量时间点：

整个试验过程中

测量方法：

生命体征监测、体格检查、实验室检查（血生化、血常规、尿常规、凝血功能）、12导联心电图和用药部位皮肤反应等检查

Measure time point of outcome：

Throughout the trial

Measure method：

vital signs monitoring, physical examination, laboratory tests (blood biochemistry, blood routine, urine routine, coagulation function), 12-lead electrocardiogram and skin reaction at the medication site were examined

指标中文名：

Cmax，

指标类型：

主要指标

Outcome：

Cmax，

Type：

Primary indicator

测量时间点：

给药后0h-264h

测量方法：

根据丁丙诺啡的血药浓度数据，通过非房室模型估算药代动力学参数，估算的药代动力学参数。

Measure time point of outcome：

0h-264h after administration

Measure method：

According to the plasma concentration data of buprenorphine, the pharmacokinetic parameters were estimated by non-compartmental model.

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：

给药后0h-264h

测量方法：

根据丁丙诺啡的血药浓度数据，通过非房室模型估算药代动力学参数，估算的药代动力学参数。

Measure time point of outcome：

0h-264h after administration

Measure method：

According to the plasma concentration data of buprenorphine, the pharmacokinetic parameters were estimated by non-compartmental model.

指标中文名：

AUC0-∞

指标类型：

主要指标

Outcome：

AUC0-∞

Type：

Primary indicator

测量时间点：

给药后0h-264h

测量方法：

根据丁丙诺啡的血药浓度数据，通过非房室模型估算药代动力学参数，估算的药代动力学参数。

Measure time point of outcome：

0h-264h after administration

Measure method：

According to the plasma concentration data of buprenorphine, the pharmacokinetic parameters were estimated by non-compartmental model.

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：

尿样

组织：

Sample Name：

urine sample

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 55 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）：

本研究采用本试验采用区组随机方法，组间比例 1:1，将受试者随机分配到 TR 和 RT 组。

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

In this study, subjects were randomly assigned to TR and RT groups using a block randomization method with a 1:1 ratio between groups.

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

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）：

无

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

none

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：

数据录入EDC系统

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

All required data will be recorded in EDC.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-09-25 17:39:54