ChiCTR2000038991 版本V1.3 版本创建时间2021/01/10 11:46:59 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：

 ChiCTR2000038991 

最近更新日期：

Date of Last Refreshed on：

 2021-01-07 14:51:10 

注册时间：

Date of Registration：

 2020-10-12 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

【辑】达可替尼片在健康受试者中的药代动力学研究

Public title：

Pharmacokinetic study of dacomitinib tablets in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

达可替尼片在健康受试者中的药代动力学研究

Scientific title：

Pharmacokinetic study of dacomitinib 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：

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：

 +86 18920606639

研究负责人电话：

Study leader's
telephone：

+86 15132966386

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：

邢台医专第二附属医院

Affiliation of the Leader：

The Second Affiliated Hospital of Xingtai Medical College

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-HIS-061

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：

邢台医专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：

 2020-09-15 00:00:00

伦理委员会联系人：

郑曦

Contact Name of the ethic committee：

Zheng Xi

伦理委员会联系地址：

河北省邢台市桥西区钢铁北路618号

Contact Address of the ethic committee：

618 Iron and Steel Road North, Qiaoxi 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：

河北省邢台市桥西区钢铁北路618号

Primary sponsor's address：

618 Iron and Steel Road North, Qiaoxi 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)：

四川

市(区县)：

成都

Country：

China

Province：

Sichuan

City：

Chengdu

单位(医院)：

成都倍特药业股份有限公司

具体地址：

高新区高朋大道15号

Institution
hospital：

Brilliant Pharmacutical Co., Ltd.Chengdu

Address：

15 Gaopeng Avenue, High-Tech Zone

经费或物资来源：

成都倍特药业股份有限公司

Source(s) of funding：

Brilliant pharmacutical co.,LTD.CHENGDU

研究疾病：

表皮生长因子受体（EGFR）19号外显子缺失突变或21号外显子L858R置换突变的局部晚期或转移性非小细胞肺癌（NSCLC）  

Target disease：

Epidermal growth factor receptor (EGFR) exon 19 deletion mutation or exon 21 L858R substitution mutation locally advanced or metastatic non-small cell lung cancer (NSCLC)

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：

主要研究目的：本研究以成都倍特药业股份有限公司生产的达可替尼片（45mg）为受试制剂，以Pfizer Europe MA EEIG公司生产的在欧盟上市的达可替尼片（45mg，商品名：Vizimpro）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药代动力学相似性。 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 purpose: In this study, dacomitinib tablets (45mg) produced by Chengdu Better Pharmaceutical Co., Ltd. were used as the test preparation, and dacomitinib tablets (45mg, 45mg, produced by Pfizer Europe MA EEIG) which were marketed in the EU Trade name: Vizimpro) is a reference preparation, to evaluate the pharmacokinetic similarity of the test preparation and the reference preparation when administered under fasting conditions. Secondary research purpose: to observe the safety of 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：

1）性别：男性和女性健康受试者，且入选的受试者应有适当的性别比例；
2）年龄：18~45周岁（含括临界值）的健康受试者；
3）体重：男性受试者不应低于50.0kg，女性受试者不应低于45.0kg，身体质量指数【BMI=体重（kg）/身高2（m2）】在19.0～26.0kg/m2范围内（含括临界值）；
4）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；
5）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

1. Gender: male and female healthy subjects, and the selected subjects should have appropriate gender ratio;
2. Age: 18-45 years old (including critical value) healthy subjects;
3. Weight: male subjects should not be less than 50.0kg, female subjects should not be less than 45.0kg, body mass index [BMI = weight (kg) / height 2 (M2)] in the range of 19.0-26.0kg/m2 (including the critical value);
4. The subjects must give informed consent to the study before the trial and sign the written informed consent voluntarily;
5. The subjects can communicate well with the researchers and complete the research 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）对达可替尼片及其相关化合物和辅料中任何成份过敏者，或对两种或两种以上药物（或食物）过敏者；
2）不能遵守统一饮食（如对标准餐食物不耐受等）者；
3）不能耐受静脉穿刺者，有晕针晕血史者；
4）存在研究者判断为有临床意义的皮肤、心血管、肝脏、肾脏、内分泌、消化系统、血液系统、呼吸系统、感染、恶性肿瘤、精神系统、神经系统等重大病史或现有上述疾病者；
5）在筛选前6个月内接受过重大外科手术者，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（阑尾炎手术除外）；
6）筛选期体格检查、生命体征测量、心电图检查、胸部CT检查、实验室检查（血常规、尿常规、血生化、凝血功能等），研究者判断异常有临床意义者；
7）筛选期体格检查发现有鼻粘膜异常或结膜炎或口腔黏膜炎或甲沟炎者；
8）乙肝表面抗原、丙肝抗体、梅毒螺旋体抗体或艾滋病病毒抗体检查结果异常有临床意义者；
9）既往长期（筛选前3个月内）饮用过量（一天8杯以上，1杯=200mL）茶、咖啡或含咖啡因的饮料者；或入组前48小时内，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；
10）入组前48小时内，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；
11）筛选前4周内使用过任何与达可替尼片有相互作用的药物（如质子泵抑制剂雷贝拉唑、CYP2D6底物右美沙芬等）；
12）试验前6个月内使用过长效雌激素或孕激素注射剂或埋植片者；试验前30天内使用过短效避孕药者；
13）筛选前14天内使用过任何处方药、非处方药、中草药、保健品者；
14）筛选前3个月每日吸烟量多于5支者，或入组前烟碱检查（尿液尼古丁检测）阳性者，或入选后至整个试验期间不能接受禁止吸烟者；
15）研究首次用药前酒精呼气检测结果阳性（大于0.0mg/100ml），或筛选前6个月内每周饮酒超过14个标准单位(1标准单位含14g酒精，如360mL啤酒或45mL酒精量为40%的烈酒或150mL葡萄酒)；
16）试验前1年内有药物滥用史（如吗啡、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、可卡因等）或研究首次用药前药筛检查阳性者；
17）妊娠或哺乳期妇女，以及在整个试验期间及研究结束后3个月内有妊娠计划或有捐精捐卵计划的男性受试者（或其伴侣）或女性受试者；
18）研究首次用药前3个月内参加了其他临床试验且服用了研究药物者；
19）研究首次用药前3个月内献血或失血≥450mL，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；
20）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。

Exclusion criteria：

Those who have one of the following conditions can not be included in this test:
1. Subjects allergic to any component of dacotinib tablets and its related compounds and excipients, or persons allergic to two or more drugs (or food); 2;
2. Those who can't follow the same diet (such as intolerance to standard food, etc.);
3. Those who can't tolerate venipuncture and have a history of needle and blood sickness;
4. Patients with clinically significant skin, cardiovascular, liver, kidney, endocrine, digestive system, blood system, respiratory system, infection, malignant tumor, mental system, nervous system and other major medical history or existing above diseases judged by researchers;
5. Patients who had undergone major surgery within 6 months before screening, or planned to undergo surgery during the study period, and those who had undergone surgery that would affect drug absorption, distribution, metabolism and excretion (except appendicitis surgery);
6. Physical examination, vital signs measurement, ECG examination, chest CT examination, laboratory examination (blood routine, urine routine, blood biochemistry, coagulation function, etc.) in screening period, and patients with abnormal clinical significance judged by researchers;
7. Patients with abnormal nasal mucosa or conjunctivitis or oral mucositis or paronychia found in screening physical examination;
8. Patients with abnormal results of hepatitis B surface antigen, hepatitis C antibody, Treponema pallidum antibody or HIV antibody with clinical significance;
9. Patients who had consumed too much tea, coffee or caffeinated drinks (more than 8 cups per day, 1 cup = 200ml) for a long time (within 3 months before screening); or those who had consumed any caffeinated food or drink (such as coffee, strong tea, chocolate, etc.) within 48 hours before enrollment;
10. Patients who have taken any drink or food rich in xanthine or grapefruit or other factors affecting drug absorption, distribution, metabolism and excretion within 48 hours before entering the group;
11. Patients who have used any drug that interacts with dacotinib tablets in the first 4 weeks of screening (such as rabeprazole, CYP2D6 substrate dextromethorphan, etc.);
12. Patients who used long-acting estrogen or progesterone injection or implant within 6 months before the trial; patients who used short acting contraceptives within 30 days before the trial; patients who used long-acting estrogen or progesterone injection or implant within 6 months before the trial;
13. Patients who have used any prescription drugs, over-the-counter drugs, Chinese herbal medicines and health care products within 14 days before screening;
14. The patients who smoked more than 5 cigarettes per day in the first 3 months, or who had positive nicotine test (urine nicotine test) before enrollment, or who could not accept no smoking during the whole trial period after enrollment;
15. Study the patients with positive results of alcohol breath test before the first medication (more than 0.0mg/100ml), or drink more than 14 standard units per week within 6 months before screening (1 standard unit contains 14g alcohol, such as 360ml beer or 45ml spirits with 40% alcohol or 150ml wine);
16. Patients with a history of drug abuse (such as morphine, methamphetamine, ketamine, dimethylene dioxoamphetamine, tetrahydrocannabinolic acid, cocaine, etc.) within one year before the trial or those with positive drug screening before the first drug use in the study;
17. Pregnant or lactating women, as well as male subjects (or their partners) or female subjects with pregnancy plans or sperm and egg donation plans during the whole trial period and within 3 months after the end of the study;
Patients who participated in the clinical trial for the first time within 18 months before taking the drug;
19. The subjects who donated blood or lost more than 450ml within 3 months before the first medication, or planned to donate blood or blood components during the study period or within 3 months after the end of the study;
20. The researchers believe that there are any circumstances that may affect the informed consent or compliance of the subjects, or the subjects' participation in the trial may affect the trial results or their own safety.

研究实施时间：

Study execute time：

从 From 2020-10-10 00:00:00至 To 2021-07-19 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-11-02 00:00:00 至 To 2021-07-19 00:00:00

干预措施：

Interventions：

组别：

A组

样本量：

 7

Group：

A group

Sample size：

干预措施：

TR

干预措施代码：

Intervention：

TR

Intervention code：

组别：

B组

样本量：

 7

Group：

B group

Sample size：

干预措施：

RT

干预措施代码：

Intervention：

RT

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 A

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：

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：

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：

从零到无穷大时间内血药浓度-时间曲线下面积

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：

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）：

随机表使用SAS 9.3（或以上版本）统计学软件、Microsoft Excel 或SPSS产生，根据受试者的随机号进行随机分组，在研究中的每名受试者接受受试制剂或参比制剂的顺序（A组、B组）将由随机表确定。

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

The random table was generated using SAS 9.3 (or above) statistical software, Microsoft Excel or SPSS, and randomized according to the random number of the subjects. In the study, the order in which each subject received the test or reference preparation ( Group A, Group B) will be determined by the

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

是Yes

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：

原始病历的所有数据必须核对，保证无误后签字并注明日期。监查员审核每份原始研究记录表，确认临床试验数据记录及时、准确、规范、完整。

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

All data in the original medical record must be checked, signed and dated after ensuring that it is correct. The inspector reviews each original research record sheet to confirm that the clinical trial data record is timely, accurate, standardized and complete.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2020-10-12 23:53:32