ChiCTR2000040405 版本V1.1 版本创建时间2021/02/22 01:36:53 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：

 ChiCTR2000040405 

最近更新日期：

Date of Last Refreshed on：

 2021-02-22 01:35:36 

注册时间：

Date of Registration：

 2020-11-28 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

TUL01101片在健康成人受试者中单次给药的安全性、耐受性、药代动力学和药效动力学特征的临床试验

Public title：

Clinical trials of the safety, tolerability, pharmacokinetics and pharmacodynamic characteristics of TUL01101 tablets in a single dose of healthy adult subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

TUL01101片在健康成人受试者中单次给药的安全性、耐受性、药代动力学和药效动力学特征的临床试验

Scientific title：

Clinical trials of the safety, tolerability, pharmacokinetics and pharmacodynamic characteristics of TUL01101 tablets in a single dose of healthy adult 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：

胡展晴 

研究负责人：

阳国平 

Applicant：

Hu Zhanqing 

Study leader：

Yang Guoping 

申请注册联系人电话：

Applicant telephone：

 +86 15607310928

研究负责人电话：

Study leader's
telephone：

0731-89918665

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：

 1390178553@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：

湖南省长沙市河西岳麓区桐梓坡路138号

研究负责人通讯地址：

湖南省长沙市河西岳麓区桐梓坡路138号

Applicant address：

138 Tongzipo Road, Hexiyuelu District, Changsha, Hunan, China

Study leader's address：

138 Tongzipo Road, Hexiyuelu District, Changsha, Hunan, 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：

中南大学湘雅三医院临床试验研究中心

Applicant's institution：

Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University

研究负责人所在单位：

中南大学湘雅三医院临床试验研究中心

Affiliation of the Leader：

Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University

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：

 20105

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医学伦理分委员会

Name of the ethic committee：

IRB, the Third Xiangya Hospital, Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

 2020-07-29 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：

中国湖南省长沙市中南大学湘雅三医院伦理委员会医学伦理分委员会

Contact Address of the ethic committee：

IRB, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha, Hu'nan, 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：

中南大学湘雅三医院临床试验研究中心

Primary sponsor：

Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University

研究实施负责（组长）单位地址：

中国湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

138 Tong-Zi-Po Road, Yuelu District, Changsha, Hu'nan, 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)：

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：

河西岳麓区桐梓坡路138号

Institution
hospital：

Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University

Address：

138 Tongzipo Road, Hexiyuelu District

经费或物资来源：

珠海联邦制药股份有限公司

Source(s) of funding：

Zhuhai United Laboratories Co., Ltd.

研究疾病：

中度至重度的活动性类风湿性关节炎  

Target disease：

Moderate to severe active rheumatoid arthritis

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：

主要目的：评估健康成人空腹条件下单次服用TUL01101后的安全性和耐受性。次要目的：评估健康成人空腹条件下单次服用TUL01101后的药代动力学特征及生物转化情况。评估健康成人空腹条件下单次服用TUL01101后的药效动力学特征。探索性目的：评估TUL01101对QT/QTc间期的影响；健康成人服用TUL01101后的物质平衡初步研究。  

Objectives of Study：

Main purpose: To evaluate the safety and tolerability of a single dose of TUL01101 in healthy adults under fasting conditions. Secondary objective: To evaluate the pharmacokinetic characteristics and biotransformation of TUL01101 after a single administration of TUL01101 under fasting conditions in healthy adults. To evaluate the pharmacodynamic characteristics of healthy adults after a single administration of TUL01101 under fasting conditions. Exploratory purpose: To evaluate the effect of TUL01101 on the QT/QTc interval; a preliminary study on the material balance of healthy adults after taking TUL01101.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

有资格参加本次研究的受试者必须符合下列各条入选标准：
1、健康志愿者年龄在18–45岁（包括18岁和45岁），性别不限，女性受试者（育龄女性）在月经后入组；
2、男性受试者体重≥50 kg，女性受试者≥45 kg，体重指数(BMI)在19–26kg/m2（包括两端界值）；
3、受试者（包括伴侣）愿意自筛选至试验用药品给药后6个月自愿采取适当有效避孕措施（非避孕药）等，试验用药品给药后6个月内无捐献精子、卵子计划；
4、对本研究已充分了解，自愿参加，已签署书面的知情同意书；
受试者能够和研究者进行良好的沟通，并且理解和遵守本研究的各项要求。

Inclusion criteria

Subjects eligible to participate in this study must meet the following selection criteria:
1. Healthy volunteers are 18-45 years old (including 18 years old and 45 years old), regardless of gender, female subjects (females of childbearing age) are enrolled in the group after menstruation;
2. Male subjects weigh ≥50 kg, female subjects ≥45 kg, and body mass index (BMI) is 19–26kg/m2 (including both ends);
3. Subjects (including partners) are willing to voluntarily take appropriate and effective contraceptive measures (non-contraceptives) from screening to 6 months after the administration of the test drug, and no sperm or egg donated within 6 months after the administration of the test drug plan;
4. Fully understand this study, volunteer to participate, and have signed a written informed consent form;
The subject can communicate well with the researcher, and understand and comply with the requirements of this research.

排除标准：

以下任何一条均可将受试者排除，不入选研究：
1、已知有临床意义的药物过敏史或特应性变态反应性疾病史（哮喘、荨麻疹、湿疹性皮炎）或已知对试验用药品或类似活性药物的药物过敏者；
2、既往有临床严重的或目前在临床上有明显或有临床意义的疾病/异常（包括但不限于神经系统、心血管系统、呼吸系统、血液和淋巴系统、免疫系统、肾脏、肝脏、胃肠道、代谢及骨骼等系统疾病及恶性肿瘤病史者、神经病学或精神病学疾病/异常）者；
3、近一年内频繁的感染病史（发作次数≥3次），给药前3个月内有过感染病史，如复发性口腔疱疹、生殖器疱疹、带状疱疹等复发性病毒感染史；
4、体格检查、生命体征、实验室检查、胸片结果异常有临床意义者；
5、筛选时血常规检查中白细胞计数、中性粒细胞计数及淋巴细胞计数低于正常值下限或高于正常值上限者，网织红细胞计数及血红蛋白低于正常值下限者；
6、筛选时乙型肝炎表面抗原或丙型肝炎抗体或梅毒抗体检测阳性者；或HIV抗体非阴性；
7、C反应蛋白（CRP）和血沉（ESR）检查结果高于正常值上限者；
8、筛选期血清肌酐水平估算的内生肌酐清除率低于80ml/min的受试者（内生肌酐清除率公式为Ccr=(140-年龄)×体重(kg)/[72×Scr(mg/dl) ]或Ccr=[(140-年龄)×体重(kg)]/[0.818×Scr(umol/L)] 。内生肌酐清楚率计算过程中应注意肌酐的单位，女性按计算结果×0.85）；
9、筛选时心电图检查QTcB > 450 ms者（Fridericia’s公式：QTcB = QT/（RR）1/3），或者心电图中其他经研究者判定为异常有临床意义者；
10、筛选前6个月内接受过任何手术者；
11、筛选前3个月内失血或献血超过400 mL，或接受过血液或血液成份输注者；
12、筛选前3个月内参加过任何药物或医疗器械的临床试验且给药者（含安慰剂组）；
13、筛选前6个月内接种过任何疫苗者；
14、在服用本研究用药前1个月内服用了任何药物，包括处方药、非处方药和草药；
15、既往有药物滥用史，或尿药筛查阳性者；
16、首次给药前3个月内每日吸烟超过5支香烟或等量烟草的或者试验期间不能戒烟者；
17、首次给药前28天内女性每周饮酒超过7杯或男性每周饮酒超过14杯（1杯=5盎司（150mL）葡萄酒=12盎司（360mL）啤酒=1.5盎司（45mL）烈酒），或首次给药前48小时内服用过任何含酒精的制品，或在筛选访视/基线访视时酒精呼气试验为阳性者；
18、首次给药前14天内饮用过量（一天8杯以上，1杯=200 mL）茶、咖啡或含咖啡因的饮料，或食用葡萄柚（西柚）、或富含黄嘌呤的食物或饮料者，或给药前48小时内及试验期间不能停止食用富含黄嘌呤成分的食物或饮料（如巧克力、茶、咖啡及可乐等）、或葡萄柚（西柚）或柚子以及含葡萄柚或柚子成分的产品（西柚汁、柚子汁等）者；
19、参加研究期间仍需或计划从事剧烈体力活动或运动者；
20、哺乳期女性”与“女性血HCG≥5 mIU/mL”者；
21、不能耐受静脉穿刺者，有晕针或晕血史者；
研究者认为不适合参加临床试验的其他情况。

Exclusion criteria：

Subjects can be excluded from any of the following items and not included in the study:
1. Known clinically significant drug allergy history or atopic allergic disease history (asthma, urticaria, eczema dermatitis) or known allergy to experimental drugs or drugs with similar active drugs;
2. Past clinically serious or current clinically significant or clinically significant diseases/abnormalities (including but not limited to nervous system, cardiovascular system, respiratory system, blood and lymphatic system, immune system, kidney, liver, stomach Those with a history of intestinal, metabolic and bone system diseases and malignant tumors, neurological or psychiatric diseases/abnormalities);
3. Frequent history of infections in the past year (number of attacks ≥ 3 times), history of infections within 3 months before administration, such as recurrent oral herpes, genital herpes, herpes zoster and other recurrent viral infections;
4. The abnormal results of physical examination, vital signs, laboratory examinations, and chest radiographs have clinical significance;
5. The white blood cell count, neutrophil count and lymphocyte count in the routine blood examination during screening are below the lower limit of normal value or higher than the upper limit of normal value, and the reticulocyte count and hemoglobin are lower than the lower limit of normal value;
6. Those who tested positive for hepatitis B surface antigen or hepatitis C antibody or syphilis antibody during screening; or HIV antibody was not negative;
7. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) test results are higher than the upper limit of normal;
8. Subjects whose endogenous creatinine clearance rate estimated by serum creatinine level during the screening period is less than 80ml/min (the endogenous creatinine clearance rate formula is Ccr=(140-age)×weight (kg)/[72×Scr(mg) /dl)] or Ccr=[(140-age)×weight (kg)]/[0.818×Scr(umol/L)]. The unit of creatinine should be paid attention to during the calculation of endogenous creatinine clear rate. For women, follow the calculation result× 0.85);
9. Those with QTcB> 450 ms during screening (Fridericia’s formula: QTcB = QT/(RR)1/3), or other abnormal ECGs judged by the investigator as having clinical significance;
10. Those who have undergone any surgery within 6 months before screening;
11. Those who have lost blood or donated more than 400 mL of blood within 3 months before screening, or have received blood or blood component transfusion;
12. Those who have participated in and administered any drug or medical device clinical trial within 3 months before screening (including the placebo group);
13. Those who have received any vaccine within 6 months before screening;
14. Any medications, including prescription drugs, over-the-counter drugs, and herbal medicines, were taken within 1 month before taking the drugs in this study;
15. Those who have a history of drug abuse or have a positive urine drug screening;
16. People who smoked more than 5 cigarettes or equivalent amount of tobacco a day within 3 months before the first administration or who could not quit smoking during the trial period;
17. In the 28 days before the first administration, women drink more than 7 glasses per week or men drink more than 14 glasses per week (1 cup = 5 ounces (150 mL) wine = 12 ounces (360 mL) beer = 1.5 ounces (45 mL) of spirits), Or those who have taken any alcohol-containing products within 48 hours before the first dose, or the alcohol breath test was positive during the screening visit/baseline visit;
18. Drinking excessive amounts of tea, coffee or caffeinated beverages within 14 days before the first administration (more than 8 cups a day, 1 cup = 200 mL), or eating grapefruit (grapefruit), or xanthine-rich food or beverages People, or within 48 hours before administration and during the trial period, can’t stop eating xanthine-rich foods or beverages (such as chocolate, tea, coffee and cola, etc.), or grapefruit (grapefruit) or grapefruit, and grapefruit or Products with grapefruit ingredients (grapefruit juice, grapefruit juice, etc.);
19. Those who still need or plan to engage in strenuous physical activities or sports during the study period;
20. Those who are "breastfeeding women" and "female blood HCG≥5 mIU/mL";
21. Those who cannot tolerate venipuncture, have a history of fainting needles or fainting blood;
The investigator believes that it is not suitable to participate in other situations of clinical trials.

研究实施时间：

Study execute time：

从 From 2020-11-26 00:00:00至 To 1990-01-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-11-26 00:00:00 至 To 1990-01-01 00:00:00

干预措施：

Interventions：

组别：

试验组

样本量：

 62

Group：

experimental group

Sample size：

干预措施：

单次给药剂量递增研究分为7个剂量组： 3 mg、6 mg、12 mg、20 mg、30 mg、40 mg、55 mg。3 mg剂量组（哨兵组）2例受试者，均接受试验药，男女各1例，其它每个剂量组10例受试者（随机分配TUL011018例，安慰剂2例），男女各半。

干预措施代码：

Intervention：

The single-dose dose escalation study is divided into 7 dose groups: 3 mg, 6 mg, 12 mg, 20 mg, 30 mg, 40 mg, 55 mg. Two subjects in the 3 mg dose group (sentinel group) received the test drug, one male and one female, and 10 subjects in each of the other dose groups (randomly ass

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临床试验研究中心 

单位级别：

 三级甲等 

Institution
hospital：

Center for Clinical Pharmacology, the Third Xiangya Hospital, 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：

指标中文名：

药代动力学参数

指标类型：

主要指标

Outcome：

Pharmacokinetic parameters

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

尿药浓度

指标类型：

主要指标

Outcome：

Urine 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：

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：

标本中文名：

粪便

组织：

Sample Name：

stool

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）：

采用分层区组随机化方法，按性别分层。由统计单位随机人员以SAS软件（9.4或以上版本）产生随机号以及随机号所对应治疗组别。每个剂量组生成一个随机表（盲底）密封，一式三份，密封后分别保存在临床单位、申办单位和生物检测单位（PK）。

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

Using stratified block randomization method, stratified by gender. Random personnel from the statistical unit use SAS software (version 9.4 or above) to generate random numbers and the treatment groups corresponding to the random numbers. Each dose group generates a random table (blind bottom), sealed in triplicate,

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

Blinding：

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

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）：

文章发表

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

Articles published

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：

本次试验采用电子化数据管理，使用DAS for EDC(V6.0)。数据管理计划（DMP）：DMP作为数据管理的指导性文件由数据管理员（DM）撰写，申办单位批准，数据管理工作将根据DMP定义的时间、内容及方法进行。

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

This experiment uses electronic data management, using DAS for EDC (V6.0). Data Management Plan (DMP): As a guiding document for data management, DMP is written by the data manager (DM) and approved by the sponsor. The data management will be carried out according to the time, content and method defined by DMP.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2020-11-28 10:32:28