ChiCTR2200064910 版本V1.2 版本创建时间2023/05/08 00:54:54 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：

 ChiCTR2200064910 

最近更新日期：

Date of Last Refreshed on：

 2023-04-23 23:00:41 

注册时间：

Date of Registration：

 2022-10-21 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

HRG2101 吸入剂在健康成人中单、多次给药的安全性、耐受性及药代动力学研究

Public title：

Safety, tolerability and pharmacokinetics of HRG2101 inhaler in single and multiple doses in healthy adults

注册题目简写：

English Acronym：

研究课题的正式科学名称：

HRG2101 吸入剂在健康成人中单、多次给药的安全性、耐受性及药代动力学研究

Scientific title：

Safety, tolerability and pharmacokinetics of HRG2101 inhaler in single and multiple doses in healthy adults

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：

张美琳 

研究负责人：

阳国平 

Applicant：

Meilin Zhang 

Study leader：

Guooing Yang 

申请注册联系人电话：

Applicant telephone：

 +86 18723596158

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：

 zhangmeilin69@163.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 Tongzibo Road, Yuelu District, Changsha, Hunan

Study leader's address：

138 Tongzibo Road, Yuelu District, Changsha, Hunan

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 of Central South University

研究负责人所在单位：

中南大学湘雅三医院

Affiliation of the Leader：

The Third Xiangya Hospital of 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：

 22100

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：

Ethics Committee of the Third Xiangya Hospital of Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-08-24 00:00:00

伦理委员会联系人：

王晓敏

Contact Name of the ethic committee：

Xiaomin Wang

伦理委员会联系地址：

湖南省长沙市岳麓区桐梓坡路138号

Contact Address of the ethic committee：

138 Tongzipo Road, Yuelu District, Changsha, Hunan, 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 of 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 Tongzipo Road, Yuelu District, Changsha, Hunan, 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：

Hunan

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：

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

Address：

138 Tongzipo Road, Yuelu District

经费或物资来源：

江苏恒瑞医药股份有限公司

Source(s) of funding：

Jiangsu Hengrui Pharmaceutical Co., Ltd.

研究疾病：

特发性肺纤维化  

Target disease：

Idiopathic pulmonary fibrosis

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：

随机交叉对照 

Study design：

Cross-over 

研究目的：

1. 考察健康受试者经口吸入 HRG2101 后的安全性、耐受性及药代动力学特征。 2. 考察吸入流速对 HRG2101 的生物利用度的影响。 3. 考察健康受试者经口吸入 HRG2101 后的胃肠道和肺部吸收比例。 4. 考察健康受试者多次经口吸入 HRG2101 后的体内蓄积情况。 5. 比较 HRG2101 吸入剂与吡非尼酮片的相对生物利用度。  

Objectives of Study：

1. To investigate the safety, tolerance and pharmacokinetic characteristics of HRG2101 after oral inhalation in healthy subjects. 2. To investigate the effect of inhalation flow rate on the bioavailability of HRG2101. 3. Investigate the gastrointestinal tract and lung absorption ratio of healthy subjects after oral inhalation of HRG2101. 4. Investigate the accumulation of HRG2101 in healthy subjects after repeated oral inhalation. 5. To compare the relative bioavailability of HRG2101 inhalation and pirfenidone tablets.

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. 年龄≥18 周岁，男女均可；
2. 男性受试者体重≥50.0 kg，女性受试者体重≥45.0 kg，体重指数(BMI=体重(kg)/身高2 (m 2 ))在 19.0~26.0 kg/m 2 范围内(包括边界值)；
3. 有生育能力的女性受试者必须在首次用药前 7 天内及入住当天进行血清妊娠检查，且结果均为阴性。有生育能力的女性受试者和伴侣为育龄妇女的男性受试者必须同意从签署知情同意书开始直到安全性随访期结束遵守避孕要求（详见附件中的“避孕方式”）；
4. 受试者能够与研究者进行良好的沟通，经培训能正确的使用粉雾剂装置，能够按照研究者的要求完成研究；
5. 受试者充分了解试验目的、性质、方法以及可能发生的不良反应并自愿签署书面的知情同意书，并能够依照方案规定完成试验。

Inclusion criteria

1. Age >= 18 years old, both male and female;
2. The weight of male subjects is >= 50.0 kg, the weight of female subjects is >= 45.0 kg, and the body mass index (BMI = weight (kg)/height 2 (m2)) is within the range of 19.0-26.0 kg/m2 (including the boundary value) ;
3. Fertile female subjects must undergo a serum pregnancy test within 7 days before the first medication and on the day of check-in, and the results are all negative. Fertile female subjects and male subjects whose partners are women of childbearing age must agree to abide by the contraceptive requirements from the signing of the informed consent until the end of the safety follow-up period (see Contraceptive methods in the appendix for details);
4. The subject can communicate well with the researcher, can use the powder aerosol device correctly after training, and can complete the research according to the researcher's requirements;
5. The subject fully understands the purpose, nature, method and possible adverse reactions of the test and voluntarily signs a written informed consent, and can complete the test in accordance with the protocol.

排除标准：

1. 既往或目前患有循环系统、内分泌系统、神经系统、消化系统、呼吸系统、血液学、免疫学、精神病学及代谢异常等任何临床严重疾病，经研究者判定可能影响试验用药品药动学特征或安全性评价者；
2. 有光过敏史者，现有皮疹、瘙痒、红斑、湿疹等皮肤异常症状者；
3. 现有食欲不振、胃部不适、恶心、腹泻、胸口有灼烧感、消化不良等消化系统疾病或者嗜睡、晕眩、行走不稳感等精神神经系统疾病者；
4. 目前患有口腔疾病者（如口咽部念珠菌感染、口腔溃疡、口腔粘膜破损等）；
5. 筛选前 3 个月内接受过重大手术者，或既往接受了可能显著影响试验用药品药动学特征或安全性评价的手术者，或计划在研究期间进行手术者；
6. 已知对试验用药品、试验用药品类似物及辅料过敏或不耐受者，或有特定变态反应疾病者(如过敏性哮喘、荨麻疹、湿疹等)，或过敏体质者 (如对两种或以上药物、食物或花粉过敏)；
7. 试验前 1 个月内使用过任何抑制或诱导肝脏对药物代谢的药物(如：诱导剂—巴比妥类、卡马西平、苯妥英、糖皮质激素、奥美拉唑；抑制剂—SSRI 类抗抑郁药、西咪替丁、地尔硫卓、大环内酯类、硝基咪唑类、镇静催眠药、维拉帕米、氟喹诺酮类、抗组胺类)者；
8. 受试者在试验前 14 天内使用过任何药物(包括处方药、非处方药、维生素补充剂或中草药)、保健品或疫苗者；
9. 受试者在试验前 3 个月内服用过其他临床研究药物或使用试验器械者，或计划在本研究期间参加其他临床试验者；
10. 受试者在试验前 3 个月内献血或大量失血≥400 mL (女性生理性失血除外)、接受输血或使用血制品者，或计划在试验期间或试验结束后 1 个月内献血者；
11. 哺乳期女性；
12. 试验前 3 个月每天饮用过量茶、咖啡、西柚汁、含咖啡因的饮料(平均每天 8 杯以上，每杯200 mL)者；
13. 首次给药前 48 小时内服用过特殊饮食(如西柚、西柚汁或含西柚汁的食物/饮料、巧克力、烟草、酒精类、含咖啡因类等食物或饮料)者；
14. 受试者在试验前 6个月内有酒精滥用史，即平均每周饮酒超过 14个单位的酒精(1 单位=360mL 啤酒或 45 mL 酒精量为 40%的烈酒或 150 mL 葡萄酒) ，或试验期间不能停止饮酒者；
15. 受试者酒精呼气结果为阳性者；
16. 受试者在试验前 3 个月内平均每日吸烟量多于 5 支者，或试验期间不能戒烟者，或烟检检查结果为阳性者；
17. 受试者在试验前 6 个月内有药物滥用史或药物滥用筛查结果为阳性者；
18. 受试者乙肝病毒表面抗原、丙型肝炎病毒抗体、人类免疫缺陷病毒抗体、梅毒螺旋体抗体检查有一项或一项以上呈阳性者；
19. 筛选期各项检查(包括生命体征、体格检查、心电图、实验室检查、胸片、腹部 B 超)结果经临床医生判定为异常有临床意义者；
20. 肺功能检查：FEV1 实测值/FEV1 预计值≤80%或 FVC≤预计值的 80%；
21. 肝功能指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、γ-谷氨酰转肽酶(γ-GTP)、乳酸脱氢酶(LDH)超出正常值范围上限；
22. 对饮食有特殊要求，不能遵守统一饮食者；
23. 静脉采血困难或不能耐受静脉穿刺者；
24. 有晕针或晕血史者；
25. 其他原因研究者认为不应纳入者。

Exclusion criteria：

1. Previously or currently suffering from any clinically serious diseases such as circulatory system, endocrine system, nervous system, digestive system, respiratory system, hematology, immunology, psychiatry and metabolic abnormalities, which may affect the pharmacokinetics of the experimental drug as determined by the investigator medical characteristics or safety evaluators;
2. Those with a history of photosensitivity, those with skin abnormalities such as rash, itching, erythema, and eczema;
3. People with digestive system diseases such as loss of appetite, stomach discomfort, nausea, diarrhea, burning sensation in the chest, indigestion, or mental and nervous system diseases such as drowsiness, dizziness, and unsteady walking;
4. Currently suffering from oral diseases (such as oropharyngeal candida infection, oral ulcers, oral mucosal damage, etc.);
5. Those who have undergone major surgery within 3 months before screening, or those who have previously received surgery that may significantly affect the pharmacokinetic characteristics or safety evaluation of the investigational drug, or those who plan to undergo surgery during the study;
6. Those who are known to be allergic or intolerant to the test drug, test drug analogs and excipients, or have specific allergic diseases (such as allergic asthma, urticaria, eczema, etc.), or those with allergic constitution (such as to two or more drug, food or pollen allergies);
7. Any drug that inhibits or induces liver drug metabolism has been used within 1 month before the test (such as: inducers - barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines);
8. Subjects who have used any drugs (including prescription drugs, over-the-counter drugs, vitamin supplements or Chinese herbal medicines), health products or vaccines within 14 days before the test;
9. Subjects who have taken other clinical research drugs or used experimental devices within 3 months before the trial, or plan to participate in other clinical trials during this study;
10. Subjects who donated blood or lost a large amount of blood >= 400 mL (except for female physiological blood loss), received blood transfusion or used blood products within 3 months before the test, or planned to donate blood during the test or within 1 month after the end of the test;
11. Lactating women;
12. Those who drank excessive amounts of tea, coffee, grapefruit juice, and caffeinated beverages (more than 8 cups per day on average, 200 mL per cup) in the first 3 months of the test;
13. Those who have taken special diet (such as grapefruit, grapefruit juice or food/drink containing grapefruit juice, chocolate, tobacco, alcohol, caffeine and other food or drink) within 48 hours before the first administration;
14. The subject has a history of alcohol abuse within 6 months before the test, that is, the average weekly drinking of more than 14 units of alcohol (1 unit = 360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine), or Those who cannot stop drinking during the test;
15. Subjects whose alcohol breath results are positive;
16. Subjects who smoked more than 5 cigarettes per day on average within 3 months before the test, or who could not quit smoking during the test, or who had a positive smoke test result;
17. The subject has a history of drug abuse or a positive drug abuse screening result within 6 months before the test;
18. One or more of the subjects tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, and Treponema pallidum antibody;
19. The results of various examinations during the screening period (including vital signs, physical examination, electrocardiogram, laboratory examination, chest X-ray, and abdominal B-ultrasound) are judged by clinicians to be abnormal and have clinical significance;
20. Pulmonary function test: FEV1 measured value/FEV1 predicted value <= 80% or FVC <= 80% of predicted value;
21. Liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), γ-glutamyl transpeptidase (γ-GTP), lactate Hydrogenase (LDH) exceeds the upper limit of the normal range;
22. Those who have special requirements for diet and cannot follow a unified diet;
23. Those who have difficulty in venous blood collection or who cannot tolerate venipuncture;
24. Those who have a history of needle fainting or haemorrhage;
25. Other reasons that researchers think should not be included.

研究实施时间：

Study execute time：

从 From 2022-10-21 00:00:00至 To 1990-01-01 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2022-10-21 00:00:00 至 To 1990-01-01 00:00:00

干预措施：

Interventions：

组别：

1组

样本量：

 12

Group：

Group 1

Sample size：

干预措施：

采用两周期、自身交叉设计，受试者根据给药随机结果，分别采用峰流速为 30L/min 或 60L/min 的吸气方式单次经口吸入 25 mg HRG2101 吸入剂，第二周期交叉吸气方式，周期间清洗期 为 2 天。

干预措施代码：

Intervention：

Using a two-cycle, self-crossover design, subjects used peak flow rates of 30 L/min or respectively according to the random results of dosing 60 L/min inhalation mode single oral inhalation of 25 mg HRG2101 inhaler, second cycle cross-aspiration mode, weekly cleaning period for 2 days.

Intervention code：

组别：

2组

样本量：

 12

Group：

Group 2

Sample size：

干预措施：

采用两周期、自身交叉设计，受试者根据给药随机结果，分别采用活性炭阻断和未阻断 两种给药方式单次经口吸入 50 mg HRG2101 吸入剂，第二周期交叉给药方式，周期间清洗期为 2 天。

干预措施代码：

Intervention：

A two-period, self-crossover design was adopted. According to the random results of administration, the subjects inhaled 50 mg of HRG2101 inhalation by oral administration in two ways of activated charcoal blocking and non-blocking respectively. The cleaning period is 2 days.

Intervention code：

组别：

3组

样本量：

 12

Group：

Group 3

Sample size：

干预措施：

分为单次给药和多次给药两个阶段。单次给药阶段，受试者单次经口吸入 100 mg HRG2101 吸入剂，完成 PK 血样采集后直接进入多次给药阶段，而后连续给药 5 天，每天给药三次（tid）， 每次吸入 100 mg HRG2101 吸入剂。

干预措施代码：

Intervention：

Divided into two stages of single administration and multiple administration. In the single-dose phase, the subjects inhaled 100 mg HRG2101 inhalation orally once, and entered the multiple-dose phase directly after completing the PK blood sample collection, and then administered continuously for 5 days, three times a&#

Intervention code：

组别：

4组

样本量：

 12

Group：

Group 4

Sample size：

干预措施：

采用两周期、自身交叉设计，受试者根据给药随机结果，分别单次经口吸入 200 mg HRG2101 吸入剂或口服 200 mg 吡非尼酮片，第二周期交叉给药，周期间清洗期为 2 天。

干预措施代码：

Intervention：

Using a two-cycle, self-crossover design, subjects inhaled 200 mg orally in a single pass based on random dosing results HRG2101 inhalation or oral 200 mg pirfenidone tablets with a second cycle of cross-dosing and a 2-day cleansing period during the week.

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：

Hunan

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：

血浆浓度

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：

体格检查

指标类型：

主要指标

Outcome：

physical examination

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生命体征

指标类型：

主要指标

Outcome：

vital signs

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

实验室检查

指标类型：

主要指标

Outcome：

laboratory test

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

12导联心电图

指标类型：

主要指标

Outcome：

12-lead electrocardiogram

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件

指标类型：

主要指标

Outcome：

adverse event

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：

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 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）：

采用区组随机方法，让每位受试者按随机序列接受给药。该随机数据具有重现性，所设定的随机数初值种子参数需要保存。

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

Using block random method, let each subject receive administration in a random sequence. The random data is reproducible, and the set random number initial value seed parameter needs to be saved.

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）：

文章发表

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

Article 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，使用电子数据采集系统（DAS for EDC V6.0或以上版本）。电子病例报告表（eCRF）：数据管理员根据试验方案设计构建，并根据数据核查计划（DVP）设置逻辑核查，通过测试并获申办方批准后发布使用。 数据录入：eCRF数据来源于原始记录，由数据录入人员根据eCRF填写说明，将志愿者访视数据及时录入 EDC。

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

This experiment adopts electronic data management and uses electronic data acquisition system (DAS for EDC V6.0 or above). Electronic case report form (eCRF): The data administrator builds according to the design of the trial protocol, and sets up logical verification according to the data verification plan (DVP), which is released for use after passing the test and being approved by the sponsor. Data entry: The eCRF data comes from the original records, and the data entry personnel fill in the instructions according to the eCRF,and enter the volunteer visit data into the EDC in time.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2022-10-21 17:29:58