ChiCTR2000032638 版本V1.3 版本创建时间2020/05/05 01:16:18 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：

 ChiCTR2000032638 

最近更新日期：

Date of Last Refreshed on：

 2020-05-05 01:13:50 

注册时间：

Date of Registration：

 2020-05-04 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

刘献芳医师：请尽快上传伦理审批文件。 单次肌肉注射培门冬酶注射液与 Oncaspar在中国健康成年男性受试者中的药代动力学及相对生物利用度研究（2）

Public title：

Pharmacokinetics and relative bioavailability of single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male subjects (2)

注册题目简写：

English Acronym：

研究课题的正式科学名称：

单次肌肉注射培门冬酶注射液与 Oncaspar在中国健康成年男性受试者中的药代动力学及相对生物利用度研究（2）

Scientific title：

Pharmacokinetics and relative bioavailability of single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male subjects (2)

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 Gangtie Road North, Qiaoxi District, Xingtai, Hebei, China

Study leader's address：

618 Gangtie 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-HS-054

伦理委员会批件附件：

Approved file of Ethical Committee：

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：

 2020-04-26 00:00:00

伦理委员会联系人：

郑曦

Contact Name of the ethic committee：

Zhen 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 Gangtie 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 Hosptial 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 Gangtie 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)：

北京

市(区县)：

Country：

China

Province：

Beijing

City：

单位(医院)：

北京双鹭药业股份有限公司

具体地址：

海淀区阜石路 69 号碧桐园 1 号 楼

Institution
hospital：

Beijing Shuanglu Pharmaceutical Co., Ltd.

Address：

Building 1, Bitongyuan, 69 Fushi Road, Haidian District

经费或物资来源：

北京双鹭药业股份有限公司

Source(s) of funding：

Beijing Shuanglu Pharmaceutical Co., Ltd.

研究疾病：

从出生到18岁儿童和成人急性淋巴细胞白血病患者治疗。  

Target disease：

Treatment for children and adults with acute lymphoblastic leukemia from birth to 18 years of age.

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：

随机平行对照 

Study design：

Parallel 

研究目的：

主要研究目的： 1.评估单次肌肉注射培门冬酶注射液与Oncaspar在中国健康成年男性受试者中的安全性和耐受性，并为正式试验剂量选择提供依据。 2.评估单次肌肉注射培门冬酶注射液与Oncaspar在中国健康成年男性受试者中的相对生物利用度。 次要研究目的： 1.评估单次肌肉注射培门冬酶注射液与Oncaspar在中国健康成年男性受试者中的药效动力学（PD）特征。 2.评估单次肌肉注射培门冬酶注射液与Oncaspar在中国健康成年男性受试者中的免疫原性。  

Objectives of Study：

Primary objectives: 1.Evaluate the safety and tolerability of single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male subjects. 2.Evaluate the relative bioavailability of single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male subjects. Secondary objectives: 1.Evaluate the pharmacodynamic (PD) characteristics of single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male subjects. 2.Evaluate the immunogenicity of a single intramuscular injection of asparaginase injection and Oncaspar in Chinese healthy adult male 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研究知情同意，自愿签署书面的知情同意书，并能够按照方案要求完成研究。
2.性别：中国健康成年男性受试者。
3.筛选时年龄：18~45周岁的男性健康志愿者（包括边界值）。
4.筛选时受试者体重≥50.0kg。体重指数在19.0~26.0 kg/m2范围内（含边界值），体重指数（BMI）=体重(kg)/身高2（m2）。
5.筛选时体表面积（BSA）在1.6-2.0m2范围男性健康志愿者（包括临界值）。体表面积（BSA）计算公式：中国成年男性BSA=0.00607×身高+0.0127×体重-0.0698（注：身高单位为cm，体重单位为kg）。
6.筛选时实验室检查项目中：谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素、淀粉酶必须在正常值范围内；其他实验室检查项目、体格检查、生命体征检测、胸部CT检查和心电图检查经研究者判断为正常或异常无临床意义者。
7.受试者能够和研究者进行良好的沟通，并且理解和遵守本项研究的各项要求。

Inclusion criteria

1. Subjects who have to give informed consent to the study before the trial, sign a written informed consent voluntarily, and can complete the study according to the requirements of the scheme;
2. Gender: Chinese healthy adult male subjects.
3. Age at screening: male healthy volunteers aged 18-45 years(including boundary value).
4. Subjects with weight >= 50.0kg at the time of screening. Body mass index is in the range of 19.0-26.0 kg / m2 (including boundary value), body mass index = weight (kg) / height 2 (M2).
5. The body surface area (BSA) of male healthy volunteers ranged from 1.6 to 2.0m2 (including the threshold value). Body surface area (BSA) calculation formula: Chinese adult male BSA = 0.00607 x height + 0.0127 x weight -0.0698 (Note: height unit is cm, weight unit is kg).
6. Laboratory examination items during screening: ast, alt, total bilirubin and amylase must be within the normal range; other laboratory examination items, physical examination, vital signs examination, chest CT examination and ECG examination are normal or abnormal subjects without clinical significance judged by researchers.
7. Subjects who can communicate well with researchers and understand and comply with the requirements of this study.

排除标准：

1.试验前3个月内入组其他临床试验并服用相应的试验药物，或正在参加其他临床试验者。
2.筛选前14天有武汉市及周边地区，或其他有病例报告社区的旅行史或居住史者；筛选前14天有与新型冠状病毒感染者的接触史者；筛选前14天有与来自武汉及周边地区，或来自有病例报告社区的发热或有呼吸道症状患者的接触史者。
3.筛选期乙肝表面抗原、丙肝抗体、梅毒螺旋体抗体或人体免疫缺陷病毒抗体检查结果异常有临床意义者。
4.存在研究者判断为有临床意义的心血管、肝脏、肾脏、消化道、皮肤、内分泌、血液系统、呼吸系统、神经系统（如癫痫等）、感染、恶性肿瘤及其他病史（如中耳炎病史或中耳炎患者、出现过急性血栓症、有胰腺炎病史、有明显出血史）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（阑尾炎和疝修补手术除外）。
6.筛选前28天内接受过疫苗接种者。
7.试验前酒精呼气测试结果大于0.0mg/100mL者，或筛选前3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)，以及入选后至整个试验期间不能接受禁酒者。
8.筛选前3个月每日吸烟量多于5支者，或使用烟草制品、尼古丁制品（贴剂、口香糖等）；以及入选后至整个试验期间不能接受禁止吸烟者。
9.对培门冬酶或左旋门冬酰胺酶及其相关化合物和辅料中任何成份有过敏史者，或对两种或两种以上药物（或食物）过敏者。
10.试验前药物滥用及毒品检测阳性或试验前5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）者。
11.试验前3个月内献血或失血≥400mL，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。
12.受试者（或其伴侣）在试验期间至试验结束后3个月内不愿意或不能采取一种或一种以上避孕措施；或受试者在试验期间和试验结束后3个月内为女性供精计划者。
13.试验前28天内使用过任何处方药、非处方药、中草药、保健品者。
14.首次给药前48小时内，摄入过任何富含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。
15.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；或研究首次用药前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。
16.不能遵守统一饮食（如对标准餐食物不耐受等）者。
17.不能耐受静脉穿刺者，有晕针晕血史者。
18.首次服用研究药物前14天内在饮食或运动习惯上有重大变化者（如节食、暴饮暴食或无运动习惯者突然剧烈运动等）。
19.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者。

Exclusion criteria：

1. Those who are enrolled in other clinical trials and take the corresponding test drugs within 3 months before the trial, or who are participating in other clinical trials;
2. People who have travel or residence history in Wuhan city and surrounding areas, or other communities with case reports 14 days before screening; those who have contact history with new coronavirus infection 14 days before screening; People in Wuhan and surrounding areas, or those with a history of fever or respiratory symptoms from a community with a case report;
3. Hepatitis B surface antigen, hepatitis C antibody, Treponema pallidum antibody or human immunodeficiency virus antibody test results of screening period are abnormal clinical significance;
4. There are cardiovascular, liver, kidney, digestive tract, skin, endocrine, blood system, respiratory system, nervous system (such as epilepsy, etc.), infection, malignant tumor, and other medical history (such as history of otitis media) that the researchers judge to have clinical significance Or patients with otitis media, acute thrombosis, a history of pancreatitis, and a history of significant bleeding) or those with existing diseases;
5. Those who have undergone major surgical operations within 6 months before screening, or who plan to perform operations during the study period, and those who have undergone operations that will affect the absorption, distribution, metabolism, and excretion of drugs (except for appendicitis and hernia repair surgery).
6. Those who have received vaccination within 28 days before screening;
7. The alcohol breath test result before the test is greater than 0.0mg / 100mL, or drinking more than 14 standard units (1 standard unit contains 14g alcohol, such as 360mL beer or 45mL alcohol with 40% alcohol content) within 3 months before screening Spirits or 150mL of wine, and those who cannot accept alcohol prohibition after the selection to the entire test period;
8. Those who smoked more than 5 cigarettes per day in the 3 months before screening, or used tobacco products, nicotine products (patches, chewing gum, etc.); and those who could not accept no-smokers from the time they were selected until the entire trial;
9. Those who have a history of allergy to pepase or L-asparaginase and its related compounds and any ingredients, or who are allergic to two or more drugs (or food);
10. Drug abuse before the test and a positive drug test or a history of drug abuse within 5 years before the test (morphine, methamphetamine, ketamine, dimethylenedioxyamphetamine, tetrahydrocannabinolic acid, cocaine Etc.);
11. Those who donated or lost blood >= 400mL within 3 months before the test, or plan to donate blood or blood components within the study period or within 3 months after the end of the study;
12. The subjects (or those partners) are unwilling or unable to take one or more contraceptive measures during the test period to 3 months after the end of the test; or the subjects during the test period and within 3 months after the end of the test Planner for female insemination;
13. Those who have used any prescription drugs, non-prescription drugs, Chinese herbal medicines, health products within 28 days before the trial;
14. Study any beverages or foods that are rich in grapefruit ingredients or other substances that affect the absorption, distribution, metabolism, excretion, etc. of the drug within 48 hours before the first dose;
15. Those who have been drinking too much (more than 8 cups a day, 1 cup = 200mL) tea, coffee or caffeinated beverages in the long-term (within 3 months before screening); Food or beverages (such as coffee, strong tea, chocolate, etc.);
16. Those who can not follow the unified diet (such as intolerance to standard meals, etc.);
17. Can not tolerate venipuncture, there is a history of fainting halo;
18. Those who have significant changes in diet or exercise habits within 14 days before the first use of the study drug (such as dieting, overeating or sudden exercise without exercise habits, etc.);
19. The investigator believes that there are any circumstances that may affect the subject's informed consent or follow the protocol, or that the participant's participation in the trial may affect the outcome of the trial or its own safet.

研究实施时间：

Study execute time：

从 From 2020-05-05 00:00:00至 To 2020-06-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2020-05-05 00:00:00 至 To 2020-06-30 00:00:00

干预措施：

Interventions：

组别：

受试制剂组

样本量：

 4

Group：

Test group

Sample size：

干预措施：

培门冬酶注射液

干预措施代码：

Intervention：

asparaginase injection

Intervention code：

组别：

参比制剂组

样本量：

 4

Group：

Reference group

Sample size：

干预措施：

Oncaspar

干预措施代码：

Intervention：

Oncaspar

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 Hosptial of Xingtai Medical College

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

天冬酰胺酶活性

指标类型：

主要指标

Outcome：

activity of asparaginase

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

天冬酰胺浓度

指标类型：

主要指标

Outcome：

concentration of asparagine

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

抗培门冬酶抗体（ADA）和中和性抗体（Nab）

指标类型：

主要指标

Outcome：

analysis of anti-aspartase antibody (ADA) and neutralizing antibody (Nab)

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：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 岁 years
最大 Max age 岁 years

性别：

男性

Gender：

Male

随机方法（请说明由何人用什么方法产生随机序列）：

筛选成功的受试者按筛选号升序分配随机号，该随机号决定受试者将接受的给药。在这项研究中，随机分配表将通过SAS? 9.4 或更高版本设计和运行的计算机程序生成。

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

The successful screening subjects are assigned a random number in ascending order of the screening number, and the random number determines the dosage that the subject will receive. In this study, the random allocation table will be generated by a computer program designed and run by SAS? 9.4 or higher.

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：

本次试验数据采集与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：

This experiment uses electronic data management system(EDC) to collect and management data.

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：

  2020-05-04 22:25:26