ChiCTR2400089907 版本V1.0 版本创建时间2024/09/19 14:43:31 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：

ChiCTR2400089907 

最近更新日期：

Date of Last Refreshed on：

2024-09-19 14:43:27 

注册时间：

Date of Registration：

2024-09-19 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

磷酸奥司他韦干混悬剂在健康受试者中的随机、开放、单剂量、双周期、自身交叉空腹及餐后生物等效性试验

Public title：

A randomized, open-label, single-dose, double-cycle, self-crossover fasting and postprandial bioequivalence trial of oseltamivir phosphate suspension in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

磷酸奥司他韦干混悬剂在健康受试者中的随机、开放、单剂量、双周期、自身交叉空腹及餐后生物等效性试验

Scientific title：

A randomized, open-label, single-dose, double-cycle, self-crossover fasting and postprandial bioequivalence trial of oseltamivir phosphate suspension 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：

刘艳珠 

研究负责人：

王莹 

Applicant：

Yanzhu Liu 

Study leader：

Ying Wang 

申请注册联系人电话：

Applicant telephone：

+86 159 7015 3936

研究负责人电话：

Study leader's telephone：

+86 183 6712 4548

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：

lyz15970153936@163.com

研究负责人电子邮件：

Study leader's E-mail：

nancywangying@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：

杭州师范大学

研究负责人通讯地址：

杭州市红十字会医院

Applicant address：

Hangzhou Normal University

Study leader's address：

Hangzhou Red Cross Hospital

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：

杭州师范大学药学院

Applicant's institution：

College of Pharmacy, Hangzhou Normal University

研究负责人所在单位：

杭州市红十字会医院

Affiliation of the Leader：

Hangzhou Red Cross Hospital

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：

2023-013-001

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：

杭州市红十字会医院医学伦理审查委员会

Name of the ethic committee：

Hangzhou Red Cross Hospital Medical Ethics Review Committee

伦理委员会批准日期：

Date of approved by ethic committee：

2023-05-04 00:00:00

伦理委员会联系人：

王宇

Contact Name of the ethic committee：

Yu Wang

伦理委员会联系地址：

浙江省杭州市拱墅区环城东路208号

Contact Address of the ethic committee：

208 Huancheng East Road, Gongshu District, Hangzhou, Zhejiang, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 137 5813 7404

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：

杭州市红十字会医院

Primary sponsor：

Hangzhou Red Cross Hospital

研究实施负责（组长）单位地址：

浙江省杭州市拱墅区环城东路208号

Primary sponsor's address：

208 Huancheng East Road, Gongshu District, Hangzhou, Zhejiang, 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)：

浙江

市(区县)：

杭州

Country：

China

Province：

Zhejiang

City：

Hangzhou

单位(医院)：

杭州市红十字会医院

具体地址：

浙江省杭州市拱墅区环城东路208号

Institution
hospital：

Hangzhou Red Cross Hospital

Address：

208 Huancheng East Road, Gongshu District, Hangzhou, Zhejiang, China

经费或物资来源：

申办方支付

Source(s) of funding：

Sponsor's payment

Target disease：

Influenza

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：

主要研究目的：以济南同路医药科技发展有限公司研制的磷酸奥司他韦干混悬剂（规格：6 mg/mL）为受试制剂，按生物等效性研究的有关规定，与Roche Registration GmbH生产的磷酸奥司他韦干混悬剂（规格：6 mg/mL，商品名：Tamiflu?，参比制剂）对比在健康人体内的相对生物利用度，考察两制剂的人体生物等效性。 次要研究目的：比较磷酸奥司他韦干混悬剂受试制剂和参比制剂（商品名：Tamiflu?）在健康受试者中的安全性。  

Objectives of Study：

Main research objectives: oseltamivir phosphate suspension (specification: 6 mg/mL) developed by Jinan Tonglu Medical Technology Development Co., Ltd. was used as the test preparation, and oseltamivir phosphate suspension (specification: 6 mg/mL) produced by Roche Registration GmbH was used as the test preparation according to the relevant provisions of bioequivalence study. Tamiflu?, the reference formulation) were compared with their relative bioavailability in healthy subjects to investigate their human bioequivalence. Secondary study objective: To compare the safety of oseltamivir phosphate dry suspension between the test formulation and the reference formulation (Tamiflu?) 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：

满足全部入选标准方可入选： 1)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，自愿作为受试者，并在任何研究程序开始前签署知情同意书。 2)年龄为 18 周岁以上（包括 18 周岁）的健康男性和女性受试者； 3)男性体重≥50.0 kg，女性体重≥45.0 kg；体重指数（BMI）在 19.0~26.0 kg/m2范围内（包括临界值），BMI=体重（kg）/身高 2（m）2； 4)生命体征、体格检查、12 导联心电图和实验室检查（血常规、尿常规、血生化、病毒筛查、凝血功能、女性血妊娠）正常或研究医生判断异常无临床意义； 5)受试者自签署知情同意书至最后一次给药后 3 个月内无生育计划且自愿采取有效避孕措施，且无捐精、捐卵计划。

Inclusion criteria

To be included, all eligibility criteria were met: 1) The subjects were fully aware of the purpose, nature, methods, and possible adverse reactions of the trial, volunteered to serve as subjects, and signed an informed consent form before the start of any study procedure. 2) the age of 18 one full year of life above (including 18 one full year of life) of healthy male and female subjects; 3) male weight 50.0 kg, or female weight 45.0 kg or more; Body mass index (BMI) in the range of 19.0-26.0 kg/m2 (including critical value), BMI= weight (kg)/height 2 (m) 2; 4) of vital signs, physical examination, 12 lead electrocardiogram (ecg) and laboratory tests (blood routine, routine urine and blood biochemistry, screening, blood coagulation function, women pregnancy) normal or research doctors determine abnormal without clinical significance; 5) The subjects had no plans to have children within 3 months after signing the informed consent and voluntarily took effective contraceptive measures, and had no plans to donate sperm or eggs.

排除标准：

满足1项以下排除标准即排除： 1)对磷酸奥司他韦或其辅料过敏，或有过敏体质（如：哮喘、荨麻疹、湿疹等过敏性疾病史等），或有药物、食物过敏史且经研究者判断不宜入组者； 2)患有可能影响试验安全性、影响药物体内过程，或可使依从性减低的疾病或病史，包括但不限于胃肠道、肾、肝、肺、神经、血液、内分泌、肿瘤、免疫、精神或心脑血管疾病者； 3)筛选前 3 个月内接受过手术，或者计划在研究期间进行手术，及凡接受过会影响药物吸收、分布、代谢、排泄的手术者； 4)静脉穿刺困难，或不能耐受静脉穿刺，或有晕针晕血史者； 5)有吸毒史或药物滥用史，或药物滥用筛查（吗啡、甲基安非他明、氯胺酮、四氢大麻酚酸、二亚甲基双氧安非他明）阳性者； 6)对饮食有特殊要求，或乳糖、果糖、山梨醇不耐受者，或喝牛奶易腹泻者，或试验期间不能遵守统一饮食者； 7)筛选前 3 个月内参加过其他的药物或器械临床试验或非本人来参加临床试验者； 8)筛选前 3 个月内献血（包括成分血）或大量失血（≥400 mL，女性正常生理期失血除外），或接受输血或使用血制品者； 9)筛选前 3个月每日吸烟量大于 5支，或试验期间不能停止使用任何烟草类产品者； 10) 筛选前 3 个月内每周饮酒量大于 14 单位（1 单位=360 mL 啤酒或 45 mL酒精量为 40%的烈酒或 150 mL 葡萄酒），或试验期间不能禁酒者； 11)筛选前 3 个月内每天饮用过量茶、咖啡或富含咖啡因的饮料（8 杯以上，1杯=250 mL）者； 12)筛选前 1 个月内有饮食不规律行为（例如节食、暴食、低钠等）； 13)筛选前 14 天内使用了任何处方药、非处方药、中草药或保健品者； 14)筛选前 1 个月内接受过疫苗接种，或计划在试验期间接种疫苗者； 15)酒精呼气试验结果显示血液酒精浓度大于 0 mg/100 mL 者； 16)女性受试者处于怀孕期或哺乳期； 17)不能承诺在第一周期和第二周期入住 I 期病房前 3 天至入住期间不摄取火龙果、芒果、柚子、酸橙、杨桃或由其制备的食物或饮料，不摄取巧克力及任何含咖啡因（如咖啡、浓茶、可乐等）的饮料者； 18)经研究者判断不宜入组的其他情况。

Exclusion criteria：

Those who met one of the following exclusion criteria were excluded: 1) Patients who were allergic to oseltamivir phosphate or its accessories, or had allergic constitution (such as asthma, urticaria, eczema and other allergic diseases), or had a history of drug or food allergy and were judged by the investigators to be unsuitable for enrollment; 2) have any disease or medical history that may affect the safety of the trial, affect the internal course of the drug, or may reduce adherence, including but not limited to gastrointestinal, renal, hepatic, pulmonary, neurological, hematologic, endocrine, oncologic, immunologic, psychiatric, or cardio-cerebrovascular diseases; 3) patients who underwent surgery within 3 months before screening or planned to undergo surgery during the study, and those who underwent surgery that may affect drug absorption, distribution, metabolism, or excretion; 4) difficult venipuncture, or can not tolerate venipuncture, or have a history of dizzy with needles and blood; 5) having a history of drug use or drug abuse, or screening positive for drug abuse (morphine, methamphetamines, ketamine, tetrahydrocannabinol, dimethylenedioxyamphetamine); 6) do you have any special dietary requirements, or, fructose, sorbitol, lactose intolerance, or drink milk easy to diarrhea, or during the test cannot observe unified diet; 7) screening within 3 months before clinical trials involved in other drugs or equipment or not to participate in clinical subjects; 8) within 3 months prior to screening blood donation (including the component of blood) or massive blood loss (or 400 mL, female except normal physiology period of blood), or receive a blood transfusion or use of blood products; 9) who smoked more than 5 cigarettes per day in the 3 months before screening, or who could not stop using any tobacco products during the study; 10) drank more than 14 units of alcohol per week (1 unit =360 mL of beer or 45 mL of 40% spirits or 150 mL of wine) in the 3 months before screening, or could not abstain from alcohol during the study; 11) consuming excessive amounts of tea, coffee or caffeine-rich beverages (> 8 cups, 1 cup =250 mL) per day in the previous 3 months; 12) within a month before the screening have irregular diet behavior (such as diet, gluttony, low sodium, etc.); 13) who had used any prescription drug, over-the-counter drug, herbal medicine, or health supplement within 14 days before screening; 14) were vaccinated within 1 month before screening or were planning to be vaccinated during the trial; 15) blood alcohol concentration (BAC) > 0 mg/100 mL; 16) the female subjects were pregnant or lactating; 17) cannot promise in the first cycle and the second cycle in stage I ward to check-in without eating during 3 days before the dragon fruit, mango, pomelo, lime, carambola, or by the preparation of food or drink, no caffeine intake of chocolate and (such as coffee, strong tea, coke, etc.) of beverage; 18) other conditions judged by the investigator to be ineligible for enrollment.

研究实施时间：

Study execute time：

从 From 2023-06-26 00:00:00至 To 2023-08-02 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-06-26 00:00:00 至 To 2023-07-02 00:00:00  

干预措施：

Interventions：

组别：

空腹Ⅰ组（T-R）

样本量：

25

Group：

Fasting Group Ⅰ(T-R)

Sample size：

干预措施：

受试者禁食过夜至少10 h后单次给药，T-R组受试者第一周期空腹单次口服受试制剂（T）75 mg（12.5 mL，6 mg/mL），第二周期空腹单次口服参比制剂（R，Tamiflu）75 mg（12.5 mL，6 mg/mL），约227.5 mL温水送服。

干预措施代码：

Intervention：

Subjects in the T-R group received 75 mg (12.5 mL, 6 mg/mL) of the test formulation (T) in a fasting single dose in the first cycle and 75 mg (12.5 mL, 6 mg/mL) of the reference formulation (R, Tamiflu) in a fasting single dose in the second cycle. About 227.5 mL of warm water.

Intervention code：

组别：

空腹Ⅱ组（R-T）

样本量：

25

Group：

Fasting Group Ⅱ(R-T)

Sample size：

干预措施：

受试者禁食过夜至少10 h后单次给药，R-T组受试者第一周期空腹单次口服参比制剂（R，Tamiflu）75 mg（12.5 mL，6 mg/mL），第二周期空腹单次口服受试制剂（T）75 mg（12.5 mL，6 mg/mL），约227.5 mL温水送服。

干预措施代码：

Intervention：

Subjects in the R-T group received 75 mg (12.5 mL, 6 mg/mL) of the reference formulation (R, Tamiflu) orally in a fasting single dose in the first cycle, 75 mg (12.5 mL, 6 mg/mL) of the test formulation (T) orally in a fasting single dose in the second cycle, and 75 mg (12.5 ml, 6 mg/ ml) of the reference formulation (R, Tamiflu) orally in the second cycle. About 227.5 mL of warm water.

Intervention code：

组别：

餐后Ⅰ组（T-R）

样本量：

18

Group：

Fed Group Ⅰ(T-R)

Sample size：

干预措施：

T-R组受试者第一周期在开始进食高脂高热餐后30 ± 0.5 min单次口服受试制剂（T）75 mg（12.5 mL，6 mg/mL），第二周期在开始进食高脂高热餐后30 ± 0.5 min单次口服参比制剂（R，Tamiflu）75 mg（12.5 mL，6 mg/mL），约227.5 mL温水送服。

干预措施代码：

Intervention：

Participants in the T-R group received 75 mg (12.5 mL, 6 mg/mL) of the test formulation (T) in a single oral dose 30 ± 0.5 min after the start of a high-fat and high-calorie meal in cycle 1, and a single oral dose of the reference formulation (R, 6 mg/ ml) in cycle 2 30 ± 0.5 min after the start of a high-fat and high-calorie meal in cycle 2. Tamiflu ) 75 mg (12.5 mL, 6 mg/mL), 227.5 mL warm water.

Intervention code：

组别：

餐后Ⅱ组（R-T）

样本量：

18

Group：

Fed Group Ⅱ(R-T)

Sample size：

干预措施：

R-T组受试者第一周期在开始进食高脂高热餐后30 ± 0.5 min单次口服参比制剂（R，Tamiflu）75 mg（12.5 mL，6 mg/mL），第二周期在开始进食高脂高热餐后30 ± 0.5 min单次口服受试制剂（T）75 mg（12.5 mL，6 mg/mL），约227.5 mL温水送服。

干预措施代码：

Intervention：

Subjects in the R-T group received a single oral dose of the reference formulation (R, Tamiflu) 75 mg (12.5 mL, 6 mg/mL) 30 ± 0.5 min after the start of the high-fat and high-calorie meal in cycle 1, and those in the R-T group received a single oral dose of the reference formulation (R, Tamiflu?) 75 mg (12.5 ml, 6 mg/ ml). In the second cycle began eating high-fat hot meal 30 + / - 0.5 min after a single oral preparations of subjects (T) 75 mg (12.5 mL, 6 mg/mL), 227.5 mL warm water.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 浙江 

市(区县)：

 杭州 

Country：

China 

Province：

Zhejiang 

City：

Hangzhou 

单位(医院)：

杭州市红十字会医院 

单位级别：

三甲 

Institution
hospital：

Hangzhou Red Cross Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

奥司他韦的峰浓度

指标类型：

主要指标

Outcome：

Peak concentrations of oseltamivir(Cmax)

Type：

Primary indicator

测量时间点：

测量方法：

根据血药浓度-时间实测数据直接获得

Measure time point of outcome：

Measure method：

The measured data were obtained directly according to the blood concentration and time

指标中文名：

从给药到可检测最低血药浓度的时间内曲线下面积

指标类型：

主要指标

Outcome：

Area under the curve for the time from administration to the lowest detectable blood concentration(AUC0-t)

Type：

Primary indicator

测量时间点：

测量方法：

通过线性梯形法则计算

Measure time point of outcome：

Measure method：

It is calculated by the linear trapezoidal rule

指标中文名：

从给药到外推至无穷远时间的曲线下面积

指标类型：

主要指标

Outcome：

Area under the curve for the time from drug administration to extrapolation to infinity(AUC0-∞)

Type：

Primary indicator

测量时间点：

测量方法：

AUC0-∞=AUC0-t+Ct/λz，Ct是最后可测量浓度，λz是消除速率常数

Measure time point of outcome：

Measure method：

AUC0-∞=AUC0-t+Ct/λz, where Ct is the last measurable concentration and λz is the elimination rate constant

指标中文名：

达峰浓度的时间

指标类型：

次要指标

Outcome：

Time to peak concentration(Tmax)

Type：

Secondary indicator

测量时间点：

测量方法：

根据血药浓度-时间实测数据直接获得

Measure time point of outcome：

Measure method：

The measured data were obtained directly according to the blood concentration and time

指标中文名：

消除速率常数

指标类型：

次要指标

Outcome：

Elimination rate constant(λz)

Type：

Secondary indicator

测量时间点：

测量方法：

使用线性回归方法计算的半对数药时曲线终末段的斜率，结果取斜率的相反数

Measure time point of outcome：

Measure method：

The slope of the end segment of the semilogarithmic curve was calculated using the linear regression method, and the result was taken as the inverse of the slope

指标中文名：

消除终末端半衰期

指标类型：

次要指标

Outcome：

Terminal terminal half-life was eliminated(t1/2z)

Type：

Secondary indicator

测量时间点：

测量方法：

按照ln2/λz计算

Measure time point of outcome：

Measure method：

It is calculated as ln2/λz

指标中文名：

残留面积百分比

指标类型：

次要指标

Outcome：

Residual area percentage(AUC_%Extrap)

Type：

Secondary indicator

测量时间点：

测量方法：

以[（AUC0-∞-AUC0-t）/AUC0-∞]×100%计算

Measure time point of outcome：

Measure method：

It was calculated as [(AUC0-∞-AUC0-t) /AUC0-∞]×100%

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血浆

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

征募研究对象情况：

Recruiting status：

结束

/Completed

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）：

研究者将判断受试者的入选资格，合格受试者按照筛选号由小到大顺序分配随机号。试验第-1天进行随机，合格受试者按照筛选号从小到大的顺序获得随机号，并根据随机表随机分配进入不同给药序列（T-R组或R-T组）。随机表由统计单位南京英锋医药科技有限公司采用SAS 9.4版本软件，按1:1区组随机化方法生成，种子数为20230625，区组长度为10，区组数为5。空腹试验实际入组50例受试者，随机化编号为K001~K050；餐后试验实际入组36例受试者，随机化编号为C001~C036。

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

Eligibility was determined by the investigator, and eligible participants were assigned a random number in descending order of screening number. Randomization was performed on day -1 of the trial. Eligible subjects were randomly assigned to different dosing sequences (T-R group or R-T group) according to the random table. The randomization table was generated by the statistical unit Nanjing Yingfeng Medical Technology Co., Ltd. using SAS version 9.4 software according to the 1:1 block randomization method, the seed number was 20230625, the block length was 10, and the block number was 5. A total of 50 subjects were enrolled in the fasting trial, and the randomization number was K001-K050. A total of 36 participants were enrolled in the postprandial trial, with randomization numbers C001-C036.

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：

本次临床研究为开放性研究，除生物样本分析测试人员外，其他人员如临床研究者、项目管理人员、项目监查人员、数据管理及统计分析人员等均不设盲，分析测试人员将采用盲态分析，在样本分析过程中不知道受试者每周期的给药制剂。

Blinding：

This clinical study is an open study. Except for the biological sample analysis and testing personnel, other personnel such as clinical investigators, project management personnel, project monitoring personnel, data management and statistical analysis personnel are not blinded.

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

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）：

太美 eCollect EDC V5，https://www.trialos.com.cn/login/

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

TaiMei eCollect EDC V5,https://www.trialos.com.cn/login/

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：

太美 eCollect EDC V5，https://www.trialos.com.cn/login/

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

TaiMei eCollect EDC V5,https://www.trialos.com.cn/login/

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2024-09-19 14:43:27