ChiCTR2500098357 版本V1.0 版本创建时间2025/03/06 12:48:54 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：

 ChiCTR2500098357 

最近更新日期：

Date of Last Refreshed on：

 2025-03-06 12:47:40 

注册时间：

Date of Registration：

 2025-03-06 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

硝酸甘油舌下片在中国健康受试者中空腹状态下药代动力学比较研究

Public title：

Comparative study on pharmacokinetics of nitroglycerin sublingual tablets in fasting state in healthy Chinese subjects

注册题目简写：

English Acronym：

Comparative pharmacokinetic study of nitroglycerin sublingual tablets in a single center, randomized, open, fasting state in healthy Chinese subjects

研究课题的正式科学名称：

硝酸甘油舌下片在中国健康受试者中单中心、随机、开放、单剂量、两制剂、三周期、三序列、部分重复交叉、空腹状态下药代动力学比较研究

Scientific title：

A comparative study of the pharmacokinetics of nitroglycerin sublingual tablets in a single center, randomized, open, single dose, two preparations, three cycles, three sequences, partially repeated crossover and fasting state in healthy Chinese 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：

徐璐薇 

研究负责人：

徐璐薇 

Applicant：

Xu Luwei 

Study leader：

Xu Luwei 

申请注册联系人电话：

Applicant telephone：

 +86 15061003175

研究负责人电话：

Study leader's
telephone：

+86 15061003175

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：

 2285269498@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 283452112@qq.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：

江苏省泰州市海陵区济川东路86号

研究负责人通讯地址：

江苏省泰州市海陵区济川东路86号（东院）

Applicant address：

No.86, East Jichuan Road, Hailing District, Taizhou City

Study leader's address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

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：

泰州市中医院

Applicant's institution：

Taizhou Hospital of Traditional Chinese Medicine

研究负责人所在单位：

泰州市中医院

Affiliation of the Leader：

Taizhou Hospital of Traditional Chinese Medicine

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：

 2024-022-01

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：

泰州市中医院伦理审查委员会

Name of the ethic committee：

Taizhou Hospital of Traditional Chinese Medicine

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-06-18 00:00:00

伦理委员会联系人：

刘影

Contact Name of the ethic committee：

Liu Ying

伦理委员会联系地址：

江苏省泰州市海陵区济川东路86号（东院）

Contact Address of the ethic committee：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 523 86611963

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 1511048942@qq.com

研究实施负责（组长）单位：

泰州市中医院

Primary sponsor：

Taizhou Hospital of Traditional Chinese Medicine

研究实施负责（组长）单位地址：

江苏省泰州市海陵区济川东路86号（东院）

Primary sponsor's address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

江苏

市(区县)：

Country：

China

Province：

Jiangsu

City：

单位(医院)：

泰州市中医院

具体地址：

江苏省泰州市海陵区济川东路86号（东院）

Institution
hospital：

Taizhou Hospital of Traditional Chinese Medicine

Address：

No. 86, Jichuan East Road, Hailing District, Taizhou City, Jiangsu Province

经费或物资来源：

广州白云山明兴制药有限公司

Source(s) of funding：

Guangzhou Baiyun Mountain Mingxing pharmaceutical Co., LTD

研究疾病：

冠状动脉疾病引起的心绞痛  

Target disease：

Angina caused by coronary artery disease

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 本研究为健康受试者空腹状态下，单次口服广州白云山明兴制药有限公司研发的受试制剂硝酸甘油舌下片（规格：0.6mg）或原研单位Pfizer Phatmaceuticals LLC生产的参比制剂硝酸甘油舌下片（商品名：Nitrostat?，规格：0.6mg），考察空腹状态下受试制剂与参比制剂在健康受试者体内的药代动力学参数，比较两制剂的药代动力学。 次要研究目的 考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 This study consisted of a single oral administration of nitroglycerin subelingual tablets developed by Guangzhou Baiyunshan Mingxing Pharmaceutical Co., LTD. (specification: 0.6mg) or a reference preparation produced by Pfizer Phatmaceuticals LLC (product name: Nitrostat?, specification: 0.6mg), to investigate the pharmacokinetic parameters of the test preparation and the reference preparation in healthy subjects under the fasting state, and compare the pharmacokinetics of the two preparations. Secondary research purpose To investigate 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.年龄为18以上周岁（包含18周岁）的男性和女性，性别比例适当； 2.男性体重≥50.0kg，女性体重≥45.0kg；体重指数（BMI）在19.0~26.0kg/m^2范围内（包括临界值）； 3.健康状况：体格检查、生命体征检查、实验室检查（血常规、尿常规、血生化、凝血四项、输血前八项）、12-导联心电图检查结果正常或异常无临床意义； 4.口腔检查结果正常或不会影响舌下含服药物在口腔内的吸收； 5.在试验前两周至最后一次给药后3个月内无妊娠计划且自愿采取有效避孕措施（附录2）且无捐精、捐卵计划； 6.能够和研究者进行良好的沟通，并且理解和承诺遵守本项研究的各项要求者。

Inclusion criteria

1.Male and female over 18 years of age (including 18 years of age), with an appropriate sex ratio; 2.Male weight >=50.0kg, female weight >=45.0kg; Body mass index (BMI) in the range of 19.0~26.0kg/m^2 (including the critical value); 3.Health status: Physical examination, vital signs examination, laboratory examination (blood routine, urine routine, blood biochemistry, coagulation four items, eight items before transfusion), 12-lead electrocardiogram examination results are normal or abnormal without clinical significance; 4.Oral examination results are normal or do not affect the absorption of sublingual drugs in the oral cavity; 5.No pregnancy plan, no voluntary use of effective contraception (Appendix 2) and no sperm or egg donation plan between 2 weeks before the trial and 3 months after the last dosing; 6.Be able to communicate well with researchers and understand and commit to the requirements of the study.

排除标准：

1.已知对任一种药物、生物制剂、食物或花粉过敏，或有特异性变态反应病史史（如过敏性皮炎、哮喘、风疹、湿疹性皮炎）或为严重的过敏体质，或已知对硝酸甘油及其辅料（乳糖）过敏者，且经研究者判断有临床意义者；
2.有反复发作的口腔黏膜疾病史（如口腔溃疡、单纯疱疹性口炎、口腔黏膜白斑、扁平苔藓、牙龈炎等）或试验前14天内出现过口腔黏膜疾病、牙科手术、口腔手术伤口且没有痊愈者；
3.试验前7天内有呕吐、腹泻病史或能干扰试验结果的任何生理状况者；
4.有慢性精神疾病或精神异常者；
5.有严重贫血，或颅内压升高者；
6.经常出现体位性低血压或头痛、头晕症状者；
7.有遗传性半乳糖不耐受、乳糖酶缺乏或葡萄糖-半乳糖吸收不良病史者；
8.筛选前6个月内曾有心肌梗塞、休克或危及生命的心律失常的患者；有心力衰竭或冠心病不稳定性心绞痛的患者；
9.存在任何血液循环系统、消化系统、泌尿系统、呼吸系统、神经系统、免疫系统、内分泌系统、精神异常或代谢异常等任何慢性或严重疾病史，或可能干扰试验结果的任何其他疾病；
10.给药前3个月内接受过外科大手术，或计划在试验期间进行手术，及凡接受过影响药物药代动力学性质的手术者；
11.不能耐受静脉穿刺者，或有晕针晕血史者；
12.筛选前一年内有药物滥用史者，或筛选前6个月内使用过毒品者，包括非医疗目的反复、大量地使用各类麻醉药品和精神药物，或尿液成瘾药物吗啡、甲基安非他明（冰毒）、氯胺酮、二亚甲基双氧安非他明（摇头丸）、四氢大麻酚酸（大麻）筛查试验任何一项或多项结果为阳性者；
13.筛选前3个月内参加过或正在参加其他的药物临床试验者；
14.筛选前3个月内献血包括成分血或大量失血（≥400mL），接受输血或使用血制品者；或打算在试验期间或试验结束后3个月内献血（包括血液成份）者；
15.女性处在妊娠期、哺乳期，或血妊娠检查结果异常者；
16.在筛选前28天内使用过任何抑制或诱导肝脏对药物代谢的药物（如利福平、贯叶连翘、苯妥英、卡马西平、苯巴比妥和地塞米松、新霉素；磷酸二酯酶-5（PDE-5）抑制剂：如枸橼酸西地那非，他达拉非，盐酸伐地那非；可溶性鸟苷酸环化酶的激活剂利奥西呱等）；
17.筛选前14天内使用过任何处方药、非处方药、中草药和维生素者；
18.给药前7天内接种过疫苗者，或计划在试验期间接种疫苗者；
19.筛选前3个月内每日吸烟量大于5支，或试验期间不能停止使用任何烟草类产品者；
20.筛选前3个月内酒精摄入量平均每天超过2个单位（1单位=17.7mL乙醇，即1单位=357mL酒精量为5%的啤酒或43mL酒精量为40%的白酒或147mL酒精量为12%的葡萄酒），或酒精测试≥0mg/L者，或不同意在试验期间避免饮酒者；
21.在筛选前3个月内每天饮用过量浓茶、咖啡和/或含咖啡因的饮料（8杯以上，1杯=250mL）；
22.在筛选期7天内及服药前48h内摄取过浓茶、巧克力、咖啡或含咖啡因、含酒精、含黄嘌呤（如凤尾鱼、沙丁鱼、牛肝、牛肾等）、葡萄柚或酸橙和柚子等葡萄柚相关的柑橘类水果、杨桃、木瓜、石榴的食物或饮料者；
23.对饮食有特殊要求，不能接受统一饮食（如不能耐受牛奶、鸡蛋、黄油、培根等食物）者；
24.在研究前筛选阶段或研究用药前发生急性疾病者；
25.其它研究者判定不适宜参加本项临床研究的受试者。

Exclusion criteria：

1.People who are known to be allergic to any drug, biological agent, food or pollen, or have a history of specific allergic reactions (such as atopic dermatitis, asthma, rubella, eczematous dermatitis) or are severely allergic, or are known to be allergic to nitroglycerin and its excipiants (lactose), and are judged by the investigator to be clinically significant; 2.Have a history of recurrent oral mucosal disease (such as oral ulcer, herpes simplex stomatitis, oral leukoplakia, lichen planus, gingivitis, etc.) or oral mucosal disease, dental surgery, or oral surgical wound within 14 days before the test and did not heal; 3.Patients with a history of vomiting, diarrhea, or any physiological condition that interferes with the test results within 7 days prior to the test; 4.Chronic mental illness or mental abnormality; 5.Patients with severe anemia or elevated intracranial pressure; 6.Often appear postural hypotension or headache, dizziness symptoms; 7.People with a history of hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption; 8.Patients who had a history of myocardial infarction, shock, or life-threatening arrhythmia within 6 months prior to screening; Patients with heart failure or coronary unstable angina; 9.History of any chronic or serious medical condition of the circulatory system, digestive system, urinary system, respiratory system, nervous system, immune system, endocrine system, mental or metabolic disorders, or any other medical condition that may interfere with the test results; 10.Patients who have undergone major surgery within 3 months prior to administration, or who plan to undergo surgery during the trial period, and who have undergone surgery that affects the pharmacokinetic properties of the drug; 11.Patients who cannot tolerate venipunction, or have a history of fainting needles and fainting blood; 12.A history of drug abuse in the year preceding screening, or use of drugs in the six months preceding screening, including repeated, heavy use of narcotic drugs and psychotropic substances for non-medical purposes, Or urine addictive drugs morphine, methamphetamine (methamphetamine), ketamine, dimethylene dioxyamphetamine (ecstasy), tetrahydrocannabinol (cannabis) screening test any one or more positive results; 13.Participants who have participated or are participating in other drug clinical trials within 3 months prior to screening; 14.People who donated blood within 3 months prior to screening, including component blood or large blood loss (>=400mL), received blood transfusion or used blood products; Or intends to donate blood (including blood components) during or within 3 months after the end of the trial; 15.Women in pregnancy, breastfeeding, or abnormal blood pregnancy test results; 16.Use of any drug that inhibits or induces liver metabolism of drugs (e.g., rifampicin, hypericum perforatum, phenytoin, carbamazepine, phenobarbital and dexamethasone, neomycin) within 28 days prior to screening; Phosphodiesterase-5 (PDE-5) inhibitors: such as sildenafil citrate, tadalafil, Vardenafil hydrochloride; Soluble guanylate cyclase activator Leociguide, etc.); 17.People who have used any prescription, over-the-counter, herbal and vitamin medicines in the 14 days prior to screening; 18.Those who received the vaccine within 7 days prior to administration, or who plan to receive the vaccine during the trial; 19.Smoking more than 5 cigarettes per day in the 3 months prior to screening, or unable to stop using any tobacco products during the trial; 20.An average alcohol intake of more than 2 units per day (1 unit =17.7mL ethanol, i.e. 1 unit =357mL beer with 5% alcohol or 43mL liquor with 40% alcohol or 147mL wine with 12% alcohol) in the 3 months prior to screening, or a breathalyzer test ≥0mg/L, or who did not agree to avoid alcohol consumption during the trial; 21.Excessive consumption of strong tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup =250mL) per day in the 3 months prior to screening; 22.Ingested strong tea, chocolate, coffee or food or drink containing caffeine, alcohol, xanthine (such as anchovies, sardines, ox liver, ox kidney, etc.), grapefruit or other grapefruits related citrus fruits such as lime and pomelo, star fruit, papaya, pomegranate within 7 days of the screening period and 48 hours before taking the drug; 23.Have special dietary requirements, can not accept a unified diet (such as can not tolerate milk, eggs, butter, bacon and other foods); 24.Acute illness occurred during the pre-study screening phase or prior to study medication; 25.Subjects determined by other investigators to be unsuitable for participation in this clinical study.

研究实施时间：

Study execute time：

从 From 2024-07-29 00:00:00至 To 2025-01-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-07-29 00:00:00 至 To 2024-12-31 00:00:00

干预措施：

Interventions：

组别：

TRR组

样本量：

 3

Group：

TRR group

Sample size：

干预措施：

按照T-R-R给药顺序依次给与硝酸甘油舌下片受试制剂或参比试剂

干预措施代码：

Intervention：

Nitroglycerin subelingual tablets were administered in the order of T-R-R or reference reagent

Intervention code：

组别：

RTR组

样本量：

 3

Group：

Reference preparation - Test preparation - Reference preparation (RTR group)

Sample size：

干预措施：

按照R-T-R给药顺序依次给与硝酸甘油舌下片参比试剂或受试制剂

干预措施代码：

Intervention：

The reference reagent or the test preparation of nitroglycerin subolingua tablets was given in the R-T-R administration sequence

Intervention code：

组别：

RRT组

样本量：

 3

Group：

RRT group

Sample size：

干预措施：

按照R-R-T给药顺序依次给与硝酸甘油舌下片参比试剂或受试制剂

干预措施代码：

Intervention：

The reference reagent or the test preparation of nitroglycerin suboglossum tablets was given in the R-R-T administration sequence

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 江苏 

市(区县)：

  

Country：

China

Province：

Jiangsu

City：

单位(医院)：

 泰州市中医院 

单位级别：

 三级甲等 

Institution
hospital：

Taizhou Hospital of Traditional Chinese Medicine

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

峰浓度Cmax、药物浓度-时间曲线下面积AUC0-t、从给药到外推至无穷远时间的曲线下面积AUC0-∞

指标类型：

主要指标

Outcome：

The peak concentration Cmax, the area under the drug concentration-time curve AUC0-T, and the area under the curve from administration to extrapolation to infinity time AUC0

Type：

Primary indicator

测量时间点：

每周期采血完成后

测量方法：

实验室检查和统计学分析

Measure time point of outcome：

After each cycle of blood collection

Measure method：

Laboratory examination and statistical analysis

指标中文名：

坐位生命体征、体格检查

指标类型：

次要指标

Outcome：

Seated vital signs, physical examination

Type：

Secondary indicator

测量时间点：

每周期完成血样采集的次日

测量方法：

仪器检测

Measure time point of outcome：

The day after each cycle of blood collection

Measure method：

Instrument testing

指标中文名：

血常规、血生化、尿常规、凝血四项、血妊娠检查（女性）、12-导联心电图

指标类型：

次要指标

Outcome：

Blood routine, blood biochemistry, urine routine, blood coagulation, blood pregnancy test (female), 12-lead electrocardiogram

Type：

Secondary indicator

测量时间点：

每周期完成血样采集的次日

测量方法：

实验室检测

Measure time point of outcome：

The day after each cycle of blood collection

Measure method：

Laboratory test

指标中文名：

达峰浓度的时间Tmax、末端相的血药浓度消除速率常数λz、消除终末端半衰期t1/2、残留面积百分比AUC_%Extrap

指标类型：

次要指标

Outcome：

The time to reach the peak concentration Tmax, the elimination rate constant λz of the blood concentration of the terminal phase, the elimination half-life of the terminal terminal t1/2, and the perce

Type：

Secondary indicator

测量时间点：

每周期采血完成后

测量方法：

实验室检查和统计学分析

Measure time point of outcome：

After each cycle of blood collection

Measure method：

Laboratory examination and statistical analysis

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：

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）：

由统计单位应用SAS（9.4或更高版本）用区组随机法生成随机分配表。在筛选时，每名受试者将使用筛选号进行识别（筛选号按照签署知情同意书的先后顺序进行排序），以S+三位阿拉伯数字表示，如S001、S002、S003......，每位进行筛选的受试者对应唯一的筛选号。

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

The statistical unit applies SAS (9.4 or later) to generate a random allocation table using block randomization. During screening, each subject will be identified by a screening number (sorted in the order in which the informed consent was signed), denoted by S+ three digits such as S001, S002, S003...... , each screened subject corresponds to a unique screening number.

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：

开放标签，对评估者隐藏分组

Blinding：

Open-label study with blinded-evaluators

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）：

原始数据只用于药品申报，上传国家药品审评中心http://www.chinadrugtrials.org.cn/

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

The raw data is only used for drug declaration and uploaded to the National Center for Drug Evaluation http://www.chinadrugtrials.org.cn/

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：

数据采集：本项目数据采集/管理系统为病例报告表（CRF），CRF中包含除外部数据外方案中规定的全部数据点。 数据管理：研究室质量保证人员对数据转移文件进行抽查，保证数据准确无误。申办方根据需要，结合试验进展情况及质量控制人员/监查员的核查结果，对上述临床试验过程、样本检测过程、数据、报告和计算过程进行不同范畴的稽查。申办方和申办方委托的合同组织相关人员对本研究进行监查和稽查，均可直接在试验现场，对源数据、源文件和报告进行查阅。

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

Data acquisition: The data acquisition/management system of this project is the Case Report Form (CRF), which contains all the data points specified in the scheme except external data. Data management: The quality assurance personnel of the research office conduct spot checks on the data transfer files to ensure the accuracy of the data. According to the needs of the sponsor, in combination with the progress of the trial and the verification results of the quality control personnel/inspectors, the sponsor shall conduct the inspection of the above clinical trial process, sample testing process, data, report and calculation process in different areas. The sponsor and the relevant personnel of the contract organization entrusted by the sponsor to monitor and audit this study can consult the source data, source documents and reports directly at the test site.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-03-06 12:47:40