中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400082941
最近更新日期： Date of Last Refreshed on：	2024-04-11 14:56:08
注册时间： Date of Registration：	2024-04-11 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	氨氯地平贝那普利胶囊在健康受试者中随机、开放、两制剂、单次给药、两周期、交叉空腹和餐后状态下的生物等效性试验
Public title：	Bioequivalence test of amlodipine benazepril capsules in healthy volunteers in random, open, two preparations, single administration, two cycles, cross fasting and postprandial state
注册题目简写：
English Acronym：
研究课题的正式科学名称：	氨氯地平贝那普利胶囊在健康受试者中随机、开放、两制剂、单次给药、两周期、交叉空腹和餐后状态下的生物等效性试验
Scientific title：	Bioequivalence test of amlodipine benazepril capsules in healthy volunteers in random, open, two preparations, single administration, two cycles, cross fasting and postprandial state
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：	宋浩静	研究负责人：	白万军
Applicant：	Song Haojing	Study leader：	Bai Wanjun
申请注册联系人电话： Applicant telephone：	+86 180 3373 6090	研究负责人电话： Study leader's telephone：	+86 158 3399 7197
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：	shj18033736090@163.com	研究负责人电子邮件： Study leader's E-mail：	baiwanjun0311@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：	河北省石家庄市和平西路348号	研究负责人通讯地址：	河北省石家庄市和平西路348号
Applicant address：	348 Heping Road West, Shijiazhuang, Hebei	Study leader's address：	348 Heping Road West, Shijiazhuang, Hebei
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：	河北省人民医院
Applicant's institution：	Hebei General Hospital
研究负责人所在单位：	河北省人民医院
Affiliation of the Leader：	Hebei General Hospital

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：	2022-10	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：	河北省人民医院医学伦理委员会
Name of the ethic committee：	Ethics Committee of Hebei General Hospital
伦理委员会批准日期： Date of approved by ethic committee：	2022-05-25 00:00:00
伦理委员会联系人：	鲁杨
Contact Name of the ethic committee：	Lu Yang
伦理委员会联系地址：	河北省石家庄市和平西路348号
Contact Address of the ethic committee：	348 Heping Road West, Shijiazhuang, Hebei
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 311 8598 8311	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：

河北省人民医院

Primary sponsor：

Hebei General Hospital

研究实施负责（组长）单位地址：

河北省石家庄市和平西路348号

Primary sponsor's address：

348 Heping Road West, Shijiazhuang, Hebei

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北龙海药业有限公司	具体地址：	石家庄经济技术开发区塔西大街6号
Institution hospital：	Hebei longhai drug co., ltd	Address：	No.6 Tashi Street, Shijiazhuang Economic and Technological Development Zone

经费或物资来源：

河北龙海药业有限公司

Source(s) of funding：

Hebei longhai drug co., ltd

研究疾病：

无

Target disease：

None

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：

随机交叉对照

Study design：

Cross-over

研究目的：

主要研究目的：以河北龙海药业有限公司生产的氨氯地平贝那普利胶囊（规格：氨氯地平5mg，盐酸贝那普利10mg）为受试制剂，Novartis Pharmaceuticals Corporation（诺华制药）生产的氨氯地平贝那普利胶囊（商品名：Lotrel®，规格：氨氯地平5mg，盐酸贝那普利10mg）为参比制剂，比较中国健康受试者在空腹状态下单次口服氨氯地平贝那普利胶囊的体内血药浓度及主要药代动力学参数，评价两制剂的生物等效性。次要研究目的：评价中国健康受试者在空腹状态下单次口服氨氯地平贝那普利胶囊受试制剂或参比制剂后的安全性。

Objectives of Study：

Main research purposes: Amlodipine benazepril capsules (specifications: amlodipine 5mg, benazepril hydrochloride 10mg) produced by Hebei Longhai Pharmaceutical Co., Ltd. were used as test preparations, and amlodipine benazepril capsules (trade name: Lotrel®, specifications: amlodipine 5mg, benazepril hydrochloride 10mg) produced by Novartis Pharmaceuticals Corporation were used as reference preparations. To compare the plasma concentration and main pharmacokinetic parameters of amlodipine benazepril capsules in China healthy volunteers in fasting state, and to evaluate the bioequivalence of the two preparations. Secondary research purposes: To evaluate the safety of amlodipine benazepril capsule test preparation or reference preparation in China healthy volunteers on an empty stomach.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1) The subjects fully understand the purpose, nature, methods and possible adverse reactions of the experiment, voluntarily serve as subjects, and sign the informed consent approved by the Ethics Committee;
2) Healthy male and female subjects over 18 years old (including 18 years old), with appropriate sex ratio;
3) Male weight ≥50.0kg, female weight ≥ 45.0 kg; Body mass index (BMI) is in the range of 19.0~26.0kg/m2 (including critical value);
4) Vital signs examination, the reference value range: systolic blood pressure 90~139mmHg (including the boundary value), diastolic blood pressure 60~89mmHg (including the boundary value), pulse 60~100 beats/min (including the boundary value), body temperature 36.0~37.0℃ (including the boundary value), and the research doctor judges that there is no abnormality or abnormality without clinical significance.
5) Subjects (including male subjects) have no birth plan from 1 month before screening to 6 months after the end of the trial, and have no plans to donate sperm or eggs and voluntarily take effective contraceptive measures;
6)The subjects voluntarily signed the informed consent form, and were able to communicate well with the researchers and understand and abide by the requirements of this study.

排除标准：

1)受试者有心血管系统、呼吸系统、消化系统、泌尿生殖系统、血液和淋巴系统、内分泌系统、免疫系统、精神/神经系统、骨骼肌肉及皮肤慢性疾病史或严重疾病史者（问诊）； 2)已知对氨氯地平、贝那普利或其他血管紧张素转化酶抑制剂（ACEI）药物、或其辅料有过敏史，或既往存在药物或食物过敏史者； 3)有药物依赖性水肿、血管性水肿、面部水肿病史者； 4)有吞咽困难或任何影响药物吸收的胃肠道疾病史者； 5)乳糖不耐受（喝牛奶腹泻）者或对饮食有特殊要求，不能接受统一饮食者； 6)不能耐受静脉穿刺者，有晕针晕血史者或静脉采血困难者； 7)女性受试者正处在哺乳期或妊娠检查结果阳性者； 8)实验室检查（血液分析、尿液分析+尿沉渣定量、血生化、病毒学检查、凝血四项）、体格检查、12导联心电图、胸部X片、肾动脉超声检查，研究者判断结果异常有临床意义者； 9)筛选前6个月内接受过外科手术或计划在试验期间进行手术者，以及凡接受过会影响药物吸收、分布、代谢、排泄的手术者； 10)筛选前3个月内使用过毒品或筛选前6个月内有药物滥用史或尿液药物筛查阳性者； 11)筛选前3个月内献血或大量失血（≥400mL），接受输血或使用血制品者； 12)筛选前3个月内每日吸烟量>5支或试验期间不能停止使用任何烟草类产品者； 13)筛选前3个月内每周饮酒量大于14单位（1单位≈357 mL啤酒或43 mL酒精量为40%的白酒或147 mL酒精量为12%的葡萄酒），或酒精呼气检测结果大于0mg/100ml，或试验期间不能禁酒者； 14)筛选前3个月内参加过其他药物临床试验者或非本人参加试验者； 15)筛选前1个月内接受过疫苗接种者（特殊：新冠腺病毒载体疫苗需满1个月，灭活及重组疫苗满2周），或者计划在研究期间进行疫苗接种者； 16)筛选前28天内使用过阿利吉仑、辛伐他汀、CYP3A4抑制剂（如利托那韦、茚地那韦、伊曲康唑、酮康唑、克拉霉素）、CYP3A4诱导剂（如恩杂鲁胺、苯妥英钠、利福平）、锂剂、金剂、雷帕霉素靶蛋白抑制剂（如替西罗莫司、依维莫司）、脑啡肽酶抑制剂（如沙库巴曲、沙库巴曲缬沙坦）者； 17)筛选前14天内服用了任何药物、维生素或保健品者； 18)筛选前48h内，食用过葡萄柚、柚子、火龙果、芒果影响代谢酶的水果或相关产品； 19)筛选前48h内食用过富含咖啡因（如茶、巧克力、咖啡）或富含嘌呤（如动物肝脏、海产品、香菇、肉汤）的食物或饮料，或不同意自筛选至试验结束禁止进食上述食物者； 20)有体位性低血压者[仰卧休息5min后，站立1-3min收缩压下降＞20mmHg或舒张压下降＞10mmHg（或收缩压下降＞10mmHg，并出现头晕或晕厥）]； 21) 其他研究者判定受试者有任何不适宜参加试验的情况。

Exclusion criteria：

1) The subject has a history of chronic or serious diseases of cardiovascular system, respiratory system, digestive system, genitourinary system, blood and lymphatic system, endocrine system, immune system, mental/nervous system, skeletal muscle and skin (consultation); 2) Those who are known to have allergic history to amlodipine, benazepril or other angiotensin converting enzyme inhibitor (ACEI) drugs, or their auxiliary materials, or have allergic history to drugs or foods in the past; 3) Those with a history of drug-dependent edema, vascular edema and facial edema; 4) Have a history of dysphagia or any gastrointestinal diseases that affect drug absorption; 5) People who are lactose intolerant (drinking milk and diarrhea) or have special requirements for diet and cannot accept a unified diet; 6) Those who can't tolerate venipuncture, those who have a history of fainting needle and blood, or those who have difficulty in venous blood collection; 7) Female subjects are breast-feeding or have positive pregnancy test results; 8) Laboratory examination (blood analysis, urine analysis+urine sediment quantification, blood biochemistry, virology examination and coagulation), physical examination, 12-lead electrocardiogram, chest X-ray and renal artery ultrasound examination, and the results judged by the researchers are abnormal and have clinical significance; 9) Those who have undergone surgery within 6 months before screening or are scheduled to undergo surgery during the trial, and those who have undergone surgery that will affect the absorption, distribution, metabolism and excretion of drugs; 10) Those who have used drugs within 3 months before screening or have a history of drug abuse or have positive urine drug screening within 6 months before screening; 11) Those who donated blood or lost a lot of blood (≥400mL) within 3 months before screening, received blood transfusion or used blood products; 12) Those who smoked more than 5 cigarettes per day within 3 months before screening or could not stop using any tobacco products during the test period; 13) Those who have consumed more than 14 units of alcohol per week (1 unit ≈357 mL beer or 43 mL liquor with 40% alcohol content or 147 mL wine with 12% alcohol content) in the three months before screening, or whose alcohol breath test results are more than 0mg/100ml, or who can't ban alcohol during the test; 14) Those who have participated in clinical trials of other drugs within 3 months before screening or those who have not participated in the trials themselves; 15) Those who have been vaccinated within one month before screening (special: COVID-19 adenovirus vector vaccine needs one month, inactivated and recombination vaccines needs two weeks), or those who plan to be vaccinated during the study period; 16) Alijilen, simvastatin, CYP3A4 inhibitor (such as ritonavir, indinavir, itraconazole, ketoconazole and clarithromycin), CYP3A4 inducer (such as enzalutamide, phenytoin sodium and rifampicin), lithium agent, gold agent and rapamycin target protein inhibitor (such as tissirolimus and everolimus) have been used within 28 days before screening. 17) Those who have taken any drugs, vitamins or health products orally within 14 days before screening; 18) Within 48 hours before screening, fruits or related products that affect metabolic enzymes such as grapefruit, grapefruit, pitaya and mango have been eaten; 19) Having eaten foods or drinks rich in caffeine (such as tea, chocolate and coffee) or purine (such as animal liver, seafood, mushrooms and broth) within 48 hours before screening, or disagreeing with the prohibition of eating the above foods from screening to the end of the experiment; 20) People with postural hypotension [after 5 minutes of supine rest, the systolic blood pressure drops more than >20mmHg or the diastolic blood pressure drops more than 10 mmhg after standing for 1-3 minutes (or the systolic blood pressure drops more than 10 mmhg, and dizziness or syncope occurs)]; 21)Other researchers determined that the subjects were not suitable to participate in the experiment.

研究实施时间：

Study execute time：

从 From 2022-07-12 00:00:00至 To 2023-03-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2022-07-25 00:00:00 至 To 2022-11-17 00:00:00

干预措施：

Interventions：

组别：	空腹组别A（TR）	样本量：	18
Group：	Fasting Group A (TR)	Sample size：	18
干预措施：	第一周期空腹口服受试制剂1片，第二周期服用参比制剂1片	干预措施代码：
Intervention：	One tablet of the test preparation was taken orally on an empty stomach in the first cycle, and one tablet of the reference preparation was taken in the second cycle	Intervention code：

组别：	空腹组别B (RT)	样本量：	18
Group：	Fasting Group B (RT)	Sample size：	18
干预措施：	第一周期空腹口服参比制剂1片，第二周期服用受试制剂1片	干预措施代码：
Intervention：	One tablet of reference preparation was taken orally on an empty stomach in the first cycle, and one tablet of test preparation was taken in the second cycle.	Intervention code：

组别：	餐后组别A（TR）	样本量：	28
Group：	Feding Group A (TR)	Sample size：	28
干预措施：	第一周期餐后口服受试制剂1片，第二周期餐后服用参比制剂1片	干预措施代码：
Intervention：	One tablet of the test preparation was taken orally after meals in the first cycle, and one tablet of the reference preparation was taken after meals in the second cycle.	Intervention code：

组别：	餐后组别B (RT)	样本量：	28
Group：	Feding Group B (RT)	Sample size：	28
干预措施：	第一周期餐后口服参比制剂1片，第二周期餐后服用受试制剂1片	干预措施代码：
Intervention：	Take 1 tablet of reference preparation orally after meals in the first cycle and 1 tablet of test preparation after meals in the second cycle.	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)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北省人民医院	单位级别：	三甲
Institution hospital：	Hebei General Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	峰浓度	指标类型：	主要指标
Outcome：	Cmax	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

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：	AUC0-t	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	从给药到外推至无穷的曲线下面积	指标类型：	主要指标
Outcome：	AUC0-∞	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	达峰浓度的时间	指标类型：	次要指标
Outcome：	Tmax	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	消除速率常数	指标类型：	次要指标
Outcome：	λz	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	血浆消除半衰期	指标类型：	次要指标
Outcome：	t1/2	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	残留百分比面积	指标类型：	次要指标
Outcome：	AUC_%Extrap	Type：	Secondary 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：

结束

/Completed

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	65	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）：

在研究中每名受试者接受受试制剂或参比制剂的顺序将由随机方案确定。随机方案由统计单位应用SAS（9.4或更高版本）按1:1区组随机产生。

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

In the study, the order in which each subject receives the test preparation or the reference preparation will be determined by the randomized scheme. Random schemes are randomly generated by statistical units using SAS(9.4 or higher) in 1:1 blocks.

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：	无
Blinding：	None

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）：	本次试验数据管理采用电子化数据管理系统。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)：	The data management of this experiment adopts electronic data management system.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：	电子采集和管理系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture, EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2024-04-11 14:56:03