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：	ChiCTR2500097818
最近更新日期： Date of Last Refreshed on：	2025-02-26 09:34:13
注册时间： Date of Registration：	2025-02-26 00:00:00
注册号状态：	补注册
Registration Status：	Retrospective registration
注册题目：	中国健康受试者空腹及餐后状态下单次口服沙库巴曲缬沙坦钠片的单中心、开放、随机、两制剂、两序列、四周期、完全重复交叉人体生物等效性试验
Public title：	Single center, open, randomized, two preparations, two sequence, four cycles, complete repeated crossover human bioequivalence test of single oral sarkubachevalsartan sodium tablets on fasting and postprandial status of Chinese healthy subjects
注册题目简写：
English Acronym：
研究课题的正式科学名称：	中国健康受试者空腹及餐后状态下单次口服沙库巴曲缬沙坦钠片的单中心、开放、随机、两制剂、两序列、四周期、完全重复交叉人体生物等效性试验
Scientific title：	Single center, open, randomized, two preparations, two sequence, four cycles, complete repeated crossover human bioequivalence test of single oral sarkubachevalsartan sodium tablets on fasting and postprandial status of Chinese 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：	赵永辰	研究负责人：	赵永辰
Applicant：	Zhao Yongchen	Study leader：	Zhao Yongchen
申请注册联系人电话： Applicant telephone：	+86 312 5981186	研究负责人电话： Study leader's telephone：	+86 312 5981186
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：	zhaoyongchen69@163.com	研究负责人电子邮件： Study leader's E-mail：	zhaoyongchen69@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：	河北省保定市莲池区裕华东路212号	研究负责人通讯地址：	河北省保定市莲池区裕华东路212号
Applicant address：	No. 212, Yuhua East Road, Lianchi District, Baoding City, Hebei Province	Study leader's address：	No. 212, Yuhua East Road, Lianchi District, Baoding City, Hebei 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：	河北大学附属医院
Applicant's institution：	Hebei University Affiliated Hospital
研究负责人所在单位：	河北大学附属医院
Affiliation of the Leader：	Affiliated Hospital of Hebei 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：	HDFYLL-GCP-2024-294	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：	河北大学附属医院伦理委员会
Name of the ethic committee：	Ethics Committee of Affiliated Hospital of Hebei University
伦理委员会批准日期： Date of approved by ethic committee：	2024-09-14 00:00:00
伦理委员会联系人：	王冰
Contact Name of the ethic committee：	Wang Bing
伦理委员会联系地址：	河北省保定市莲池区裕华东路212号
Contact Address of the ethic committee：	No. 212, Yuhua East Road, Lianchi District, Baoding City, Hebei Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 312 5981630	伦理委员会联系人邮箱： Contact email of the ethic committee：	15128989120@126.com.cn

研究实施负责（组长）单位：

河北大学附属医院

Primary sponsor：

Affiliated Hospital of Hebei University

研究实施负责（组长）单位地址：

河北省保定市莲池区裕华东路212号

Primary sponsor's address：

No. 212, Yuhua East Road, Lianchi District, Baoding City, Hebei 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)：	河北	市(区县)：
Country：	China	Province：	Hebei	City：
单位(医院)：	河北大学附属医院	具体地址：	河北省保定市莲池区裕华东路212号
Institution hospital：	Affiliated Hospital of Hebei University	Address：	No. 212, Yuhua East Road, Lianchi District, Baoding City, Hebei Province

经费或物资来源：

山东鲁抗医药集团赛特有限责任公司

Source(s) of funding：

Shandong Lukang Pharmaceutical Group Saite Co., LTD

研究疾病：

心衰

Target disease：

Heart failure

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：

研究健康受试者空腹及餐后单次口服受试制剂沙库巴曲缬沙坦钠片（山东鲁抗医药集团赛特有限责任公司，规格：200mg，沙库巴曲/缬沙坦（97mg/103mg））与参比制剂沙库巴曲缬沙坦钠片（商品名：诺欣妥 ®，Novartis Pharma Schweiz AG，规格：200mg，沙库巴曲/缬沙坦（97mg/103mg））在吸收程度和速度方面是否存在差异，评价受试制剂和参比制剂在空腹及餐后状态下给药时的生物等效性，观察受试制剂和参比制剂在健康受试者中的安全性。

Objectives of Study：

To study whether there are differences in the extent and rate of absorption between a single oral dose of the test formulation Sacubitril/Valsartan Sodium Tablets (Shandong Lukang Pharmaceutical Group Set Co., Ltd., specification: 200mg, sacubitril/valsartan (97mg/103mg)) and the reference formulation Sacubitril/Valsartan Sodium Tablets (brand name: Entresto®, Novartis Pharma Schweiz AG, specification: 200mg, sacubitril/valsartan (97mg/103mg)) in healthy subjects under fasting and postprandial conditions, to evaluate the bioequivalence of the test formulation and the reference formulation when administered under fasting and postprandial conditions, and to observe the safety of the test formulation and the reference formulation 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：

Inclusion criteria

排除标准：

1)患有血液系统、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，或能干扰试验结果的任何其他疾病或生理状况者； 2)既往或目前有慢性或活动性消化道疾病/症状或既往有胃肠道手术史或研究期间计划进行胃肠道手术，影响消化吸收者； 3)有遗传性或特发性血管性水肿病或有血管性水肿病史者； 4)有直立性低血压病史者； 5)胆汁性肝硬化和胆汁淤积者； 6)有晕针或晕血史；不能耐受静脉穿刺或采血困难者； 7)筛选前3个月内接受过手术或计划在试验期间接受手术者； 8)筛选前3个月内献血或失血（200 mL及以上）、接受输血或使用血制品者，或计划在试验期间献血或献血小板者； 9)对沙库巴曲或缬沙坦过敏者，或药品的其他成份过敏者，或乳糖不耐受者（曾发生过喝牛奶腹泻者），或过敏体质者； 10)筛选前3个月内参加了任何临床试验者，或网筛不合格者； 11)过去五年内有药物滥用史，或筛选前3个月内使用过毒品，或药物滥用尿液筛查（包括吗啡、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）阳性者； 12)筛选前4周内接受过疫苗接种者，或在试验期间计划接种疫苗者； 13)筛选前4周内用过任何药物者（包括化药、保健品或中草药），包含但不限于任何改变肝药酶活性的药物（常见肝酶诱导剂：苯巴比妥、苯妥英钠、卡马西平、氨鲁米特、灰黄霉素、氨甲丙酯、苯妥英、格鲁米特、利福平、地塞米松；常见肝酶抑制剂：丙磺舒、氯丙嗪、西咪替丁、环丙沙星、甲硝唑、氯霉素、异烟肼、磺胺药）或与沙库巴曲缬沙坦有相互作用的药物（如：ACEI类、ARB类、阿利吉仑、他汀类药物、西地那非、保钾利尿剂、NSAID类、锂制剂、转运蛋白抑制剂等）； 14)既往长期饮用过量（一天8杯以上，1杯=250 mL）茶、咖啡或含咖啡因的饮料者；给药前7天内，摄入过任何富含葡萄柚、西柚汁或其他影响药物吸收、分布、代谢、排泄等的饮料或食物者；或不同意试验期间停止食用上述饮料以及食物者； 15)既往酗酒，即每周饮酒超过28个标准单位（1标准单位含14g（17.7mL）酒精，如1单位= 357 mL酒精量为 5% 的啤酒或 43 mL酒精量为 40% 的白酒或 147 mL酒精量为 12% 的葡萄酒），或筛选前6个月内经常饮酒（每周饮酒超过14个标准单位）者；或不同意试验期间禁酒者； 16)筛选前3个月内每日吸烟量＞＝5支，或不同意试验期间禁烟者； 17)女性受试者在筛选期或试验过程中正处在妊娠期、哺乳期，或女性在筛选前14天内有未保护性行为或妊娠检测结果阳性者； 18)试验期间受试者或其伴侣不愿采用一种或一种以上的非药物避孕措施（如完全禁欲、避孕套、避孕环、结扎等）进行避孕者；或在研究结束后 3个月内有生育计划或捐精、捐卵计划者； 19)筛选期研究者判断体格检查、生命体征测量、心电图检查、实验室检查包括血常规、血生化、凝血功能、尿常规、血清病毒学检查（乙型肝炎病毒表面抗原、丙型肝炎病毒抗体、梅毒螺旋体抗体、人类免疫缺陷病毒抗体）、妊娠检测（仅女性）异常有临床意义者； 20)血钾水平>5.4 mmol/L或存在高钾血症风险因素（如糖尿病、低醛固酮血症或正在接受高钾饮食）者； 21)筛选时SBP< 100 mmHg 者； 22)在筛选期发生急性疾病者； 23)不能遵守统一饮食或有吞咽困难者； 24)研究者判定不适宜参加试验者，或受试者因自身原因不能参加试验。有符合上述条件之一者，不得作为受试者入选。

Exclusion criteria：

1) Those who have a history of any chronic or serious diseases such as hematologic, circulatory, digestive, urinary, respiratory, nervous, nervous system, immune system, endocrine system, mental abnormalities or metabolic abnormalities, or any other diseases or physiological conditions that can interfere with the test results; 2) Those who have previous or current chronic or active digestive tract diseases/symptoms or have a history of gastrointestinal surgery in the past or plan to undergo gastrointestinal surgery during the study, affecting digestion and absorption; 3) Those with hereditary or idiopathic angioedema disease or a history of angioedema; 4) Patients with a history of orthostatic hypotension; 5) Patients with biliary cirrhosis and cholestasis; 6) Have a history of fainting needle or blood sickness; Those who cannot tolerate venipuncture or have difficulty in blood collection; 7) Those who have undergone surgery within 3 months before screening or plan to undergo surgery during the trial; 8) Those who donate or lose blood (200 mL or more), receive blood transfusion or use blood products, or plan to donate blood or platelets during the trial within 3 months before screening; 9) Those who are allergic to sacubitril or valsartan, or those who are allergic to other ingredients of medicines, or lactose intolerant (those who have had diarrhea from drinking milk), or those who are allergic; 10) Those who have participated in any clinical trial within 3 months before screening, or those who fail to pass the net screening; 11) Those who have a history of drug abuse in the past five years, or have used drugs within 3 months before screening, or who are positive in urine screening for drug abuse (including morphine, methamphetamine, ketamine, dimethylenedioxyamphetamine, tetrahydrocannabinolic acid); 12) Those who have received vaccination within 4 weeks before screening, or those who plan to be vaccinated during the trial; 13) Those who have used any drugs (including chemical drugs, health products or Chinese herbal medicines) within 4 weeks before screening, including but not limited to any drugs that change the activity of liver enzymes (common liver enzyme inducers: phenobarbital, phenytoin, carbamazepine, aminolutide, griseofulvin, methamethyl, phenytoin, glunomide, rifampicin, dexamethasone; Common liver enzyme inhibitors: probenecid, chlorpromazine, cimetidine, ciprofloxacin, metronidazole, chloramphenicol, isoniazid, sulfonamides) or drugs that interact with sacubitril-valsartan (such as: ACE inhibitors, ARBs, aliskiren, statins, sildenafil, potassium-sparing diuretics, NSAIDs, lithium preparations, transporter inhibitors, etc.); 14) Those who have consumed too much tea, coffee or caffeinated beverages for a long time (more than 8 cups a day, 1 cup = 250 mL) in the past; Those who have ingested any beverage or food rich in grapefruit, grapefruit juice or other beverages or foods that affect the absorption, distribution, metabolism, excretion, etc. of drugs within 7 days before administration; or those who do not agree to stop consuming the above drinks and foods during the trial; 15) Previous alcohol abuse, that is, drinking more than 28 standard units per week (1 standard unit contains 14g (17.7mL) of alcohol, such as 1 unit = 357 mL of beer with 5% alcohol or 43 mL of liquor with 40% alcohol or 147 mL of wine with 12% alcohol), or regular drinking (more than 14 standard units of alcohol per week) within 6 months before screening; or those who do not agree to abstain from alcohol during the trial; 16) The daily smoking volume within 3 months before screening>=5), or those who do not agree to stop smoking during the trial; 17) Female subjects who are pregnant or lactating during the screening period or during the test, or women who have unprotected sex or positive pregnancy test results within 14 days before screening; 18) Subjects or their partners who are unwilling to use one or more non-drug contraceptive measures (such as complete abstinence, condoms, contraceptive rings, ligation, etc.) for contraception during the trial; or those who have a fertility plan or sperm donation or egg donation plan within 3 months after the end of the study; 19) During the screening period, the investigator judged that the physical examination, vital sign measurement, electrocardiogram examination, and laboratory tests including blood routine, blood biochemistry, coagulation function, urine routine, serum virology examination (hepatitis B virus surface antigen, hepatitis C virus antibody, Treponema pallidum antibody, human immunodeficiency virus antibody), pregnancy test (female only) were abnormal and clinically significant; 20) Blood potassium level > 5.4 mmol/L or risk factors for hyperkalemia (such as diabetes, hypoaldosteronism, or being on a high-potassium diet); 21) SBP< 100 mmHg at screening; 22) Those who have acute illness during the screening period; 23) Those who cannot comply with the uniform diet or have difficulty swallowing; 24) Those who are judged by the investigator to be unsuitable to participate in the experiment, or the subjects cannot participate in the trial due to their own reasons. Those who meet one of the above conditions shall not be selected as subjects.

研究实施时间：

Study execute time：

从 From 2024-09-01 00:00:00至 To 2025-09-01 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-11-10 00:00:00 至 To 2025-09-01 00:00:00

干预措施：

Interventions：

组别：	空腹给药组	样本量：	46
Group：	Fasting dosing group	Sample size：	46
干预措施：	受试者按照1:1比例随机分配到2个给药列组(T-R-T-R组，R-T-R-T组)之一。第一周期:T-R-T-R组受试者禁食不禁水10h以上后，空腹口服1片受试制剂(T)200mg，240m温水送服，服药前1h至服药后2h内禁水(服药饮水除外)，服药4h后进食午餐，10h后进食晚餐;R-T-R-T组受试者禁食不禁水10h以上后，空股11服1片参比制剂(R，诺欣妥200mg，240mL温水送服，服药前1h至服药后2h内禁水(服药饮水除外)，服药 4h后进食午餐，10h后进食晚餐;清洗期为7天;第一、二三、四周期交替给药，用药方法同第一周期，研究者根据随机化列表为每阶段研究分配研究药物。	干预措施代码：
Intervention：	Subjects were randomly assigned to one of two dosing groups (T-R-T-R group, R-T-R-T group) in a 1:1 ratio. The first cycle: After fasting and not fasting for more than 10 hours, the subjects in the T-R-T-R group were given 1 tablet of the tested preparation (T) 200mg orally on an empty stomach, taken with 240m warm water, deprived of water from 1 h before taking the drug to 2 h after taking the drug (except for drinking water), eating lunch after 4 hours of taking the drug, and eating dinner after 10 hours; After fasting and not watering for more than 10 hours, the subjects in the R-T-R-T group took 11 tablets of the reference preparation (R, Noxinto 200mg, 240mL warm water, 1 h before and 2 h after taking the drug), they ate lunch after 4 hours of taking the medicine, and ate dinner 10 hours later; The washing period is 7 days; The first, second, third and fourth cycles are administered alternately, and the drug method is the same as that of the first cycle, and the investigator assigns the study drug to each stage of the study according to the randomization list.	Intervention code：

组别：	餐后给药组	样本量：	52
Group：	Postprandial dosing group	Sample size：	52
干预措施：	受试者按照1:1比例随机分配到两个给药列组(T-R-T-R组，R-T-R-T组)之一。第一周期:T-R-T-R组受试者禁食不禁水10h以上后，进食商脂餐，需在 30min内完成进食，自进食开始计时的第30min±1min口服1片受试制剂(T)200mg，240ml 温水送服，服药前1h至服药后2h内禁水(高脂餐谱中的饮品和给药饮水除外)，服药4h后进食午餐，10h后进食晚餐;R-T-R-T组受试者禁食不禁水10h以上后，进食高脂餐，需在30min内完成进食，自进食开始计时的第30min+1min口服1片参比制剂(R，诺欣妥*)200mg，240mL温水送服，服药前1h服药后2h内禁水(商脂餐谱中的饮品和给药饮水除外)，服药4h后进食午餐，10h后进食晚餐;清洗期为7天;第一、三、四周期交替给药，用药方法同第一周期，研究者根据随机化列表为每阶段研究分配研究药物。	干预措施代码：
Intervention：	Subjects were randomly assigned to one of two dosing groups (T-R-T-R group, R-T-R-T group) in a 1:1 ratio. The first cycle: After fasting and not fasting for more than 10 hours, the subjects in the T-R-T-R group should eat a commercial fat meal, and they need to complete the diet within 30 min, and take 1 tablet of the test preparation (T) 200mg and 240ml warm water from the 30 min ± 1 min of the starting time from the start of eating, and no water for 1 h before and 2 h after taking the drug (except for drinks and drinking water in the high-fat diet), lunch after 4 hours of taking the drug, and dinner after 10 hours; Subjects in the R-T-R-T group fasted for more than 10 hours after fasting and not watering, ate high-fat meals, and needed to complete the diet within 30 minutes, and took 200 mg of 1 tablet of reference preparation (R, Noxinto*) orally on the 30 min + 1 min from the start of eating, 240 mL of warm water, 1 h before and 2 hours after taking the drug (except for drinks and drugs in the commercial fat diet), lunch after 4 hours of taking the drug, and dinner after 10 hours; The washing period is 7 days; The first, third and fourth cycles are administered alternately, and the drug method is the same as that of the first cycle, and the investigator allocates the study drug for each stage of the study according to the randomization list.	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)：	河北大学附属医院	单位级别：	三级甲等
Institution hospital：	Affiliated Hospital of Hebei University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	药代动力学指标（达峰时间/峰浓度/消除半衰期/消除速率常数/从给药(0h)至最后一个可测血药浓度时间点的血浆药物浓度-时间曲线下面积(AUC)/从给药(0h)到外推至无穷大时间的血浆药物浓度-时间曲线下面积 (AUC.)）	指标类型：	主要指标
Outcome：	Pharmacokinetic metrics (time to peak/peak concentration/elimination half-life/elimination rate constant/area under the plasma drug concentration-time curve (AUC) from administration (0h) to the last measurable plasma concentration time point/area under the plasma drug concentration-time curve from dosing (0h) to extrapolated to infinity (AUC.) )	Type：	Primary indicator
测量时间点：		测量方法：	液相色谱串联质谱法（LC-MS/MS）对待测样品进行分析测试
Measure time point of outcome：		Measure method：	Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used for the analysis and testing of the sample.

指标中文名：	安全性评价指标（生命体征、实验室指标、ECG等）	指标类型：	次要指标
Outcome：	Safety evaluation indicators (vital signs, laboratory indicators, ECG, etc.)	Type：	Secondary 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/不良反应发生率	指标类型：	次要指标
Outcome：	Incidence of adverse events/adverse reactions	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	受试制剂/参比制剂90%置信区间	指标类型：	主要指标
Outcome：	90% confidence interval for the test preparation/reference preparation	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：

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）：

随机表由统计单位应用SAS（9.4或以上版本）的PLAN过程按1:1区组随机产生。

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

The random table was generated by the PLAN procedure of SAS (version 9.4 or higher) in a 1:1 block randomization.

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
Blinding：	Open-label study

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）：	无
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
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
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-02-26 09:33:59