ChiCTR2400085075 版本V1.0 版本创建时间2024/05/30 16:08:59 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：

ChiCTR2400085075 

最近更新日期：

Date of Last Refreshed on：

2024-05-30 16:08:56 

注册时间：

Date of Registration：

2024-05-30 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

二甲双胍恩格列净片在健康受试者中的单剂量、随机、开放、交叉、两制剂、两周期空腹和餐后人体生物等效性试验

Public title：

Single-dose, randomized, open, crossover, two-preparation, two-cycle fasting and postprandial bioequivalence test of metformin tablets in healthy volunteers

注册题目简写：

English Acronym：

研究课题的正式科学名称：

二甲双胍恩格列净片在健康受试者中的单剂量、随机、开放、交叉、两制剂、两周期空腹和餐后人体生物等效性试验

Scientific title：

Single-dose, randomized, open, crossover, two-preparation, two-cycle fasting and postprandial bioequivalence test of metformin tablets in healthy volunteers

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：

liuxianfang 

Study leader：

Gou Fengxue 

申请注册联系人电话：

Applicant telephone：

+86 186 3209 6620

研究负责人电话：

Study leader's telephone：

+86 177 3199 8618

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：

河北省邢台市钢铁北路618号

研究负责人通讯地址：

河北省邢台市钢铁北路618号

Applicant address：

618 Iron and Steel Road North, Xindu District, Xingtai, Hebei, China

Study leader's address：

618 Iron and Steel Road North, Xindu 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/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

XYEYCTEC-HS-173

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：

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 Colleg

伦理委员会批准日期：

Date of approved by ethic committee：

2024-04-29 00:00:00

伦理委员会联系人：

柳振芳

Contact Name of the ethic committee：

Liu Zhenfang

伦理委员会联系地址：

河北省邢台市信都区钢铁北路618号

Contact Address of the ethic committee：

618 Iron and Steel Road North, Xindu District, Xingtai, Hebei, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 319 227 9916

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 Hospital of Xingtai Medical College

研究实施负责（组长）单位地址：

河北省邢台市信都区钢铁北路618号

Primary sponsor's address：

618 Iron and Steel Road North, Xindu 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)：

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：

河北省石家庄经济技术开发区塔西大街6号

Institution
hospital：

Hebei Longhai Pharmaceutical Co., Ltd

Address：

No.6 Taxi Street, Shijiazhuang Economic and Technological Development Zone, Hebei Province

经费或物资来源：

河北龙海药业有限公司

Source(s) of funding：

Hebei Longhai Pharmaceutical Co., Ltd

Target disease：

None

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的二甲双胍恩格列净片（规格：每片含盐酸二甲双胍1000mg与恩格列净12.5mg）为受试制剂，以Boehringer Ingelheim的二甲双胍恩格列净片（规格：每片含盐酸二甲双胍1000mg与恩格列净12.5mg）为参比制剂，按生物等效性试验的有关规定，考察两制剂在健康人体内的生物等效性。 次要研究目的： 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：

Main research purposes: Taking the metformin tablets of Hebei Longhai Pharmaceutical Co., Ltd. (specifications: each tablet contains 1000mg of metformin hydrochloride and 12.5mg of engelheim) as the test preparation and the metformin tablets of Boehringer Ingelheim (specifications: each tablet contains 1000mg of metformin hydrochloride and 12.5mg of engelheim) as the reference preparation, the health of the two preparations was investigated according to the relevant provisions of bioequivalence test. Secondary research purpose: To observe the safety of test preparation and reference preparation 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)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，自愿参加本试验，并在试验开始前签署知情同意书； 2)年龄为18~55周岁（包括临界值）的健康受试者，男女性别比例适当； 3)体重指数（BMI）＝体重（kg）/身高2（m2），体重指数在19.0~26.0范围内（包括临界值）；男性受试者体重不低于50.0公斤，女性受试者重不低于45公斤； 4)受试者从签署知情同意书起至研究结束后3个月内无生育计划，且同意在此期间本人及伴侣自愿采取有效恰当的避孕措施； 5)受试者能够和研究者进行良好的沟通，并且理解和遵守本研究的各项要求。

Inclusion criteria

1) The subjects fully understand the purpose, nature, methods and possible adverse reactions of the experiment, voluntarily participate in the experiment, and sign the informed consent before the experiment begins; 2) Healthy subjects aged 18-55 (including the critical value) have an appropriate sex ratio between men and women; 3) Body mass index (BMI) = weight (kg)/ height 2(m2), and the BMI is in the range of 19.0~26.0 (including the critical value); The weight of male subjects is not less than 50.0 kg, and that of female subjects is not less than 45 kg; 4) The subject has no birth plan within 3 months from the signing of the informed consent form to the end of the study, and agrees that the subject and his/her partner will voluntarily take effective and appropriate contraceptive measures during this period; 5) Subjects can communicate well with researchers and understand and abide by the requirements of this study.

排除标准：

1)（问询）对二甲双胍、恩格列净或者本品的任何辅料成份过敏者；或过敏体质者（如对两种或以上药物、食物过敏者）； 2)（问询）有临床表现异常需排除的疾病或因素，包括但不限于神经系统、心血管系统、呼吸系统、消化系统、代谢、骨骼等系统疾病；有将危害受试者安全的因素或其他可能影响药物吸收、分布、代谢和排泄的因素，如吞咽困难者、有胃肠道疾病史者； 3)（问询）既往有低血糖发作史者，或有维生素B12缺乏病史者，或有低血压病史者，或有生殖器真菌感染或泌尿系统感染病史者，或有急慢性代谢性酸中毒病史者（包括乳酸酸中毒或酮症酸中毒），或有肝病、肾功能损害、酒精中毒或心衰病史的患者； 4)（问询）给药前 48h 内进行过碘造影者或试验期间将接受血管内注射碘化造影剂检查者； 5)（问询）给药前3个月内接受过重大手术，或计划在试验期间进行手术者； 6)（问询）不能耐受静脉穿刺者，有晕针晕血史者； 7)（问询）给药前6个月内有药物滥用史或使用过任何毒品者； 8)（问询）给药前3个月内献血或失血（≥200mL），接受输血或使用血制品者；或计划在试验期间献血或血液成分者； 9)（问询）受试者在首次服药至研究结束后3个月内有捐精、捐卵计划； 10)（问询）给药前30天内使用过任何抑制或诱导肝脏对药物代谢的药物（如：诱导剂--巴比妥类、卡马西平、苯妥英、糖皮质激素、奥美拉唑；抑制剂--SSRI类抗抑郁药、西咪替丁、地尔硫卓、大环内酯类、硝基咪唑类、维拉帕米、氟喹诺酮类、抗组胺类）者或其他任何研究者认为可能会影响研究药物药代动力学特征评价的药物（包括中药）； 11)（问询）筛选前30天使用过任何与二甲双胍有相互作用的药物（如雷诺嗪、凡他尼布、多替拉韦、西咪替丁，或唑尼沙胺、乙酰唑胺、双氯非那胺，或噻嗪类药物、皮质类固醇、酚噻嗪类、甲状腺制剂、雌激素类、口服避孕药、烟酸、拟交感神经药、钙通道阻滞药和异烟肼等）者；筛选前30天使用过任何与恩格列净有相互作用的药物（如利尿剂、胰岛素或胰岛素促泌剂、吉非罗齐、利福平、丙磺舒等）者； 12)（问询）给药前30天内接种过任何疫苗者； 13)（问询）筛选前30天内平均每天吸烟大于5支者；或不能保证从签署知情同意书起至研究结束期间停止吸烟者； 14)（问询）筛选前30天内酒精摄入量平均每天超过2个单位（1单位=360mL酒精含量为5%的啤酒，或45mL酒精含量为40%的烈酒，或150mL酒精含量为12%的葡萄酒）；或不能保证从签署知情同意书起至研究结束期间停止饮酒及酒精制品者； 15)（问询）筛选前30天内长期饮用过量茶、咖啡和/或含咖啡因的饮料（一天8杯以上，1杯=250mL）；或不能保证从签署知情同意书起至研究结束期间停止饮用茶、咖啡和/或含咖啡因的饮料者； 16)（问询）受试者在首次服药前48h内进食过可能影响药物药代动力学的特殊饮食（包括菠萝、火龙果、芒果、柚子、酸橙、杨桃、巧克力或由其制备的食物或饮料，或含咖啡因、黄嘌呤、葡萄柚（西柚）成分的食物等）； 17)（问询）对饮食有特殊要求，不能遵守统一饮食或筛选前30天内有显著不正常/特殊饮食（如节食、低钠饮食）者； 18)（问询）乳糖/半乳糖不耐受者； 19)（问询）女性受试者在给药前14天内有未采取有效、恰当避孕措施的性行为； 20)（问询）妊娠期、哺乳期妇女； 21)给药前3个月内参加过其它药物临床试验或器械临床试验，并使用试验药物或试验器械者； 22)生命体征或体格检查异常有临床意义者； 23)实验室检查（包括血常规、血生化、凝血功能、尿常规、输血前四项、妊娠检查（仅女性）），心电图检查任何项目异常并经研究者判断有临床意义者； 24)酒精呼气试验结果大于0.0mg/100mL者； 25)毒品筛查阳性者（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）； 26)受试者可能因为其他原因而不能依从方案完成本研究或研究者判定不适宜参加者。

Exclusion criteria：

1) (Inquire) Those who are allergic to metformin, englejing or any auxiliary ingredients of this product; Or people with allergies (such as those who are allergic to two or more drugs and foods); 2) (Inquiry) Diseases or factors with abnormal clinical manifestations that need to be excluded, including but not limited to diseases of nervous system, cardiovascular system, respiratory system, digestive system, metabolism, bone and other systems; There are factors that will endanger the safety of the subjects or other factors that may affect the absorption, distribution, metabolism and excretion of drugs, such as dysphagia and a history of gastrointestinal diseases; 3) (Inquiry) Those who have a history of hypoglycemia, vitamin B12 deficiency, hypotension, genital fungal infection or urinary system infection, acute or chronic metabolic acidosis (including lactic acidosis or ketoacidosis), or patients with liver disease, renal dysfunction, alcoholism or heart failure; (4) (Inquire) those who have undergone iodine contrast within 48 hours before administration or who will receive intravenous injection of iodine contrast during the trial; 5) (Inquiry) Those who have undergone major surgery within 3 months before administration, or plan to have surgery during the trial; 6) (Inquiry) Those who can't tolerate venipuncture and have a history of needle fainting and blood fainting; 7) (Inquiry) Anyone who has a history of drug abuse or used any drugs within 6 months before administration; 8) (Inquiry) Those who have donated blood or lost blood (≥200mL), received blood transfusion or used blood products within 3 months before administration; Or plan to donate blood or blood components during the trial; 9) (Inquiry) Subjects have plans to donate sperm and eggs within 3 months from the first medication to the end of the study; 10) (Inquiry) Have used any drugs that inhibit or induce the metabolism of drugs in the liver within 30 days before administration (such as:inducers-barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; Inhibitors --SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, verapamil, fluoroquinolones, antihistamines) or any other drugs (including traditional Chinese medicine) that researchers think may affect the evaluation of pharmacokinetic characteristics of the research drugs; 11) (Inquiry) Have used any drugs that interact with metformin (such as ranolazine, Fantanib, Dotiravir, cimetidine, zonisamide, acetazolamide, diclofenac, or thiazides, corticosteroids, phenothiazines, thyroid preparations, estrogens, oral contraceptives, nicotinic acid, sympathomimetic drugs, calcium channel block) 30 days before screening. Those who have used any drugs (such as diuretics, insulin or insulin secretagogue, gemfibrozil, rifampicin, probenecid, etc.) that interact with Engleggin in the first 30 days of screening; 12) (Inquiry) Anyone who has been vaccinated within 30 days before administration; 13) (Inquiry) Those who smoked more than 5 cigarettes a day on average within 30 days before screening; Or there is no guarantee that smokers will stop smoking from signing the informed consent form to the end of the study; 14) (Inquiry) The average alcohol intake in the 30 days before screening exceeded 2 units per day (1 unit =360mL of beer with 5% alcohol content, or 45mL of spirits with 40% alcohol content, or 150mL of wine with 12% alcohol content); Or can't guarantee to stop drinking and alcoholic products from the signing of the informed consent form to the end of the study; 15) Long-term drinking of excessive tea, coffee and/or caffeinated drinks within 30 days before screening (more than 8 cups a day, 1 cup = 250 ml); Or can't guarantee to stop drinking tea, coffee and/or caffeinated drinks from the signing of the informed consent form to the end of the study; 16) (Inquiry) Subjects have eaten special diets (including pineapple, pitaya, mango, grapefruit, lime, carambola, chocolate or foods or drinks made from them, or foods containing caffeine, xanthine and grapefruit (grapefruit)) that may affect the pharmacokinetics of drugs within 48 hours before taking the medicine for the first time; 17) (Inquiry) Those who have special requirements on diet, can't follow the unified diet or have significantly abnormal/special diets (such as dieting and low sodium diet) within 30 days before screening; 18) (inquiry) lactose/galactose intolerance; 19) (Inquire) whether the female subjects have had sex without taking effective and appropriate contraceptive measures within 14 days before administration; 20) (inquiry) pregnant and lactating women; 21) Those who have participated in clinical trials of other drugs or devices within 3 months before administration and used test drugs or devices; 22) Abnormal vital signs or physical examination has clinical significance; 23) Laboratory examination (including blood routine, blood biochemistry, coagulation function, urine routine, four items before blood transfusion, pregnancy examination (female only)), abnormal electrocardiogram examination and clinical significance judged by the researcher; 24) The result of alcohol breath test is greater than 0.0mg/100mL; 25) drug screening positive (morphine, methamphetamine, ketamine, methylene dioxamphetamine, tetrahydrocannabinol acid); 26) For other reasons, the subjects may not be able to complete the study according to the protocol or the researchers decide that they are not suitable for the participants.

研究实施时间：

Study execute time：

从 From 2024-05-30 00:00:00至 To 2024-09-30 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2024-05-30 00:00:00 至 To 2024-09-30 00:00:00  

干预措施：

Interventions：

组别：

组1（空腹）

样本量：

14

Group：

Group 1 (fasting)

Sample size：

干预措施：

受试制剂-参比制剂

干预措施代码：

Intervention：

Test preparation - Reference preparation

Intervention code：

组别：

组2 （空腹）

样本量：

14

Group：

Group 2 (fasting)

Sample size：

干预措施：

参比制剂-受试制剂

干预措施代码：

Intervention：

Reference preparation - Test preparation

Intervention code：

组别：

组3（餐后）

样本量：

14

Group：

Group 3 (postprandial)

Sample size：

干预措施：

受试制剂-参比制剂

干预措施代码：

Intervention：

Test preparation - Reference preparation

Intervention code：

组别：

组4（餐后）

样本量：

14

Group：

Group 4 (postprandial)

Sample size：

干预措施：

参比制剂-受试制剂

干预措施代码：

Intervention：

Reference preparation - Test preparation

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)：

邢台医专第二附属医院 

单位级别：

三级 

Institution
hospital：

The Second Affiliated Hospital of Xingtai Medical College

Level of the institution：

Tertiary

测量指标：

Outcomes：

指标中文名：

二甲双胍和恩格列净的AUC0-t

指标类型：

主要指标

Outcome：

AUC0-t of metformin and englishgin

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

二甲双胍和恩格列净的Cmax

指标类型：

主要指标

Outcome：

Cmax of metformin and englishgin

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

二甲双胍和恩格列净的AUC0-∞

指标类型：

主要指标

Outcome：

AUC0-∞of metformin and englishgin

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

二甲双胍和恩格列净的Tmax

指标类型：

次要指标

Outcome：

Tmax of metformin and englishgin

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：

正在进行

Recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 55 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）：

随机方案由统计单位应用SAS（9.3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)：

Random schemes are randomly generated by statistical units using SAS(9.3 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：

参与样本分析的研究人员应对样本保持盲法分析

Blinding：

Researchers participating in sample analysis should maintain blind sample analysis

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）：

无

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

none

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：

病历报告表

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

CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-05-30 16:08:56