ChiCTR2400089810 版本V1.0 版本创建时间2024/09/18 08:57:29 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：

 ChiCTR2400089810 

最近更新日期：

Date of Last Refreshed on：

 2024-09-18 08:57:11 

注册时间：

Date of Registration：

 2024-09-18 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

评价ABP2111Na片在超重/肥胖受试者中的安全性、耐受性、药代动力学及药效动力学特征的随机、双盲、安慰剂对照、多次给药剂量递增的Ⅱa期临床研究

Public title：

A Randomised, Double-Blind, Placebo-Controlled, Multiple Administration Dose Escalation Phase IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of ABP2111Na Tablets in Overweight/Obese Subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评价ABP2111Na片在超重/肥胖受试者中的安全性、耐受性、药代动力学及药效动力学特征的随机、双盲、安慰剂对照、多次给药剂量递增的Ⅱa期临床研究

Scientific title：

A Randomised, Double-Blind, Placebo-Controlled, Multiple Administration Dose Escalation Phase IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profile of ABP2111Na Tablets in Overweight/Obese 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：

王海平 

研究负责人：

纪立农 

Applicant：

Haiping Wang 

Study leader：

Linong JI 

申请注册联系人电话：

Applicant telephone：

 +86 133 8158 8683

研究负责人电话：

Study leader's
telephone：

+86 139 1097 8815

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：

 hpwang@zannan.com

研究负责人电子邮件：

Study leader's E-mail：

 jiln@bjmu.edu.cn

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：

上海市闵行区光中路133弄99号

研究负责人通讯地址：

北京市西城区西直门南大街11号

Applicant address：

99 Lane133 Guangzhong RD, Shanghai, P.R. China

Study leader's address：

No.11 Xizhimen South Street, Xicheng District, Beijing, 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：

上海爱博医药科技有限公司

Applicant's institution：

Shanghai AB PharmaTech Ltd.

研究负责人所在单位：

北京大学人民医院

Affiliation of the Leader：

Peking University People's 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：

 2024PHC042-001

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：

北京大学人民医院伦理审查委员会

Name of the ethic committee：

Ethics Review Committee of Peking University People's Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-09-06 00:00:00

伦理委员会联系人：

丛翠翠

Contact Name of the ethic committee：

Cuicui Cong

伦理委员会联系地址：

北京市西城区西直门南大街11号

Contact Address of the ethic committee：

No.11 Xizhimen South Street, Xicheng District, Beijing, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 10 8832 4516

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：

北京大学人民医院

Primary sponsor：

Peking University People's Hospital

研究实施负责（组长）单位地址：

北京市西城区西直门南大街11号

Primary sponsor's address：

No.11 Xizhimen South Street, Xicheng District, Beijing, 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)：

上海市

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海爱博医药科技有限公司

具体地址：

上海市闵行区光中路133弄99号

Institution
hospital：

Shanghai AB PharmaTech Ltd.

Address：

99 Lane133 Guangzhong RD, Shanghai, P.R. China

经费或物资来源：

上海爱博医药科技有限公司

Source(s) of funding：

Shanghai AB PharmaTech Ltd.

研究疾病：

用于超重或肥胖人群的体重管理  

Target disease：

Weight management in overweight or obese people

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：

 II期临床试验 

Study phase：

2

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

主要目的： 评价超重/肥胖受试者多次口服ABP2111Na片的安全性和耐受性； 次要目的： 1）评价超重/肥胖受试者多次口服ABP2111Na片的药代动力学（PK）特征； 2）评价超重/肥胖受试者多次口服ABP2111Na片药效动力学（PD）； 3）初步探索ABP2111Na片控制体重的有效性，为后期临床研究提供依据； 4）初步评估ABP2111Na片在超重/肥胖受试者的心脏安全性，包括校正QT间期（QTc）延长的可能性，并评估PK/QTc关系。  

Objectives of Study：

Primary Objective: To evaluate the safety and tolerability of multiple oral doses of ABP2111Na tablets in overweight/obese subjects; Secondary Objectives: 1) To evaluate the pharmacokinetic (PK) profile of multiple oral doses of ABP2111Na tablets in overweight/obese subjects; 2) To evaluate the pharmacokinetics (PD) of multiple oral doses of ABP2111Na tablets in overweight/obese subjects; (3) To preliminarily explore the effectiveness of ABP2111Na tablets in controlling body weight and to provide a basis for later clinical studies; 4) Preliminary assessment of the cardiac safety of ABP2111Na tablets in overweight/obese subjects, including the possibility of correcting for QT interval (QTc) prolongation and evaluating the PK/QTc relationship.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

符合以下所有条件者，才能入组： (1) 年龄18~60周岁（含18及60周岁），性别不限； (2) 体重指数（BMI）≥28 kg/m2伴随或不伴随合并疾病，或BMI≥24 kg/m2且<28 kg/m2并合并体重相关并发症，如血脂异常； (3) 筛选前12周内体重稳定者（体重变化<5%，体重变化=[最大体重-最小体重]/最大体重；基于受试者自我报告）； (4) 能够理解本研究的程序和方法，愿意严格遵守临床研究方案完成本研究，并自愿签署知情同意书。

Inclusion criteria

Only those who meet all of the following conditions can be enrolled: (1) Age 18-60 years (inclusive of 18 and 60 years) and gender; (2) Body mass index (BMI) ≥28 kg/m2 with or without concomitant comorbidities, or BMI ≥24 kg/m2 and <28 kg/m2 with concomitant weight-related complications such as dyslipidaemia; (3) Stable weight (weight change <5%, weight change = [maximal weight - minimal weight]/maximal weight; based on subject self-report) in the 12 weeks prior to screening; (4) Able to understand the procedures and methods of this study, willing to complete the study in strict compliance with the clinical study protocol, and voluntarily signing the informed consent form.

排除标准：

符合以下条件之一者，不能入组： (1) 既往诊断为内分泌疾病或单基因突变引起的肥胖，包括但不限于下丘脑性肥胖、垂体性肥胖、甲状腺功能减退性肥胖、库欣综合征、胰岛细胞瘤、肢端肥大症； (2) 已知对本品或本品中的任何辅料成分有过敏者或过敏体质者； (3) 既往诊断为1型糖尿病、2型糖尿病或其他特殊类型糖尿病者； (4) 存在或既往存在可能影响受试者安全或研究结果判定的血液学疾病、肿瘤、肾脏疾病、内分泌疾病、肺部疾病、胃肠道疾病、心血管疾病、肝脏疾病、精神病、神经系统疾病； (5) 患有髓性甲状腺癌或多发性内分泌腺瘤综合征2型疾病，或具有该类疾病家族史的志愿者； (6) 既往有胰腺炎病史或有症状的胆囊疾病者； (7) 既往有增殖性视网膜病史和黄斑病史者； (8) 存在精神疾病史或当前存在精神疾病、存在中重度或重度抑郁状态，或认为有重大自杀风险； (9) 实验室检查项符合以下任一标准：血红蛋白（Hb）<110 g/L（男性）或<100 g/L（女性）；淀粉酶或脂肪酶＞1.5×ULN；甘油三酯>5.6 mmol/L、低密度脂蛋白胆固醇（LDL-C）≥4.40 mmol/L；eGFR<60 mL/min/1.73m^2（根据简化MDRD公式计算）；谷丙转氨酶（ALT）或谷草转氨酶（AST）≥1.5×ULN，总胆红素（TBIL）≥1.5×ULN（Gilbert综合征受试者若直接胆红素＜1×ULN可以参加本研究）；降钙素≥50 ng/L；促甲状腺激素＞6 mIU/L或＜0.4 mIU/L；糖化血红蛋白（HbA1c）≥6.5%；空腹血浆血糖（FPG）≥7.0 mmol/L； (10) 吞咽困难，或有影响胃肠道吸收的疾病（如炎症性肠病、活动性溃疡），或接受过可导致吸收不良的胃肠道手术，或长期接受对胃肠蠕动有影响的药物/治疗[如接受过减肥手术或操作（如胃束带术）]者； (11) 筛选前存在低血糖病史者； (12) 筛选前12周内，使用过以下任何一种药物或治疗：1）二肽基肽酶-4（DPP-4）抑制剂、钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂、二甲双胍、胰岛素促泌剂、噻唑烷二酮（TZD）、胰岛素等口服或注射降糖药；2）任何批准或未被批准的减重药物（如：奥利司他、氯卡色林、芬特明/托吡酯、纳曲酮/安非他酮、司美格鲁肽、艾塞那肽、利拉鲁肽、贝拉鲁肽、洛塞那肽、替尔泊肽等）或影响体重的中草药、保健品、代餐等；3）使用过可能导致体重明显改变的药物，包括持续1周以上的全身性（即静脉、口服或关节内给药）糖皮质激素；三环类抗抑郁药物；抗精神病或抗癫痫类药物（如：米帕明、阿米替林、米氮平、帕罗西汀、苯乙肼、盐酸氯丙嗪、氯氮平、奥氮平，戊酸及其衍生物，锂制剂，甲硫哒嗪）等； (13) 筛选前2周内曾服用过任何药物（包括任何处方药、非处方药、中草药和维生素）者（稳定服用降压药物者除外）； (14) 具有临床意义的12导联心电图（ECGs）异常或男性QTc≥450 ms、女性≥470 ms者； (15) 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，以及但凡接受过会影响药物吸收、分布、代谢、排泄的手术者（阑尾炎手术除外）； (16) 筛选前3个月内饮食或运动习惯上有重大变化； (17) 存在肢体畸形或残缺，无法准确确定身高、体重等指标； (18) 筛选前3个月内有酒精滥用史[每周饮用酒精超过14个单位者(1单位≈360mL啤酒或45mL酒精量为40%的烈酒或150mL葡萄酒)]；或筛选时、或入院时酒精呼气研究检测阳性者； (19) 筛选前3个月内，每天吸烟超过5支或摄入与之等量的尼古丁或尼古丁替代品； (20) 给药前3个月内参加过任何药物或医疗器械的临床试验者； (21) 筛选前3个月内有献血或大量失血者（≥400 mL）或输血或输入血制品者； (22) 给药前2天或试验期间不禁烟酒，饮用含黄嘌呤或咖啡因的饮料（如巧克力、咖啡、茶、可乐等），进行剧烈运动，或有其他影响药物吸收、分布、代谢、排泄因素者； (23) 首次给药前尿药筛阳性者或有药物滥用史（如吗啡、大麻、甲基安非他明、二亚甲基双氧安非他明、氯胺酮等）； (24) 筛选时人类免疫缺陷病毒（HIV）抗体检测阳性或乙肝表面抗原阳性、丙型肝炎抗体、梅毒螺旋体抗体检查阳性； (25) 筛选前1个月内接种过疫苗，或计划在试验期间接种疫苗者； (26) 哺乳期妇女，以及男性受试者（或其伴侣）或女性受试者在研究前30天至研究结束后6个月内有妊娠计划或捐精、捐卵计划，不愿采取有效的避孕措施者；筛选期间血清妊娠检查结果阳性者； (27) 研究者判断其他原因不适合参加本临床试验者。

Exclusion criteria：

Those who meet one of the following criteria are not eligible for enrolment: (1) Pre-existing diagnosis of obesity due to endocrine disease or single gene mutation, including, but not limited to, hypothalamic obesity, pituitary obesity, hypothyroid obesity, Cushing's syndrome, pancreatic islet cell tumour, acromegaly; (2) Known hypersensitivity or allergy to the product or any of the excipient ingredients in the product; (3) Persons with a pre-existing diagnosis of type 1 diabetes mellitus, type 2 diabetes mellitus, or other specific types of diabetes mellitus; (4) Presence or previous presence of haematological disorders, neoplasms, renal disorders, endocrine disorders, pulmonary disorders, gastrointestinal disorders, cardiovascular disorders, hepatic disorders, psychiatric disorders, neurological disorders, which may affect the safety of the subject or the determination of the results of the study; (5) Volunteers with medullary thyroid cancer or multiple endocrine adenoma syndrome type 2 disease, or a family history of such disease; (6) Persons with a prior history of pancreatitis or symptomatic gallbladder disease; (7) Persons with a prior history of proliferative retinopathy and macular disease; (8) A history of or current mental illness, the presence of a moderately severe or major depressive state, or a perceived significant risk of suicide; (9) Laboratory test items that meet any of the following criteria: haemoglobin (Hb) <110 g/L (males) or <100 g/L (females); amylase or lipase >1.5 × ULN; triglycerides >5.6 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥4.40 mmol/L; and an eGFR <60 mL/min/1.73m^2 ( calculated according to the simplified MDRD formula); alanine aminotransferase (ALT) or aminotransferase (AST) ≥1.5×ULN, and total bilirubin (TBIL) ≥1.5×ULN (Gilbert's syndrome subjects who had a direct bilirubin of <1×ULN were allowed to participate in this study); calcitonin ≥50 ng/L; thyroid-stimulating hormone >6 mIU/L or <0.4 mIU/ L; glycated haemoglobin (HbA1c) ≥6.5%; fasting plasma glucose (FPG) ≥7.0 mmol/L; (10) Those who have difficulty swallowing, or have a condition that interferes with gastrointestinal absorption (e.g., inflammatory bowel disease, active ulcers), or have undergone gastrointestinal surgery that can lead to malabsorption, or have received long-term medications/treatments that have an effect on gastrointestinal motility [e.g., those who have undergone bariatric surgery or manipulation (e.g., gastric banding); (11) Persons with a history of hypoglycaemia prior to screening; (12) Use of any of the following medications or treatments within 12 weeks prior to screening: 1) oral or injectable hypoglycemic medications such as dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter protein-2 (SGLT-2) inhibitors, metformin, insulinotropic agents, thiazolidinediones (TZDs), and insulin, and 2) any approved or unapproved weight-loss medications (e.g., Orlistat tat, lorcaserin, phentermine/topiramate, naltrexone/bupropion, simethicone, exenatide, liraglutide, beraplatide, losenatide, tilpeptide, etc.) or weight-affecting herbal medications, health supplements, and meal replacements; and 3) use of medications that may have resulted in a significant change in body weight, including systemic (i.e., administered intravenously, orally or intra-articularly) glucocorticosteroids that lasted for more than 1 week; tricyclic antidepressants; antipsychotic or antiepileptic drugs (e.g., mipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine hydrochloride, clozapine, olanzapine, valproic acid and its derivatives, lithium, and methiheptadiazine); (13) Those who have taken any medication (including any prescription, over-the-counter, herbal and vitamin) within 2 weeks prior to screening (except those on stable antihypertensive medication); (14) Those with clinically significant abnormal 12-lead electrocardiograms (ECGs) or a QTc ≥450 ms in men and ≥470 ms in women; (15) Persons who have undergone surgery within 3 months prior to screening or who plan to undergo surgery during the trial period, and persons who have, however, undergone surgery that would interfere with the absorption, distribution, metabolism, or excretion of the drug (with the exception of surgery for appendicitis); (16) Significant changes in dietary or exercise habits within 3 months prior to screening; (17) Presence of physical deformities or disabilities that prevent accurate determination of height, weight, and other indicators; (18) A history of alcohol abuse within 3 months prior to screening [persons who consume more than 14 units of alcohol per week (1 unit ≈ 360mL of beer or 45mL of spirits of 40% alcohol by volume or 150mL of wine)]; or a positive alcohol breath study test at screening, or on admission; (19) Smoking more than 5 cigarettes per day or ingesting an equivalent amount of nicotine or nicotine replacement within 3 months prior to screening; (20) Participation in a clinical trial of any drug or medical device within 3 months prior to administration; (21) Persons who have donated or lost a significant amount of blood (≥400 mL) or have had a blood transfusion or input of blood products within 3 months prior to screening; (22) Those who do not abstain from smoking and alcohol, drinking xanthine or caffeine-containing beverages (e.g., chocolate, coffee, tea, cola, etc.), engaging in strenuous physical activity 2 days prior to dosing or during the trial period, or who have other factors that affect the absorption, distribution, metabolism, or excretion of the drug; (23) A positive urine drug screen prior to the first dose or a history of substance abuse (e.g., morphine, marijuana, methamphetamine, methylenedioxymethamphetamine, ketamine); (24) Positive Human Immunodeficiency Virus (HIV) antibody test or positive Hepatitis B Surface Antigen, Hepatitis C Antibody, or Syphilis Spirochete Antibody test at screening; (25) Those who have been vaccinated within 1 month prior to screening or plan to be vaccinated during the trial; (26) Women who are breastfeeding, and male subjects (or their partners) or female subjects who have a pregnancy plan or a sperm or egg donation plan within 30 days prior to the study and up to 6 months after the end of the study and do not wish to use effective contraception; and those who have a positive serum pregnancy test result during the screening period; (27) Those who, in the judgement of the investigator, are otherwise unsuitable for participation in this clinical trial.

研究实施时间：

Study execute time：

从 From 2024-09-20 00:00:00至 To 2027-09-20 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-09-20 00:00:00 至 To 2027-09-20 00:00:00

干预措施：

Interventions：

组别：

多次给药试验组

样本量：

 24

Group：

Experimental group

Sample size：

干预措施：

ABP2111Na片连续28天给药，依次进入ABP2111Na片50 mg、100mg和200 mg 3个剂量组（75 mg、150mg待定，可根据Ⅰa期和前期结果调整剂量）。

干预措施代码：

Intervention：

ABP2111Na tablets were administered for 28 consecutive days and sequentially entered into 3 dose groups of 50 mg, 100 mg, and 200 mg of ABP2111Na tablets (75 mg, 150 mg TBD, dose may be adjusted based on phase Ia and preliminaries results).

Intervention code：

组别：

安慰剂组

样本量：

 6

Group：

Placebo group

Sample size：

干预措施：

ABP2111Na片安慰剂连续28天给药，依次进入ABP2111Na片50 mg、100mg和200 mg 3个剂量组。

干预措施代码：

Intervention：

ABP2111Na tablets placebo was administered for 28 consecutive days and sequentially entered into 3 dose groups of ABP2111Na tablets 50 mg, 100 mg and 200 mg.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

 北京市 

Country：

China

Province：

Beijing

City：

Beijing

单位(医院)：

 北京大学人民医院 

单位级别：

 三级甲等 

Institution
hospital：

Peking University People's Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

安全性和耐受性

指标类型：

主要指标

Outcome：

Safety and tolerability

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

药代动力学（PK）特征

指标类型：

次要指标

Outcome：

Pharmacokinetic (PK) profile

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

药效动力学（PD）特征

指标类型：

次要指标

Outcome：

Pharmacodynamic (PD) profile

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

体重、腰围、臀围、BMI、腰臀比的变化。

指标类型：

次要指标

Outcome：

Changes in weight, waist circumference, hip circumference, BMI, and waist-to-hip ratio.

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

心脏安全性（浓度-QTc间期）

指标类型：

次要指标

Outcome：

Cardiac safety (concentration-QTc intervals)

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 60 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）：

本研究对每个剂量组的10例受试者按照4：1的比例随机分配到试验组和安慰剂组，将通过SAS（9.4或以上版本）采用完全随机方法进行每个剂量组中两部分受试者随机号的随机分配。

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

In this study, 10 subjects in each dose group will be randomly assigned to the test and placebo groups in a 4:1 ratio, and random assignment of random numbers to the two portions of subjects in each dose group will be carried out using a complete randomisation method via SAS (version 9.4 or above).

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：

研究者和受试者均盲

Blinding：

Investigators and subjects were blinded

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）：

预计2027年09月 临床试验公共管理平台 ResMan IPD（http://www.medresman.org.cn）

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

September 2027, ResMan IPD(http://www.medresman.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：

CRF和ResMan

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

CRF and ResMan

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2024-09-18 08:57:11