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：	ChiCTR2400083096
最近更新日期： Date of Last Refreshed on：	2024-04-16 08:54:44
注册时间： Date of Registration：	2024-04-16 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	HSK34890片在2型糖尿病患者中多次给药的安全性、耐受性、药代动力学和药效动力学的I期临床研究
Public title：	A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of HSK34890 tablets administered multiple times in patients with type 2 diabetes mellitus
注册题目简写：
English Acronym：
研究课题的正式科学名称：	HSK34890片在2型糖尿病患者中多次给药的安全性、耐受性、药代动力学和药效动力学的I期临床研究
Scientific title：	A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of HSK34890 tablets administered multiple times in patients with type 2 diabetes mellitus
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：	张炜	研究负责人：	胡伟
Applicant：	Wei Zhang	Study leader：	Hu Wei
申请注册联系人电话： Applicant telephone：	+86 551 6599 7141	研究负责人电话： Study leader's telephone：	+86 551 6599 7164
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：	zhangpharmacy@163.com	研究负责人电子邮件： Study leader's E-mail：	ayefygcp@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：	安徽省合肥市经开区芙蓉路678号	研究负责人通讯地址：	安徽省合肥市经开区芙蓉路678号
Applicant address：	678 Furong Road, ETDZ, Hefei, Anhui Province	Study leader's address：	678 Furong Road, ETDZ, Hefei, Anhui 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：	安徽医科大学第二附属医院药物临床试验中心
Applicant's institution：	Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University
研究负责人所在单位：	安徽医科大学第二附属医院药物临床试验中心
Affiliation of the Leader：	Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical 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：	YW2023-173(F1)	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：	安徽医科大学第二附属医院药物临床试验伦理委员会
Name of the ethic committee：	Ethics Committee of The Second Hospital of Anhui Medical University
伦理委员会批准日期： Date of approved by ethic committee：	2023-09-19 00:00:00
伦理委员会联系人：	张静
Contact Name of the ethic committee：	Zhang Jing
伦理委员会联系地址：	安徽省合肥市经开区芙蓉路678号
Contact Address of the ethic committee：	678 Furong Road, ETDZ, Hefei, Anhui Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 551 6380 6061	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：

安徽医科大学第二附属医院药物临床试验中心

Primary sponsor：

Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University

研究实施负责（组长）单位地址：

安徽省合肥市经开区芙蓉路678号

Primary sponsor's address：

678 Furong Road, ETDZ, Hefei, Anhui 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)：	西藏	市(区县)：
Country：	China	Province：	XIzang	City：
单位(医院)：	西藏海思科制药有限公司	具体地址：	四川省成都市温江区海峡两岸科技产业开发园百利路136号
Institution hospital：	Xizang Haisco Pharmaceutical Co., Ltd.	Address：	136 Baili Road, Cross-Strait Science and Technology Industrial Development Park, Wenjiang District, Chengdu, Sichuan Province

经费或物资来源：

西藏海思科制药有限公司

Source(s) of funding：

Xizang Haisco Pharmaceutical Co., Ltd.

研究疾病：

糖尿病

Target disease：

Diabetes

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：

I期临床试验

Study phase：

1

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

主要目的：评价HSK34890片在2型糖尿病患者中给药4周的安全性和耐受性；次要目的： 1.评价HSK34890片在2型糖尿病患者中给药4周的药代动力学特征； 2.评价HSK34890片在2型糖尿病患者中给药4周的药效动力学特征；探索性目的：评价HSK34890片在2型糖尿病患者中的剂量效应关系；

Objectives of Study：

Primary purposes: To evaluate the safety and tolerability of HSK34890 tablets administered for 4 weeks in patients with type 2 diabetes; Secondary purposes: 1. to evaluate the pharmacokinetic profile of HSK34890 tablets administered for 4 weeks in patients with type 2 diabetes mellitus; 2. to evaluate the pharmacokinetic profile of HSK34890 tablets administered for 4 weeks in patients with type 2 diabetes mellitus; Exploratory purposes: To evaluate the dose-effect relationship of HSK34890 tablets in patients with type 2 diabetes mellitus;

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. Age 18-75 years old (including 18 and 75 years old) at the time of signing the informed consent form, gender is not limited;
2. Patients with type 2 diabetes who meet the diagnostic criteria for diabetes mellitus in the Chinese Guidelines for the Prevention and Control of Type 2 Diabetes Mellitus issued by the Diabetes Branch of the Chinese Medical Association in 2020, who have undergone lifestyle intervention for at least 8 weeks prior to the screening and who have not received any glucose-lowering drug therapy;
3. Glycated hemoglobin: 7.0% ≤ HbA1c ≤ 10.5%;
4. Fasting plasma glucose < 13.9 mmol/L at screening;
5. Body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 19.0 kg/m2 and ≤ 40.0 kg/m2 at screening;
6. Agree to maintain the same dietary and exercise habits throughout the trial;
7. The subject (including the partner) has no plans to have children from the time of signing the informed consent form until 6 months after the last dose, and is willing to use the highly effective contraceptive measures specified in the protocol (see Appendix 1);
8. The subject is able to understand the procedures and methods of this trial, willing to strictly comply with the clinical research program to complete the trial, and voluntarily sign the informed consent.

排除标准：

1.非2型糖尿病：1型糖尿病、妊娠期糖尿病或其他特殊类型糖尿病； 2.筛选时存在以下任何病史或情况：（1）近6个月内有糖尿病酮症酸中毒或者高血糖高渗状态；（2）近6个月内有病情不稳定或需要治疗的增殖性视网膜病变或黄斑病变、严重糖尿病神经病变、糖尿病足或间歇性跛行；（3）近6个月内有≥ 2次严重低血糖发作病史；（4）近6个月内存在以下任何心脏疾病的病史或情况： 失代偿性心功能不全（NYHA分级为Ⅲ级或Ⅳ级）； 不稳定性心绞痛、心肌梗死、冠状动脉旁路移植术或冠脉支架植入史； 需要治疗的严重的心律失常（如长QT间期综合征等），并经研究者评估不适宜参加本临床试验；（5）筛选前未能有效控制的高血压（即筛选时收缩压（SBP）≥ 160mmHg或舒张压（DBP）≥ 100mmHg）；（6）近6个月内患有出血性脑卒中或缺血性脑卒中，并经研究者评估不适宜参加本临床试验；（7）既往有甲状腺髓样癌、多发性内分泌腺瘤病 2 型病史或家族史；（8）目前伴有未能以稳定药物剂量控制的甲状腺功能异常，且筛选时甲状腺功能检查结果存在具有临床意义的异常；（9）既往有胰腺炎病史或有症状的胆囊疾病；（10）目前患有血红蛋白病（如镰状细胞性贫血或地中海贫血、铁粒幼细胞贫血）或任何可能引起溶血或红细胞不稳定的疾病（如溶血性贫血等）；（11）既往有临床胃排空异常（如胃出口梗阻），严重慢性胃肠道疾病（如炎症性肠病、活动性溃疡）病史，或曾接受过可导致吸收不良的胃肠道手术（如减肥手术等）；（12）目前伴有严重的肾脏疾病；（13）近3个月内患有严重感染或严重外伤、或进行过重大手术，经研究者判断不适宜参加本研究；（14）近5年内具有恶性肿瘤病史（已治愈的皮肤基底细胞癌、宫颈原位癌除外），或目前正在评估潜在的恶性肿瘤；（15）存在严重精神疾患或语言障碍，不愿意或不能够充分理解和合作；（16）过去5年内有药物滥用史，包括大量反复使用与医疗目的无关的依赖性药物或物质，包括成瘾性及习惯性药物，引起身体和精神依赖性；（17）筛选前3个月内平均每日吸烟大于5支或试验期间不能停止使用任何烟草类产品者；（18）近6个月内每周饮酒超过14个标准单位，1个标准单位相当于360ml啤酒或150ml葡萄酒或45ml白酒； 3.筛选前使用了以下任何一种药物或治疗：（1）筛选前8周内曾使用过其他可能影响血糖代谢的药物，包括全身性糖皮质激素（吸入性或局部外用除外）、生长激素等；（2）筛选前8周内曾使用过具有降体重作用的药物（包括但不限于奥利司他）；（3）既往曾使用胰高血糖素样肽-1受体激动剂（GLP-1RA）；（4）在研究药物给药前14天或5个半衰期内使用CYP3A4强效抑制剂或诱导剂，或正在使用经CYP2C8/CYP2B6代谢的敏感底物，以较长时间为准。在首次给药前14天或5倍半衰期内使用P-gp抑制剂，以较长时间为准。（5）在首次研究治疗给药前7天内使用质子泵抑制剂(如奥美拉唑、埃索美拉唑、兰索拉唑、右旋兰索拉唑、泮托拉唑、雷贝拉唑等)。 4.任何实验室检查指标符合下列标准： 血红蛋白（HGB）< 10.0 g/dL（100 g/L）； 血脂肪酶和/或血淀粉酶大于正常值上限（ULN）3倍； 空腹甘油三酯（TG）> 5.7 mmol/L； 丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）> 3倍正常值上限； 总胆红素（TBIL）> 1.5倍正常值上限； 降钙素≥50 ng/L； 乙型肝炎表面抗原阳性； 抗丙型肝炎抗体阳性； 艾滋病抗体或梅毒螺旋体抗体阳性； 使用CKD-EPI公式计算的肾小球滤过率（eGFR）< 60 mL/min/1.73m2，或蛋白尿2+及以上； 5.已知对试验用药品或相关辅料过敏者； 6.筛选前3个月内入组过任何干预性药物或器械临床试验； 7.妊娠期或哺乳期妇女； 8.近3个月内献血或者失血≥ 400ml； 9.近3个月内体重变化幅度（增重或减轻）≥ 10%； 10.研究者认为不适合参加本试验的其他情况。

Exclusion criteria：

1. non-type 2 diabetes: type 1 diabetes, gestational diabetes, or other specialized types of diabetes; 2. the presence of any of the following medical history or conditions at the time of screening: (1) Diabetic ketoacidosis or hyperglycemic hyperosmolar state within the last 6 months; (2) Proliferative retinopathy or macular degeneration, severe diabetic neuropathy, diabetic foot, or intermittent claudication within the last 6 months that is unstable or requires treatment; (3) History of ≥ 2 severe hypoglycemic episodes within the last 6 months; (4) History or condition of any of the following cardiac conditions within the last 6 months:  decompensated cardiac insufficiency (NYHA class III or IV);  History of unstable angina, myocardial infarction, coronary artery bypass grafting or coronary stenting;  Serious arrhythmia requiring treatment (e.g., long QT interval syndrome, etc.) and assessed by the investigator to be inappropriate for participation in this clinical trial; (5) Hypertension that was not effectively controlled prior to screening (i.e., systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 100 mmHg at screening); (6) Hemorrhagic stroke or ischemic stroke within the last 6 months and assessed by the investigator to be unsuitable for participation in this clinical trial; (7) Previous or family history of medullary thyroid cancer, multiple endocrine adenomatosis type 2; (8) Current concomitant thyroid function abnormalities that are not controlled with stabilizing drug doses and clinically significant abnormal thyroid function test results at screening; (9) Prior history of pancreatitis or symptomatic gallbladder disease; (10) Current hemoglobinopathies (e.g., sickle cell anemia or thalassemia, ferrocytic anemia) or any condition that may cause hemolysis or red blood cell instability (e.g., hemolytic anemia, etc.); (11) Prior history of clinical gastric emptying abnormalities (e.g., gastric outlet obstruction), severe chronic gastrointestinal disease (e.g., inflammatory bowel disease, active ulcers), or previous gastrointestinal surgery that can lead to malabsorption (e.g., bariatric surgery, etc.); (12) Current concomitant severe kidney disease; (13) Suffering from a serious infection or serious trauma within the last 3 months, or having undergone major surgery, which in the judgment of the investigator makes participation in this study inappropriate; (14) Have a history of malignancy (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) within the last 5 years, or are currently being evaluated for an underlying malignancy; (15) Presence of a serious mental disorder or language barrier that makes him or her unwilling or unable to fully understand and cooperate; (16) A history of substance abuse within the past 5 years, including substantial and repeated use of dependent drugs or substances unrelated to medical purposes, including addictive and habitual drugs, causing physical and mental dependence; (17) Those who have smoked an average of greater than 5 cigarettes per day in the 3 months prior to screening or who are unable to stop using any tobacco-based products during the trial; (18) Drinking more than 14 standard units of alcohol per week in the last 6 months, with 1 standard unit equivalent to 360ml of beer or 150ml of wine or 45ml of liquor; 3. Use of any of the following medications or treatments prior to screening: (1) Use of other medications that may affect glucose metabolism, including systemic glucocorticoids (other than inhaled or topical topical), growth hormone, etc., within 8 weeks prior to screening; (2) Previous use of medications with weight-lowering effects (including but not limited to orlistat) within 8 weeks prior to screening; (3) Prior use of glucagon-like peptide-1 receptor agonists (GLP-1RA); (4) Use of a potent inhibitor or inducer of CYP3A4 or ongoing use of a sensitive substrate metabolized by CYP2C8/CYP2B6, whichever is longer, within 14 days or 5 half-lives prior to administration of study drug. Use of a P-gp inhibitor within 14 days or 5 times the half-life prior to the first dose, whichever is longer. (5) Use of a proton pump inhibitor (e.g., omeprazole, esomeprazole, lansoprazole, dextro-lansoprazole, pantoprazole, rabeprazole, etc.) within 7 days prior to the first dose of study treatment. 4. any laboratory test indicators that meet the following criteria:  Hemoglobin (HGB) < 10.0 g/dL (100 g/L);  Blood lipase and/or blood amylase greater than 3 times the upper limit of normal (ULN);  Fasting triglycerides (TG) > 5.7 mmol/L;  alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN);  Total bilirubin (TBIL) > 1.5 times upper limit of normal;  Calcitonin ≥ 50 ng/L;  Hepatitis B surface antigen positive;  Positive anti-hepatitis C antibodies;  Positive AIDS antibody or syphilis spirochete antibody;  glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 calculated using the CKD-EPI formula, or proteinuria 2+ and above; 5. Known hypersensitivity to the test drug or related excipients; 6. Enrolled in any interventional drug or device clinical trial within 3 months prior to screening; 7. Pregnant or lactating women; 8. Blood donation or blood loss of ≥ 400 ml within the last 3 months; 9. weight change (gain or loss) of ≥ 10% in the last 3 months; 10. other conditions that the investigator considers unsuitable for participation in this trial.

研究实施时间：

Study execute time：

从 From 2024-04-08 00:00:00至 To 2024-10-08 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-04-16 00:00:00 至 To 2024-10-08 00:00:00

干预措施：

Interventions：

组别：	试验组1	样本量：	9
Group：	Group 1	Sample size：	9
干预措施：	连续服用四周HSK34890片（5mg 2周；10mg 2周）	干预措施代码：
Intervention：	Four consecutive weeks of HSK34890 tablets (5 mg for 2 weeks; 10 mg for 2 weeks)	Intervention code：

组别：	试验组2	样本量：	9
Group：	Group 2	Sample size：	9
干预措施：	连续服用四周HSK34890片（10mg 2周；20mg 2周）	干预措施代码：
Intervention：	Four consecutive weeks of HSK34890 tablets (10 mg for 2 weeks; 20 mg for 2 weeks)	Intervention code：

组别：	试验组3	样本量：	9
Group：	Group 3	Sample size：	9
干预措施：	连续服用四周HSK34890片（10mg 1周；20mg 1周；40mg 2周）	干预措施代码：
Intervention：	Four consecutive weeks of HSK34890 tablets (10 mg for 1 week; 20 mg for 1 weeks; 40 mg for 2 weeks)	Intervention code：

组别：	试验组4	样本量：	9
Group：	Group 4	Sample size：	9
干预措施：	连续服用四周安慰剂	干预措施代码：
Intervention：	Four consecutive weeks of placebo	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	安徽	市(区县)：
Country：	China	Province：	Anhui	City：
单位(医院)：	安徽医科大学第二附属医院药物临床试验中心	单位级别：	三甲
Institution hospital：	Drug Clinical Trial Research Center, The Second Affiliated Hospital of Anhui Medical University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	安全结局（不良事件、生命体征、体格检查、血常规、尿常规、血液生化、凝血功能、12导联心电图）	指标类型：	主要指标
Outcome：	Safety outcome (Adverse events, vital signs, physical examination, routine blood test, urinanalysis, blood biochemistry, Coagulation function, 12-lead ECG )	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	PK指标（PK参数，PK参数与剂量间的线性关系，食物对药代动力学的影响）	指标类型：	次要指标
Outcome：	PK outcome	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	PD指标（血糖、胰岛素和体重的测量数值以及相对于基线的变化）	指标类型：	次要指标
Outcome：	PD outcome	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：

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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	75	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）：

使用区组随机化方法，将受试者按照1:1:1:1的比例随机分配至4个组别中。随机分配表由非盲统计师提供，使用SAS Enterprise Guide 8.3或以上版本统计软件包产生。

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

Using block randomization, subjects were randomly assigned to one of the four groups in a 1:1:1:1 ratio. Random assignment tables were provided by unblinded statisticians and were generated using the SAS Enterprise Guide version 8.3 or higher statistical software package.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	双盲
Blinding：	Double blinding
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	数据录入EDC系统(https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Data entry into EDC system (https://dastrial.drugchina.net/edc/home/subject/flow?siteid=1652323812354&real_siteid=1652323812354&subjectid=31&originalPage=dashboard&pageSource=visitMatrix)
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：	试验完成半年后获取研究者同意后可共享数据（http://www.medresman.org.cn/login.aspx）
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data can be shared after obtaining investigator consent in six months after trial completion (http://www.medresman.org.cn/login.aspx)
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：	2024-04-16 08:54:30