ChiCTR2400086200 版本V1.0 版本创建时间2024/06/26 17:13:39 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：

ChiCTR2400086200 

最近更新日期：

Date of Last Refreshed on：

2024-06-26 17:13:34 

注册时间：

Date of Registration：

2024-06-26 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

评价注射用辅酶I在健康受试者中单次、多次剂量递增的安全性、耐受性和药代动力学的随机、双盲、安慰剂对照的I期临床研究

Public title：

A randomized, double-blind, placebo-controlled phase I clinical study evaluating the safety, tolerability, and pharmacokinetics of single and multiple dose escalation of coenzyme I for injection in healthy subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评价注射用辅酶I在健康受试者中单次、多次剂量递增的安全性、耐受性和药代动力学的随机、双盲、安慰剂对照的I期临床研究

Scientific title：

A randomized, double-blind, placebo-controlled phase I clinical study evaluating the safety, tolerability, and pharmacokinetics of single and multiple dose escalation of coenzyme I for injection in 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：

王康林 

研究负责人：

马礼坤 

Applicant：

Kanglin Wang 

Study leader：

Likun Ma 

申请注册联系人电话：

Applicant telephone：

+86 130 8308 9180

研究负责人电话：

Study leader's telephone：

+86 187 5696 7633

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：

wangkanglin@knb-pharma.com

研究负责人电子邮件：

Study leader's E-mail：

lkma119@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：

安徽省合肥市长丰县双凤开发区双凤智谷4号科技楼

研究负责人通讯地址：

安徽省合肥市庐阳区庐江路17号

Applicant address：

Science and Technology Building, No. 4 Shuangfeng Zhigu, Shuangfeng Development Zone, Changfeng County, Hefei City, Anhui Province

Study leader's address：

No. 17 Lujiang Road, Luyang District, Hefei City, 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：

康诺生物制药股份有限公司

Applicant's institution：

Knature Biopharmaceutical Co., Ltd

研究负责人所在单位：

中国科学技术大学附属第一医院

Affiliation of the Leader：

The First Affiliated Hospital of University of Science and Technology of China

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：

2023伦审248号; 2023伦审387号; 2023伦审569号; 2023伦审752号

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：

中国科学技术大学附属第一医院医学研究伦理委员会

Name of the ethic committee：

Medical Research Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China

伦理委员会批准日期：

Date of approved by ethic committee：

2023-04-26 00:00:00

伦理委员会联系人：

沈佐君

Contact Name of the ethic committee：

Zuojun Shen

伦理委员会联系地址：

安徽省合肥市庐江路17号安徽省立医院行政楼六楼

Contact Address of the ethic committee：

6th Floor, Administrative Building, Anhui Provincial Hospital, No. 17 Lujiang Road, Hefei City, Anhui Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 551 6228 2931

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：

中国科学技术大学附属第一医院

Primary sponsor：

The First Affiliated Hospital of University of Science and Technology of China

研究实施负责（组长）单位地址：

安徽省合肥市庐阳区庐江路17号

Primary sponsor's address：

No. 17 Lujiang Road, Luyang District, Hefei City, 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)：

安徽

市(区县)：

合肥

Country：

China

Province：

Anhui

City：

Hefei

单位(医院)：

中国科学技术大学附属第一医院

具体地址：

安徽省合肥市庐阳区庐江路17号

Institution
hospital：

The First Affiliated Hospital of University of Science and Technology of China

Address：

No. 17 Lujiang Road, Luyang District, Hefei City, Anhui Province

经费或物资来源：

康诺生物制药股份有限公司

Source(s) of funding：

Knature Biopharmaceutical 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：

 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：

主要研究目的：评估中国健康成年受试者单次和多次静脉给药不同剂量辅酶Ⅰ后的安全性、耐受性。 次要研究目的：评估中国健康成年受试者单次和多次静脉给药不同剂量辅酶Ⅰ后的PK特征。  

Objectives of Study：

Main research purpose:To evaluate the safety and tolerability of different doses of coenzyme I after single and multiple intravenous administration in healthy Chinese adult subjects. Secondary research objectives:To evaluate the PK characteristics of Chinese healthy adult subjects after single and multiple intravenous administration of different doses of coenzyme I.

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．年龄为18~60岁（包含临界值，以签署知情同意书时间为准）的健康成年男性或女性受试者； 2．体重指数（BMI）为18~26 kg/m2（包括临界值），男性受试者体重不得低于50?kg，女性受试者体重不得低于45 kg； 3．有生育能力的合格受试者（男性或女性）必须同意在试验期间和末次给药后3个月内采用一种经医学认可的非药物避孕措施（如宫内节育器或避孕套）；不具有生育能力的女性，指经外科手术绝育（至少在筛选前6周进行了子宫切除术/双侧输卵管切除术/双侧卵巢切除术）或已绝经（已绝经定义为已12个月无月经，无其他医学原因）； 4．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，自愿作为受试者，并签署知情同意书； 5．能够按照方案要求完成试验者。

Inclusion criteria

1. Healthy adult male or female subjects aged 18-60 years (including the threshold value, based on the time of signing the informed consent); 2. A body mass index (BMI) of 18 to 26 kg/m2 (including the cut-off), with a weight of not less than 50 kg for male subjects and not less than 45 kg for female subjects; 3. Eligible subjects (male or female) who are fertile must consent to the use of a medically approved non-drug contraceptive (such as an IUD or condom) during the trial period and for 3 months after the final dose; Women who are not fertile, are surgically sterilized (hysterectomy/bilateral salpingectomy/bilateral oophorectomy at least 6 weeks prior to screening) or have gone through menopause (defined as having gone 12 months without menstruation without other medical reasons); 4. Subjects fully understand the purpose, nature, method and possible adverse reactions of the test, voluntarily act as subjects, and sign informed consent; 5. Able to complete the test according to the requirements of the scheme.

排除标准：

1.过敏性体质或怀疑对试验用药品中的任何成分过敏者； 2.受试者既往病史异常有临床意义或其他发现异常有临床意义的疾病或因素，包括但不限于神经、心血管、血液、肝脏、肾脏、胃肠道、呼吸、代谢、内分泌、免疫、骨骼系统疾病或其他因素； 3.筛选期体格检查、生命体征、心脏彩超、腹部彩超、实验室检查（血常规、血生化、尿常规等）、12导联心电图（ECG）、胸部正侧位片等检查结果异常，并且经研究者判断异常有临床意义者。包括女性受试者的QTcF> 470 ms，男性受试者的QTcF> 450?ms（经Fridericia公式校正）；心脏彩超射血分数< 55%，或者心脏彩超发现有临床意义的心脏结构性异常或瓣膜异常； 4.筛选前30天内发生过严重感染或筛选前7天内存在感染症状，包括急慢性感染以及局部感染（细菌、病毒、寄生虫、真菌或其他机会性感染病原体），且经研究者判断不适合参加者； 5.有慢性肝/胆疾病病史，或既往三个月内出现过肝酶升高或肝功能异常且经研究者判定异常有临床意义者，或筛选期/基线期肝功能异常[肝功能指标：丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）或总胆红素> 正常上限（ULN）]（对于单纯性脂肪肝且肝功能指标正常受试者可以纳入）； 6.筛选期肾小球滤过率（eGFR）< 90 mL/min/1.73m2者； 7.筛选前3个月内接受过重大外科手术或发生骨折，或在试验期间预期需要进行手术者； 8.经研究者判断，静脉采血有困难者； 9.筛选前2年内曾有过药物滥用史或筛选前3个月使用过毒品，或筛选期药物滥用筛查阳性者； 10.筛选前3个月内每日吸烟量大于5支或习惯性使用含尼古丁制品者； 11.筛选前6个月内每周饮酒量大于14单位酒精（1单位酒精=360 mL啤酒或45?mL酒精含量为40%的烈酒或150 mL葡萄酒）或给药前48 h服用过含酒精的制品，或筛选期和/或基线期酒精呼气测试阳性者； 12.试验开始给药前14天内（或药物5个半衰期内，以更长者为准）使用过任何处方药（包括诱导和抑制肝药酶的药物）、非处方药、中草药、维生素或保健品者； 13.筛选前7天内食用含有高含量NAD+、烟酰胺核苷（NR）或NAM及烟酸相关成分的食品或药品者，包括乳制品、维生素B3和天然保健品； 14.试验开始给药前7天内服用过含有可诱导或抑制肝脏代谢酶的食物或饮料（如西柚等）者； 15.在给药前48 h内摄取了任何含有或代谢后产生咖啡因或黄嘌呤食物或饮料（如咖啡、茶、巧克力），特殊饮食（包括火龙果、芒果、柚子等）或有剧烈运动，或其他影响药物吸收、分布、代谢、排泄等因素者； 16.人类免疫缺陷病毒（HIV）抗体、乙肝表面抗原或E抗原、丙肝抗体、梅毒螺旋体抗体，任一项阳性者； 17.筛选期或基线期妊娠试验阳性或处于哺乳期的妇女； 18.在首次使用试验用药品前3个月内接受过任何其他试验用药品给药或医疗器械临床试验者； 19.在筛选前3个月有献血史或失血超过400 mL者（不包括女性生理期失血），或计划在研究期间或研究结束后1个月内献血者； 20.筛选前1个月内接种过或计划在研究期间或研究结束后1个月内接种活疫苗或减毒疫苗者； 21.从筛选期至研究用药前发生急性疾病或有伴随用药者； 22.在筛选前5年内有恶性肿瘤史者（不包括已切除的非黑色素瘤皮肤癌）； 23.不能遵守统一饮食与活动管理者； 24.其他任何研究者认为可能影响受试者提供知情同意或遵循试验方案的情况，或受试者参加试验可能影响试验结果或自身安全的情况。

Exclusion criteria：

1. Persons with allergic constitution or suspected allergy to any component of the investigational drug; 2. Diseases or factors with clinical significance or other abnormal clinical significance, including but not limited to neurological, cardiovascular, blood, liver, kidney, gastrointestinal, respiratory, metabolic, endocrine, immune, skeletal system diseases or other factors; 3. Patients with abnormal results of physical examination, vital signs, heart color Doppler ultrasound, abdominal color Doppler ultrasound, laboratory examination (blood routine, blood biochemistry, urine routine, etc.), 12-lead electrocardiogram (ECG), chest anterior-lateral radiography, etc. during the screening period, and who were judged by researchers to be clinically significant. Included QTcF> 470 ms for female subjects and QTcF> 450 ms for male subjects (corrected by Fridericia's formula); Cardiac ultrasound ejection fraction < 55%, or the cardiac ultrasound found clinically significant cardiac structural or valve abnormalities; 4. Severe infection within 30 days prior to screening or symptoms of infection within 7 days prior to screening, including acute and chronic infections as well as local infections (bacterial, viral, parasitic, fungal, or other opportunistic pathogens), which are judged by the investigator to be unsuitable for participants; 5. Patients with a history of chronic liver/bile disease, or who have experienced elevated liver enzymes or abnormal liver function within the past three months and have been determined by the investigators to be clinically significant, or abnormal liver function during the screening period/baseline period [Liver function indicators: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin > upper limit of normal (ULN)] (subjects with simple fatty liver disease and normal liver function indicators can be included); 6. Patients with glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 during the screening period; 7. Patients who have undergone major surgical operations or fractures in the 3 months prior to screening, or who are expected to require surgery during the trial period; 8. Patients with difficulty in venous blood collection judged by the researchers; 9. Had a history of drug abuse within 2 years prior to screening or had used drugs within 3 months prior to screening, or had tested positive for drug abuse during the screening period; 10. Those who smoked more than 5 cigarettes a day or habitually used nicotine-containing products in the 3 months before screening; 11. Persons who consumed more than 14 units of alcohol per week in the six months prior to screening (1 unit of alcohol =360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine) or had consumed alcoholic products in the 48 hours prior to administration, or had a positive alcohol breath test during screening and/or baseline; 12. Use of any prescription drugs (including drugs that induce and inhibit liver drug enzymes), over-the-counter medicines, Chinese herbs, vitamins, or health supplements within 14 days prior to the start of the trial (or within 5 half-lives of the drug, whichever is older); 13. Food or pharmaceutical products containing high levels of NAD+, niacinamide riboside (NR) or NAM and niacin related ingredients, including dairy products, vitamin B3 and natural health products, in the 7 days prior to screening; 14. People who have taken food or drink (such as grapefruit, etc.) containing enzymes that can induce or inhibit liver metabolism within 7 days before the start of the trial; 15. Ingested any food or drink containing or metabolizing caffeine or xanthine (such as coffee, tea, chocolate), special diet (including dragon fruit, mango, grapefruit, etc.) or had strenuous exercise, or other factors affecting drug absorption, distribution, metabolism, excretion, etc.; 16. Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen or E antigen, hepatitis C antibody, treponema pallidum antibody, any one of the positive; 17. Women who have positive pregnancy tests during the screening or baseline period or who are breastfeeding; 18. Persons who have received any other investigational drug administration or clinical trial of a medical device within 3 months prior to the first use of the investigational drug; 19. People with a history of blood donation or blood loss exceeding 400 mL in the 3 months prior to screening (excluding menstrual blood loss in women), or who plan to donate blood during the study period or within 1 month after the end of the study; 20. Persons who have received live or attenuated vaccines within 1 month prior to screening or plan to receive live or attenuated vaccines during the study period or within 1 month after the end of the study; 21. Acute illness or concomitant drug use occurred from the screening period to the study drug use; 22. A history of malignancy within 5 years prior to screening (excluding excised non-melanoma skin cancer); 23. Failure to comply with unified diet and activity management; 24. Any other circumstances that the investigator believes may affect the subject's provision of informed consent or adherence to the protocol of the test, or the subject's participation in the test may affect the test results or his or her own safety.

研究实施时间：

Study execute time：

从 From 2023-06-13 00:00:00至 To 2024-02-29 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-06-13 00:00:00 至 To 2024-02-19 00:00:00  

干预措施：

Interventions：

组别：

基线水平探索组

样本量：

2

Group：

Baseline level exploration group

Sample size：

干预措施：

无

干预措施代码：

Intervention：

NA

Intervention code：

组别：

单次给药研究-剂量组1-试验组

样本量：

6

Group：

Single Dose Administration Study - Dose Group 1- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 50mg

干预措施代码：

Intervention：

50mg of coenzyme I intravenously

Intervention code：

组别：

单次给药研究-剂量组2-试验组

样本量：

8

Group：

Single Dose Administration Study - Dose Group 2- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 100mg

干预措施代码：

Intervention：

received intravenous coenzyme I 100mg

Intervention code：

组别：

单次给药研究-剂量组3-试验组

样本量：

8

Group：

Single Dose Administration Study - Dose Group 3- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 200mg

干预措施代码：

Intervention：

received 200mg of coenzyme I intravenously

Intervention code：

组别：

单次给药研究-剂量组4-试验组

样本量：

8

Group：

Single Dose Administration Study - Dose Group 4- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 400mg

干预措施代码：

Intervention：

received intravenous coenzyme I 400mg

Intervention code：

组别：

单次给药研究-剂量组5-试验组

样本量：

8

Group：

Single Dose Administration Study - Dose Group 5- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 600mg

干预措施代码：

Intervention：

received intravenous coenzyme I 600mg

Intervention code：

组别：

单次给药研究-剂量组6-试验组

样本量：

8

Group：

Single Dose Administration Study - Dose Group 6- experimental group

Sample size：

干预措施：

静脉输注辅酶 I 800mg

干预措施代码：

Intervention：

received intravenous coenzyme I infusion of 800mg

Intervention code：

组别：

多次给药研究-剂量组1-试验组

样本量：

8

Group：

Multiple Dosing Study - Dose Group 1- experimental group

Sample size：

干预措施：

连续5天，每天静脉输注辅酶 I 200mg

干预措施代码：

Intervention：

For 5 consecutive days, received a daily intravenous infusion of coenzyme I 200mg

Intervention code：

组别：

多次给药研究-剂量组2-试验组

样本量：

8

Group：

Multiple Dosing Study - Dose Group 2- experimental group

Sample size：

干预措施：

连续5天，每天静脉输注辅酶 I 500mg

干预措施代码：

Intervention：

For 5 consecutive days, received an intravenous infusion of 500mg coenzyme I daily

Intervention code：

组别：

单次给药研究-剂量组1-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 1- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

单次给药研究-剂量组2-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 2- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

单次给药研究-剂量组3-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 3- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

单次给药研究-剂量组4-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 4- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

单次给药研究-剂量组5-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 5- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

单次给药研究-剂量组6-对照组

样本量：

2

Group：

Single Dose Administration Study - Dose Group 6- control group

Sample size：

干预措施：

接受安慰剂

干预措施代码：

Intervention：

received placebo

Intervention code：

组别：

多次给药研究-剂量组1-对照组

样本量：

2

Group：

Multiple Dosing Study - Dose Group 1- control group

Sample size：

干预措施：

连续5天，接受安慰剂。

干预措施代码：

Intervention：

For 5 consecutive days, received placebo.

Intervention code：

组别：

多次给药研究-剂量组2-对照组

样本量：

2

Group：

Multiple Dosing Study - Dose Group 2- control group

Sample size：

干预措施：

连续5天，接受安慰剂。

干预措施代码：

Intervention：

For 5 consecutive days, received 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)：

 合肥 

Country：

China 

Province：

Anhui 

City：

Hefei 

单位(医院)：

中国科学技术大学附属第一医院 

单位级别：

三甲 

Institution
hospital：

The First Affiliated Hospital of University of Science and Technology of China

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

耐受性/安全性评价指标：AE 的发生率和严重程度；SAE 发生率和 SUSAR；实验室检查（血常规、血生化、心肌酶谱、尿常规、凝血功能检查等）；12 导联 ECG；生命体征；体格检查。

指标类型：

主要指标

Outcome：

Tolerance/safety evaluation indicators: incidence and severity of adverse events (AE); SAE incidence and SUSAR; Laboratory tests (blood routine, blood biochemistry, myocardial enzyme spectrum, urine routine, coagulation function test, etc.); 12 lead ECG; Vital signs; Physical examination.

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

SAD 研究的 PK 参数主要包括：原形和代谢物的血药浓度达峰时间（Tmax）、Cmax、AUC0-t、AUC0-∞、消除半衰期（t1/2，如适用）等

指标类型：

次要指标

Outcome：

The PK parameters of SAD research mainly include: peak time (Tmax) of blood drug concentration of prototype and metabolites, Cmax, AUC0-t, AUC0-∞, Elimination of half-life (t1/2, if applicable), 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：

MAD 研究的 PK 参数主要包括：原形和代谢物的稳态达峰时间（Tss,max）、稳态最大血药浓度（Css,max）、稳态谷浓度（Ctrough）、稳态平均血药浓度（Css,avg）、稳态药物浓度-时间曲线下面积（AUC0-τ）、t1/2（如适用）、AUC0-τ的蓄积比（Rac_AUC）、Cmax的蓄积比（Rac_Cmax）、尿液的累积排泄量（Ae）等。

指标类型：

次要指标

Outcome：

The PK parameters of MAD research mainly include: steady-state peak time (Tss, max) of the prototype and metabolites, steady-state maximum blood drug concentration (Css, max), steady-state trough concentration (Ctrough), steady-state average blood drug concentration (Css, avg), area under the steady-state drug concentration time curve (AUC0- τ), t1/2 (if applicable), AUC0- τ accumulation ratio (Rac-AUC), Cmax accumulation ratio (Rac-Cmax), cumulative excretion of urine (Ae), etc.

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：

结束

/Completed

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）：

本试验采用区组随机化方法，每一剂量组单独随机。每例受试者接受试验药物或安慰剂将由随机表确定，随机表由统计单位应用SAS（9.4或以上版本）产生。在筛选时，每例受试者将使用筛选号进行识别，按照签署知情同意书的先后顺序依次给予筛选号，筛选号从001开始，依次编写。随机化在给药前2日进行。每一剂量组单独随机，单次给药研究受试者随机号编号原则如下：基线水平探索，S0001-S0002，第1剂量组，S0101-S0108，第2剂量组：S0201-S0210，以此类推。多次给药研究受试者随机号编号原则如下：第1剂量组：M0101-M0110，第2剂量组：M0201-M0210。获得随机号至PK基线样本采集前，受试者由于任何原因脱落造成不能采集PK基线样本的，采用试验前符合入组标准但未入组的受试者进行替补，替补的受试者随机号在脱落的受试者随机号上+1000，替补的受试者与脱落的受试者药物编号保持一致。对于在PK基线样本采集后和给药后脱落的受试者，经研究者和申办方共同讨论是否补充受试者，在PK基线样本采集后且在给药前脱落的受试者，替补的受试者与脱落的受试者药物编号保持一致，在给药后脱落的受试者，替补的受试者使用脱落的受试者备用试验用药品。

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

Block randomization was used in this study, with each dose group randomized individually. Each subject receiving the trial drug or placebo will be determined by a randomization table generated by the statistical unit applying SAS (version 9.4 or above). In the screening process, each subject will be identified with a screening number, which will be given in sequence according to the order in which the informed consent is signed. The screening number will be written in sequence starting from 001. Randomization was performed 2 days before administration. Each dose group was randomized individually, and the randomization of participants in the single dose study was as follows: baseline level exploration, S0001-S0002, first dose group, S0101-S0108, second dose group, S0201-S0210, and so on. The randomized number of participants in multiple dose studies is as follows: first dose group: M0101-M0110, second dose group: M0201-M0210. If the PK baseline sample cannot be collected due to any reason that the subject falls off, the subjects who meet the enrollment criteria before the trial but are not enrolled will be replaced. The replacement subject's random number will be +1000 on the dropped subject's random number, and the replacement subject's drug number will be consistent with the dropped subject's drug number. For subjects who drop off after PK baseline sample collection and after administration, the investigator and sponsor will discuss whether to supplement subjects. For subjects who drop off after PK baseline sample collection and before administration, the drug number of the replacement subjects will be consistent with the drug number of the dropped subjects. For subjects who drop off after administration, the replacement subjects will use the experimental drug of the dropped subjects.

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：

本次研究采用双盲设计，除非盲人员（如：非盲药品管理员、非盲研究护士等）外，其他研究团队人员和受试者均不知道使用的是何种药物。由申办者或其指定的单位提供试验药物和安慰剂，安慰剂和试验药物的外包装和标签均保持一致，以确保盲态。盲底在研究期间必须始终置于安全地方直至研究完成，防止被其他执行临床研究的人员知悉。如果出现医学急救，管理受试者状况而需要了解受试者使用的是试验药物还是安慰剂时，可由主要研究者（PI）授权的人员打开该受试者密封的应急信件，如有可能，出现此类紧急情况时，在揭露对受试者的分配药物之前，应与研究监查员和申办者医学代表先进行讨论。电子病例报告表（eCRF）中必须清晰合理阐述及证明破盲的理由，破盲日期以及负责人员的ID同样必须记录。除准备试验用药品的人员、准备随机列表的统计师、研究中配备的非盲人员，以及出现需要揭盲的医疗事件，所有临床和非临床人员均将对治疗分配保持盲态直至揭盲。

Blinding：

This study adopted a double-blind design, except for blind personnel (such as non-blind drug administrators, non-blind study nurses, etc.), other research team members and subjects did not know which drugs were used. The sponsor or its designated unit provides the experimental drug and placebo, and the outer packaging and labeling of the placebo and the experimental drug are consistent to ensure blind status. The blind floor must be kept in a safe place at all times during the study period until the study is completed to prevent it from being known to other persons conducting the clinical study. In the event of a medical emergency in which it is necessary to manage the subject's condition to know whether the subject is on the trial drug or placebo, the subject's sealed emergency letter may be opened by a person authorized by the Principal Investigator (PI) and, if possible, discussed with the study monitor and sponsor's medical representative before disclosing the subject's drug assignment in such an emergency. The reason for breaking the blindness must be clearly and reasonably stated in the electronic Case Report form (eCRF), and the date of breaking the blindness and the ID of the person responsible must also be recorded. Except for personnel preparing investigational drugs, statisticians preparing randomized lists, non-blind personnel assigned to the study, and medical events requiring unblinds, all clinical and non-clinical personnel will remain blind on treatment assignment until unblinds are revealed.

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）：

https://dastrial.drugchina.net/login

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

https://dastrial.drugchina.net/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：

本研究将采用电子数据采集（EDC）系统采集数据。电子病例报告表由研究者或者研究者指定人员（需在研究授权表中注明）依据源文件（原始病历、检查报告单等）填写，需确保信息的完整性和准确性。EDC系统将自动保留数据的稽查轨迹，包括数据录入和更改的时间、操作人、更改原因、更改前数据值、更改后数据值等，以保证数据的可溯源性。

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

This study will use an electronic data capture (EDC) system to capture data. The electronic case report form will be completed by the investigator or the investigator's designee (to be indicated in the study authorisation form) based on the source documents (original medical records, examination report forms, etc.), and the completeness and accuracy of the information needs to be ensured.The EDC system will automatically keep an audit trail of the data, including the time of data entry and change, operator, reason for the change, the data value before the change, and the data value after the change, etc., in order to ensure the traceability of the data.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-06-26 17:13:34