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：	ChiCTR2500113821
最近更新日期： Date of Last Refreshed on：	2025-12-03 15:37:41
注册时间： Date of Registration：	2025-12-03 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	评估113口服冻干粉在中国健康成年受试者中单次和多次给药的安全性以及药代动力学特征的I期临床研究
Public title：	Phase I Clinical Study to Evaluate the Safety and Pharmacokinetic Profile of Oral Lyophilized Powder of 113 in Healthy Chinese Adult Subjects Following Single and Multiple Doses
注册题目简写：
English Acronym：
研究课题的正式科学名称：	评估113口服冻干粉在中国健康成年受试者中单次和多次给药的安全性以及药代动力学特征的I期临床研究
Scientific title：	Phase I Clinical Study to Evaluate the Safety and Pharmacokinetic Profile of Oral Lyophilized Powder of 113 in Healthy Chinese Adult Subjects Following Single and Multiple Doses
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：	黄洁	研究负责人：	阳国平
Applicant：	Huang Jie	Study leader：	Yang Guoping
申请注册联系人电话： Applicant telephone：	+86 731 8991 8665	研究负责人电话： Study leader's telephone：	+86 731 8991 8938
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：	cellahuang1988@163.com	研究负责人电子邮件： Study leader's E-mail：	ygp9880@126.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：	中国湖南省长沙市岳麓区桐梓坡路138号	研究负责人通讯地址：	中国湖南省长沙市岳麓区桐梓坡路138号
Applicant address：	No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, China	Study leader's address：	No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, 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：	中南大学湘雅三医院临床试验研究中心
Applicant's institution：	Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University
研究负责人所在单位：	中南大学湘雅三医院临床试验研究中心
Affiliation of the Leader：	Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South 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：	25182	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：	中南大学湘雅三医院伦理委员会
Name of the ethic committee：	The Ethics Committee of the Third Xiangya Hospital of Central South University
伦理委员会批准日期： Date of approved by ethic committee：	2025-10-23 00:00:00
伦理委员会联系人：	王晓敏
Contact Name of the ethic committee：	xiaomin Wang
伦理委员会联系地址：	中国湖南省长沙市岳麓区桐梓坡路138号中南大学湘雅三医院伦理委员会
Contact Address of the ethic committee：	Ethics Committee of the Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha City, Hunan Province, China
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 731 8861 8938	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：

中南大学湘雅三医院临床试验研究中心

Primary sponsor：

Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University

研究实施负责（组长）单位地址：

中国湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

Changsha City, Hunan Province, 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)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	中南大学湘雅三医院	具体地址：	中国湖南省长沙市岳麓区桐梓坡路138号
Institution hospital：	the Third Xiangya Hospital, Central South University	Address：	Changsha City, Hunan Province, China

经费或物资来源：

广州南新制药有限公司

Source(s) of funding：

Guangzhou Nanxin Pharmaceutical Co., Ltd.

研究疾病：

急性缺血性脑卒

Target disease：

Acute Ischemic Stroke (AIS)

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：

随机交叉对照

Study design：

Cross-over

研究目的：

1.考察健康受试者单次及多次给予不同剂量水平的113口服冻干粉后的安全性、耐受性； 2.考察健康受试者给予113口服冻干粉、丁苯酞软胶囊、丁苯酞氯化钠注射液三种不同制剂后体内丁苯酞的药动学特征，评价113口服冻干粉的生物利用度； 3.考察健康受试者单次及多次给予不同剂量水平的113口服冻干粉后体内药动学特征； 4.通过建立模型外推113口服冻干粉的临床给药剂量。

Objectives of Study：

1.To investigate the safety and tolerability of 113 Oral Lyophilized Powder in healthy subjects after single and multiple administrations at different dose levels; 2.To investigate the pharmacokinetic characteristics of butylphthalide in vivo in healthy subjects following the administration of three different formulations (113 Oral Lyophilized Powder, Butylphthalide Soft Capsules, and Butylphthalide Sodium Chloride Injection), and to evaluate the bioavailability of 113 Oral Lyophilized Powder; 3.To investigate the in vivo pharmacokinetic characteristics of 113 Oral Lyophilized Powder in healthy subjects after single and multiple administrations at different dose levels; 4.To extrapolate the clinical administration dose of 113 Oral Lyophilized Powder by establishing a model.

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.经病史询问、体格检查、生命体征检查（血压、体温、脉率）及血常规、血生化、尿常规、12-导联心电图、凝血功能、乙肝表面抗原（HBs-Ag）、人免疫缺陷病毒抗原抗体、丙型肝炎抗体和梅毒螺旋体抗体等检查异常且具有临床意义者； 2.（筛选期/入住问诊）有严重出血倾向疾病史者； 3.（筛选期/入住问诊）有心、肝、肾、内分泌、消化道、血液系统、呼吸系统、免疫系统、神经系统精神疾病严重病史或慢性病病史或现有上述系统疾病者； 4.（筛选期/入住问诊）入住前两周内曾使用过任何药物（包括处方药、非处方药、维生素补充剂或中草药）、保健品者； 5.（筛选期/入住问诊）入住前2周内接种疫苗或试验期间计划接种疫苗者； 6.（筛选期问诊）已知对芹菜、丁苯酞及其辅料过敏者，或对其他药物或食物过敏者； 7.（筛选期/入住问诊）既往有药物滥用史或一年内使用过毒品者； 8.（筛选期/入住问诊）试验首次给药前3个月内平均每日吸烟量多于5支，或试验期间不能停止使用任何烟草类产品者（含尼古丁制品）； 9.（筛选期/入住问诊）试验首次给药前6个月内经常饮酒者，即每周饮酒超过14单位酒精（1单位等于17.5ml或14g纯酒精，不同品种酒类酒精含量以体积比标示，1个酒精单位约等于50°白酒35ml或5°啤酒350ml），或整个试验期间不愿意停止饮酒或食用任何含酒精的制品者； 10.（筛选期/入住问诊+联网筛查）入住前3个月内参加过任何药物临床试验并使用了试验药物者； 11.（筛选期/入住问诊）入住前6个月内接受过任何外科手术或试验期间计划手术者； 12.（筛选期问诊）不能接受静脉穿刺，有晕针晕血史者； 13.（筛选期/入住问诊）入住前3个月内献血或失血400ml及以上者或计划在研究期间献血或血液成分者； 14.（筛选期/入住问诊）入住前3个月内每天饮用过量茶、咖啡或含咖啡因的饮料（8杯以上，1杯=250ml）者； 15.（筛选期/入住问诊）在首次服用研究药物前48小时内，吃过葡萄柚等影响代谢酶的水果或相关食品；或摄取了任何含咖啡因或富含黄嘌呤成分的食物或饮料（如咖啡、浓茶、巧克力、可乐等）者；或者首次服用研究药物前1周内食用过芹菜类（旱芹、西芹等）食物或者产品。 16.（筛选期/入住问诊）给药前30天内使用过任何改变肝酶活性的药物（如：诱导剂—巴比妥类、卡马西平、苯妥英、糖皮质激素；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、镇静催眠药、维拉帕米、氟喹诺酮类、抗组胺类、奥美拉唑）者；不同意在试验期间避免食用影响代谢酶的水果（例如葡萄柚）或相关产品以及烟酒或含咖啡因的饮料、以及芹菜类（旱芹、西芹等）食物，或避免剧烈运动者； 17.酒精呼气测试结果大于0mg/100ml，尿液多项毒品联合检测呈阳性； 18.（筛选期/入住问诊）妊娠检查阳性或处于哺乳期的女性受试者；筛选前2周内有无保护措施的性行为的女性受试者。试验首次给药前30天内使用口服避孕药，或试验首次给药前6个月内使用过长效雌激素或孕激素注射剂或埋植片者； 19.（筛选期/入住问诊）男性受试者（或其伴侣）或女性受试者自签署知情同意书开始3个月内有生育计划，或不能或不愿意按照研究者的指导在研究期间采取研究者认可的避孕措施者； 20.（筛选期问诊）不能遵守统一饮食者； 21.（筛选期问诊）吞咽功能障碍者； 22.受试者依从性不佳或因个人原因无法遵守研究方案的相关规定，研究者判断不适合参加本临床研究的受试者。

Exclusion criteria：

1.Subjects with clinically significant abnormalities identified through medical history inquiry, physical examination, vital sign measurements (blood pressure, body temperature, pulse rate), as well as tests including routine blood tests, blood biochemistry, routine urine tests, 12-lead electrocardiogram (ECG), coagulation function, hepatitis B surface antigen (HBs-Ag), human immunodeficiency virus (HIV) antigen-antibody, hepatitis C virus (HCV) antibody, and Treponema pallidum antibody; 2.(Screening period/admission interview) Subjects with a history of diseases associated with a severe bleeding tendency; 3.(Screening period/admission interview) Subjects with a history of severe diseases or chronic diseases involving the heart, liver, kidneys, endocrine system, digestive system, hematological system, respiratory system, immune system, or nervous/psychiatric system, or current diseases affecting any of these systems; 4.(Screening period/admission interview) Subjects who have used any medications (including prescription drugs, over-the-counter drugs, vitamin supplements, or Chinese herbal medicines) or health supplements within two weeks prior to admission; 5.(Screening period/admission interview) Subjects who have received a vaccine within two weeks prior to admission or plan to receive a vaccine during the trial period; 6.(Screening period interview) Subjects with a known allergy to celery, butylphthalide, or their excipients, or allergies to other drugs or foods; 7.(Screening period/admission interview) Subjects with a history of drug abuse or who have used illegal drugs within one year; 8.(Screening period/admission interview) Subjects who smoked an average of more than 5 cigarettes per day within 3 months prior to the first administration of the trial drug, or who cannot refrain from using any tobacco products (including nicotine-containing products) during the trial period; 9.(Screening period/admission interview) Subjects with a history of regular alcohol consumption within 6 months prior to the first administration of the trial drug, i.e., consuming more than 14 units of alcohol per week (1 unit equals 17.5 ml or 14 g of pure alcohol; the alcohol content of different types of alcoholic beverages is indicated by volume ratio, and 1 alcohol unit is approximately equivalent to 35 ml of 50% alcohol by volume (ABV) Chinese liquor or 350 ml of 5% ABV beer), or who are unwilling to abstain from alcohol or any alcohol-containing products throughout the trial period; 10.(Screening period/admission interview + online screening) Subjects who have participated in any drug clinical trial and used the trial drug within 3 months prior to admission; 11.(Screening period/admission interview) Subjects who have undergone any surgical operation within 6 months prior to admission or plan to undergo surgery during the trial period; 12.(Screening period interview) Subjects who cannot tolerate venipuncture or have a history of fainting due to needle pricks or blood; 13.(Screening period/admission interview) Subjects who have donated blood or lost 400 ml or more of blood within 3 months prior to admission, or plan to donate blood or blood components during the study period; 14.(Screening period/admission interview) Subjects who have consumed excessive amounts of tea, coffee, or caffeinated beverages (more than 8 cups per day, with 1 cup = 250 ml) within 3 months prior to admission; 15.(Screening period/admission interview) Subjects who have consumed fruits or related foods that affect metabolic enzymes (e.g., grapefruit) within 48 hours prior to the first administration of the study drug; or have ingested any foods or beverages containing caffeine or rich in xanthine (such as coffee, strong tea, chocolate, cola, etc.); or have consumed celery-related foods or products (e.g., Chinese celery, western celery) within 1 week prior to the first administration of the study drug; 16.(Screening period/admission interview) Subjects who have used any drugs that alter liver enzyme activity within 30 days prior to drug administration (e.g., inducers—barbiturates, carbamazepine, phenytoin, glucocorticoids; inhibitors—selective serotonin reuptake inhibitor (SSRI) antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, fluoroquinolones, antihistamines, omeprazole); or subjects who refuse to avoid consuming fruits (e.g., grapefruit) or related products that affect metabolic enzymes, as well as alcohol, tobacco, caffeinated beverages, and celery-related foods (e.g., Chinese celery, western celery), or refuse to avoid strenuous exercise during the trial period; 17.Subjects with an alcohol breath test result greater than 0 mg/100 ml, or a positive result in the urine multi-drug combination test; 18.(Screening period/admission interview) Female subjects with a positive pregnancy test or who are breastfeeding; female subjects who have had unprotected sexual intercourse within 2 weeks prior to screening; subjects who have used oral contraceptives within 30 days prior to the first administration of the trial drug, or have used long-acting estrogen or progesterone injections or implants within 6 months prior to the first administration of the trial drug; 19.(Screening period/admission interview) Male subjects (or their partners) or female subjects who have plans for pregnancy within 3 months from the time of signing the informed consent form, or who are unable or unwilling to adopt contraceptive measures approved by the researcher during the study period in accordance with the researcher’s guidance; 20.(Screening period interview) Subjects who cannot comply with a unified diet; 21.(Screening period interview) Subjects with swallowing dysfunction; 22.Subjects with poor compliance, or those who cannot abide by the relevant provisions of the study protocol due to personal reasons, and are deemed unsuitable for participation in this clinical study by the researcher.

研究实施时间：

Study execute time：

从 From 2025-10-14 00:00:00至 To 2026-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-12-15 00:00:00 至 To 2026-06-30 00:00:00

干预措施：

Interventions：

组别：	第一部分	样本量：	12
Group：	Part 1	Sample size：	12
干预措施：	采用单中心、随机、开放、三制剂、三周期、交叉设计，受试者根据随机结果三周期分别空腹口服试验药物113口服冻干粉200mg或口服对照药丁苯酞软胶囊0.2g或静脉滴注对照药丁苯酞氯化钠注射液25mg。	干预措施代码：
Intervention：	A single-center, randomized, open-label, three-preparation, three-period, crossover design was adopted. According to the randomization results, subjects received, in three separate periods, an oral dose of 200mg of the test drug 113 oral lyophilized powder, an oral dose of 0.2g of the reference drug butylphthalide soft capsules, or an intravenous infusion of 25mg of the reference drug butylphthalide and sodium chloride injection, all under fasting conditions.	Intervention code：

组别：	第二部分	样本量：	12
Group：	Part 2	Sample size：	12
干预措施：	结合第一部分试验的PK数据，建立PK模型，外推预测获得113口服冻干粉合适的临床给药剂量，计划选择两个给药剂量（T2，T3）进行第二部分研究。采用随机、两周期交叉设计，受试者分别在D1、D8空腹口服试验药物T2（113 口服冻干粉）或试验药物T3（113 口服冻干粉）。	干预措施代码：
Intervention：	Based on the PK data from the first part of the trial, a PK model will be established, and appropriate extrapolation and prediction will be conducted to determine the appropriate clinical doses of 113 oral lyophilized powder. It is planned to select two doses (T2, T3) for the second part of the study, which will adopt a randomized, two-period crossover design. Subjects will receive an oral dose of the test drug T2 (113 oral lyophilized powder) or T3 (113 oral lyophilized powder) under fasting conditions on Day 1 and Day 8, respectively.	Intervention code：

组别：	第三部分	样本量：	24
Group：	Part 3	Sample size：	24
干预措施：	健康受试者多次给药研究拟通过模型推测，选择2个冻干粉给药剂量T4和T5，开展多次给药研究。根据多次给药结果，比较体内蓄积、安全性数据等，再确定113口服冻干粉的临床使用剂量。计划采用单中心、随机、开放试验设计。共分为两个剂量组（剂量组1的给药剂量为T4、剂量组2的给药剂量为T5，根据第一、二部分的试验结果调整），每个剂量组分别入组12例健康受试者，先开展低剂量组。空腹状态下给予113口服冻干粉，每天给药2次（BID），每次给药间隔12h，连续给药6天，其中D6仅早上给药一次。	干预措施代码：
Intervention：	Based on model predictions, two lyophilized powder doses (T4 and T5) will be selected to conduct the multiple-dose study. According to the results of the multiple-dose administration, parameters such as in vivo accumulation and safety data will be compared to further determine the clinical dosage of 113 oral lyophilized powder. A single-center, randomized, open-label trial design is planned. The study will be divided into two dose groups (Dose Group 1 will use dose T4, and Dose Group 2 will use dose T5; both doses will be adjusted based on the trial results of Part 1 and Part 2). Each dose group will enroll 12 healthy subjects, and the low-dose group will be initiated first. The 113 oral lyophilized powder will be administered under fasting conditions, with a frequency of twice daily (BID). The interval between each dose will be 12 hours, and continuous administration will last for 6 days. Notably, only one dose will be given on the morning of Day 6 (D6).	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	湖南	市(区县)：
Country：	China	Province：	Hunan	City：
单位(医院)：	中南大学湘雅三医院	单位级别：	三级甲等
Institution hospital：	The Third Xiangya Hospital of Central South University	Level of the institution：	Grade A of Third-Class Hospitals

测量指标：

Outcomes：

指标中文名：	生命体征	指标类型：	主要指标
Outcome：	Vital Signs	Type：	Primary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

指标中文名：	心电图	指标类型：	主要指标
Outcome：	Electrocardiogram	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	指标类型：	次要指标
Outcome：	Pharmacokinetic Indicators	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	使用后保存	说明
Fate of sample：	Preservation 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	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）：

随机化专员使用SAS软件（9.4或者以上版本）产生随机号表及药物编号表，该随机数据具有重现性，随机数初值种子参数需要保存。

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

The randomization specialist generates the random number table and drug numbering table using SAS software (Version 9.4 or higher). The random data is reproducible, and the initial seed parameter of the random numbers must be saved.

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：

本研究第一、二、三部分均采用随机、开放试验设计，第一、二部分均采用区组随机方法，随机化专员使用 SAS 软件（9.4 或者以上版本）产生随机号表及药物编号表，该随机数据具有重现性，随机数初值种子参数需要保存。第三部分按筛选号从小到大依次分配随机号。为确保在数据统计分析前，生物样本检测分析人员将不获得受试者分组信息及随机给药信息，随机分组表由统计师在试验开始之前直接传递给临床研究中心。

Blinding：

Parts I, II, and III of this study employed a randomised, open-label trial design. Parts I and II utilised block randomisation. The randomisation coordinator generated randomisation and drug numbering tables using SAS software (version 9.4 or higher). This randomisation data is reproducible, and the initial seed parameter for the random number generator must be preserved. For Part III, random numbers were assigned sequentially in ascending order based on the screening number. To ensure that biological sample analysts remained unaware of subject groupings and randomised medication assignments prior to statistical analysis, the randomisation list was delivered directly to the clinical research centre by the statistician before trial commencement.

是否共享原始数据： IPD sharing	否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：	数据采集：由研究者或其授权的 CRC 通过独立的账号进入数据管理系统，进行数据采集。数据管理：数据管理员根据方案设计 eCRF，eCRF 中包含除外部数据外方案中规定的全部数据点。由 EDC 系统直接导出 eCRF（PDF 格式
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Data Collection: The data is collected by the researcher or their authorized CRC through a separate account in the data management system.Data Management: The data manager designs the eCRF according to the protocol. The eCRF contains all the data points specified in the protocol except for external data. The eCRF (in PDF format) is directly exported by the EDC system.
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2025-12-03 15:37:23