ChiCTR2400088023 版本V1.0 版本创建时间2024/08/09 09:58:42 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：

 ChiCTR2400088023 

最近更新日期：

Date of Last Refreshed on：

 2024-08-09 09:58:05 

注册时间：

Date of Registration：

 2024-08-09 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

KEM2104 凝胶贴膏在中国健康受试者中单次/多次给药剂量递增及相对生物利用度研究

Public title：

Study of single/multiple dose escalation and relative bioavailability of KEM2104 gel paste in healthy Chinese subjects

注册题目简写：

English Acronym：

Single multiple dosing and bioavailability study of KEM2104 gel paste

研究课题的正式科学名称：

KEM2104 凝胶贴膏在中国健康受试者中单次/多次给药剂量递增及相对生物利用度研究

Scientific title：

Study of single/multiple dose escalation and relative bioavailability of KEM2104 gel paste in healthy Chinese 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：

黄洁 

研究负责人：

阳国平 

Applicant：

Jie Huang 

Study leader：

Guoping Yang 

申请注册联系人电话：

Applicant telephone：

 +86 18075186566

研究负责人电话：

Study leader's
telephone：

+86 731 88618938

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：

湖南省长沙市河西岳麓区桐梓坡路138号

研究负责人通讯地址：

湖南省长沙市河西岳麓区桐梓坡路138号

Applicant address：

No.138 Tongzipo Road, Yuelu District, Hexi, Changsha City, Hunan Province

Study leader's address：

No. 138, Tongzipo Road, Yuelu District, Hexi, Changsha City, Hunan 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：

中南大学湘雅三医院

Applicant's institution：

Xiangya Third Hospital, Central South University

研究负责人所在单位：

中南大学湘雅三医院

Affiliation of the Leader：

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：

 24092

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：

IRB of the Third Xiangya Hospital of CSU

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-06-20 00:00:00

伦理委员会联系人：

王晓敏

Contact Name of the ethic committee：

Wang XiaoMin

伦理委员会联系地址：

湖南省长沙市河西岳麓区桐梓坡路138号

Contact Address of the ethic committee：

No. 138, Tongzipo Road, Yuelu District, Changsha City, Hunan Province

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 731 88618938

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 xiaominwangcsu@163.com

研究实施负责（组长）单位：

中南大学湘雅三医院

Primary sponsor：

The Third Xiangya Hospital, Central South University

研究实施负责（组长）单位地址：

湖南省长沙市河西岳麓区桐梓坡路138号

Primary sponsor's address：

No. 138, Tongzipo Road, Yuelu District, Changsha City, Hunan 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)：

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：

湖南省长沙市河西岳麓区桐梓坡路138号

Institution
hospital：

The Third Xiangya Hospital, Central South University

Address：

No. 138, Tongzipo Road, Yuelu District, Changsha City, Hunan Province

经费或物资来源：

长沙晶易医药科技股份有限公司

Source(s) of funding：

Changsha Jingyi Pharmaceutical Technology Co., Ltd

研究疾病：

无  

Target disease：

None

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评估KEM2104凝胶贴膏在中国健康受试者中单次/多次给药后的安全性、耐受性及药代动力学特征； ②评估 KEM2104凝胶贴膏与酮咯酸氨丁三醇片的相对生物利用度； ③评估 KEM2104凝胶贴膏的皮肤刺激性及粘附力。  

Objectives of Study：

① To evaluate the safety, tolerability and pharmacokinetic characteristics of KEM2104 gel paste after single/multiple administration in Chinese healthy subjects; ② To evaluate the relative bioavailability of KEM2104 gel paste and ketorolac tropanol tablets; ③ To evaluate the skin irritation and adhesion of KEM2104 gel paste.

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) 试验前充分了解试验目的、性质、试验流程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；
2) 年龄为 18~55 周岁（含临界值）的中国健康男性或女性受试者；
3) 男性及女性体重≥50.0 kg，体重指数（BMI）在 19.0~26.0 kg/m2范围内（包括临界值）；
4) 受试者自筛选访视起至末次给药后 6 个月内无生育计划、无捐精捐卵计划且自愿采取医 学认可的避孕措施，包括并不限于：正确使用男用避孕套、禁欲；或宫内节育器；或任 意一方已行绝育术。

Inclusion criteria

1) Before the test, fully understand the purpose, nature, process and possible adverse reactions of the test, volunteer as a subject, and sign the informed consent;
2) Chinese healthy male or female subjects aged 18-55 years old (including the critical value);
3) Male and female weight ≥50.0 kg, body mass index (BMI) in the range of 19.0~26.0 kg/m2 (including the critical value);
4) The subjects had no fertility plan, no sperm and egg donation plan and voluntarily adopted medically approved contraceptive measures within 6 months from the screening visit to the last dose, including but not limited to: correct use of male condoms, abstinence; Or intrauterine devices; Or either party has been sterilized.

排除标准：

1) 筛选前 3 个月内参加过任何临床试验者；（问诊+联网筛查）；
2) 既往或目前正患有心血管系统、内分泌系统、神经系统（癫痫）、消化系统（消化性溃疡、 胃肠道出血或穿孔）、呼吸系统、泌尿生殖系统、血液系统、免疫系统、精神病学及代谢 异常、传染性疾病等任何临床严重疾病或能干扰试验结果的任何其他疾病，或任何影响试 验过程的其他疾病者；（问诊）；
3) 有特定过敏史（哮喘、荨麻疹、湿疹等）或为过敏体质（如已知对两种或以上物质过敏者）， 或已知对酮咯酸氨丁三醇、阿司匹林和其他非甾体抗炎药过敏者；（问诊）；
4) 患有研究者判断为有临床意义的皮肤疾病（如：湿疹、荨麻疹、特异性皮炎等）者或给药 部位皮肤有胎记、疤痕、纹身，开放性伤口者或毛发旺盛者；（问诊+检查）；
5) 试验前 6 个月内接受过经研究者判断会影响药物吸收、分布、代谢、排泄的手术者；或试 验前 28 天内接受过外科手术，或计划在试验期间进行外科手术者；（问诊）；
6) 试验前 14 天内使用过任何药物或保健品（包括中草药、维生素）者；（问诊）；
7) 试验前 3 个月内献血或大量失血（≥400 mL，女性月经期除外），接受输血或使用血制品 者；（问诊）；
8) 不能忍受静脉穿刺，或静脉采血困难，或有晕针晕血史者；（问诊）；
9) 试验前 1 个月内使用过任何抑制或诱导肝脏对药物代谢的药物或使用过选择性 5-羟色胺 再摄取抑制剂、阿司匹林或其他非甾体抗炎药、丙磺舒、己酮可可碱；（问诊）；
10) 试验前 1 个月内接种过疫苗，或计划在研究期间接种疫苗者；（问诊）；
11) 对饮食有特殊要求，不能遵守统一饮食或吞咽困难者；（问诊）；
12) 试验前 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=250 mL）者 或试验期间不能停止饮用茶、咖啡或含咖啡因的饮料；（问诊）；
13) 嗜烟者或试验前3个月内每日吸烟量多于5支者或试验期间不能停止使用任何烟草类产品 者；（问诊）；
14) 酗酒者或试验前 6 个月内经常饮酒者，即每周饮酒超过 14 单位酒精（1 单位=360 mL 啤 酒或 45 mL 酒精量为 40%的烈酒或 150 mL 葡萄酒）或试验期间不能停止使用任何含酒精 产品者；（问诊）；
15) 药物滥用者或试验前 3 个月使用过软毒品（如：大麻）或试验前 1 年服用硬毒品（如：可 卡因、苯环己哌啶等）；（问诊）；
16) 妊娠期或哺乳期女性，或血妊娠检查异常者；（问诊+检查）；
17) 乙肝表面抗原（HBsAg）、丙型肝炎抗体测定（HCV-AB）、人免疫缺陷病毒抗原抗体初 筛（HIVAg/Ab）、梅毒螺旋体抗体（TP）检查阳性者；
18) 皮肤划痕试验阳性者；
19) 生命体征异常者（收缩压<90 mmHg 或>140 mmHg，舒张压<50 mmHg 或>90 mmHg，脉 搏<50 bpm 或>100 bpm）、或体格检查、心电图、实验室检查（血常规、尿常规、便常规、 血生化、凝血功能检查）经临床医生判定为异常有临床意义者；
20) 受试者可能因为其他原因而不能完成本研究或经研究者判断具有其它不宜参加试验原因 者。
1.每周期入住排除标准1）自上次离院后至入住前有伴随用药、急性疾病且经研究者判断对试验结果有影响者；（问 诊）；
2.每周期入住排除标准2）自上次离院后至入住前服用烟草制品或服用过含有酒精的制品且经研究者判断对试验结果 有影响者；（问诊）；
3.每周期入住排除标准3）自上次离院后至入住前饮用茶、咖啡和/或含咖啡因的饮料且经研究者判断对试验结果有影 响者；（问诊）；
4.每周期入住排除标准4）自上次离院后至入住前发生无保护性性行为者；（问诊）；
5.每周期入住排除标准5）自上次离院后至入住前接种过疫苗或计划在研究期间接种疫苗者；（问诊）；
6.每周期入住排除标准6）入住前 72 h 进食可能影响药物体内代谢的饮食（包括葡萄柚或葡萄柚产品、火龙果、芒果、 甘蓝类蔬菜等）或其他富含黄嘌呤的食物（如凤尾鱼、沙丁鱼、牛肝、牛肾等），或研 究者认为有其他影响药物吸收、分布、代谢、排泄的饮食者或试验期间不能停止进食上 述饮食者；（问诊）；
7.每周期入住排除标准7）生命体征异常有临床意义且研究者认为无法再继续参加试验者；
8.每周期入住排除标准8）药物滥用筛查试验阳性者；
9.每周期入住排除标准9）酒精呼气测试结果＞0.0 mg/100 mL 者；
10.每周期入住排除标准10）女性血妊娠检查异常且有临床意义者；
11.每周期入住排除标准11）给药部位皮肤有异常且研究者判断不适宜继续参加试验者；
12.每周期入住排除标准12）受试者可能因为其他原因而不能完成本研究或经研究者判断具有其它不宜参加试验原因 者。

Exclusion criteria：

1) Participants who have participated in any clinical trial within 3 months before screening; (Consultation + network screening);
2) Have been or are currently suffering from any clinically serious disease of the cardiovascular system, endocrine system, nervous system (epilepsy), digestive system (peptic ulcer, gastrointestinal bleeding or perforation), respiratory system, urogenital system, blood system, immune system, psychiatric and metabolic abnormalities, infectious diseases or any other disease that can interfere with the test results, Or any other disease affecting the testing process; (Consultation);
3) Have a history of specific allergies (asthma, urticaria, eczema, etc.) or are allergic (e.g. are known to be allergic to two or more substances), or are known to be allergic to ketorolac troamine, aspirin and other NSaids; (Consultation);
4) Patients with clinically significant skin diseases (such as eczema, urticaria, specific dermatitis, etc.) or those with birthmarks, scars, tattoos, open wounds, or strong hair on the skin of the drug administration site; (Consultation + examination);
5) Patients who had undergone surgery within 6 months before the trial that the researchers judged would affect drug absorption, distribution, metabolism, and excretion; Had surgery within 28 days prior to the trial, or planned to have surgery during the trial; (Consultation);
6) Used any drugs or health products (including Chinese herbs and vitamins) within 14 days before the test; (Consultation);
7) Those who donated blood or lost a large amount of blood (≥400 mL, excluding female menstrual period) within 3 months before the test, received blood transfusion or used blood products; (Consultation);
8) Can not tolerate venipuncture, or venous blood collection difficulties, or have a history of fainting needle and fainting blood; (Consultation);
9) Use of any drug that inhibits or induces liver metabolism of drugs or selective serotonin reuptake inhibitors, aspirin or other non-steroidal anti-inflammatory drugs, prosulfa, pentoxifylline within 1 month before the test; (Consultation);
10) Those who had been vaccinated within 1 month before the trial or planned to be vaccinated during the study period; (Consultation);
11) People who have special requirements for diet and cannot comply with a unified diet or have difficulty swallowing; (Consultation);
12) Those who consumed excessive amounts of tea, coffee or caffeinated beverages (more than 8 cups, 1 cup =250 mL) per day in the 3 months prior to the trial or did not stop drinking tea, coffee or caffeinated beverages during the trial; (Consultation);
13) Smokers or smokers who smoked more than 5 cigarettes per day in the 3 months before the trial or who could not stop using any tobacco products during the trial; (Consultation);
14) Heavy drinkers or regular drinkers in the six months prior to the trial, i.e. those who drink more than 14 units of alcohol per week (1 unit =360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine) or who cannot stop using any alcoholic products during the trial period; (Consultation);
15) Drug abusers or those who have used soft drugs (e.g., cannabis) in the 3 months prior to the trial or hard drugs (e.g., cocaine, PCP, etc.) in the 1 year prior to the trial; (Consultation);
16) Pregnant or lactating women, or abnormal blood pregnancy tests; (Consultation + examination);
17) Hepatitis B Surface antigen (HBsAg), hepatitis C antibody assay (HCV-AB), human immunodeficiency virus antigen antibody screening (HIVAg/Ab), Treponema pallidum antibody (TP) test positive;
18) Skin scratch test positive;
19) Patients with abnormal vital signs (systolic blood pressure <90 mmHg or >140 mmHg, diastolic blood pressure <50 mmHg or >90 mmHg, Pulse <50 bpm or >100 bpm), or physical examination, electrocardiogram, laboratory examination (blood routine, urine routine, stool routine, blood biochemistry, coagulation function test) determined by the clinician to be abnormal and clinically significant;
20) Subjects may not be able to complete the study for other reasons or have other reasons deemed unsuitable by the investigator.
1.Exclusion criteria for each period of admission 1) Patients with concomitant medication or acute illness from the last discharge to the time before admission and who were judged by the investigator to have an impact on the test results; (Consultation);
2.Exclusion criteria for each period of admission 2) Use of tobacco products or alcohol products from the last discharge to the time before admission, and the investigator determined that the results of the study were affected; (Consultation);
3.Exclusion criteria for each period of admission 3) people who have consumed tea, coffee and/or caffeinated beverages since their last departure from the hospital and before their stay, and who are judged by the investigator to have had an impact on the test results; (Consultation);
4.Exclusion criteria for each period of admission 4) Those who have had unprotected sex from the last time they left the hospital to the time before they checked in; (Consultation);
5.Exclusion criteria for each period of admission 5) Those who have been vaccinated since their last stay and before stay or plan to be vaccinated during the study period; (Consultation);
6.Exclusion criteria for each period of admission 6) Eating a diet (including grapefruit or grapefruit products, dragon fruit, mango, kale vegetables, etc.) or other xanthine-rich foods (such as anchovies, sardines, beef liver, beef kidney, etc.) 72 hours prior to stay that may affect the metabolism of drugs in the body, Or the researcher believes that there are other diet affecting drug absorption, distribution, metabolism, excretion, or can not stop eating the above diet during the study; (Consultation);
7.Exclusion criteria for each period of admission 7) Patients with clinically significant abnormalities in vital signs who are considered by the investigator to be unable to continue participating in the study;
8.Exclusion criteria for each period of admission 8) Drug abuse screening test positive;
9.Exclusion criteria for each period of admission 9) Alcohol breath test results > 0.0 mg/100 mL;
10.Exclusion criteria for each period of admission 10) Abnormal female blood pregnancy test with clinical significance;
11.Exclusion criteria for each period of admission 11) Patients with abnormal skin at the administration site who were judged by the investigator to be unfit to continue participating in the trial;
12.Exclusion criteria for each period of admission 12) Subjects may not be able to complete the study for other reasons or may have other reasons deemed unsuitable by the investigator.

研究实施时间：

Study execute time：

从 From 2024-06-17 00:00:00至 To 2026-06-18 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-08-30 00:00:00 至 To 2025-03-13 00:00:00

干预措施：

Interventions：

组别：

组1

样本量：

 6

Group：

Group 1

Sample size：

干预措施：

酮咯酸氨丁三醇片- KEM2104 凝胶贴膏

干预措施代码：

Intervention：

Ketorolac tropanol tablets- KEM2104 Gel Paste

Intervention code：

组别：

组2

样本量：

 6

Group：

Group 2

Sample size：

干预措施：

KEM2104 凝胶贴膏- 酮咯酸氨丁三醇片

干预措施代码：

Intervention：

KEM2104 Gel Paste- Ketorolac tropanol tablets

Intervention code：

组别：

单次给药组

样本量：

 32

Group：

Single administration group

Sample size：

干预措施：

KEM2104 凝胶贴膏

干预措施代码：

Intervention：

KEM2104 Gel Paste

Intervention code：

组别：

多次给药组

样本量：

 32

Group：

Multiple administration group

Sample size：

干预措施：

KEM2104 凝胶贴膏

干预措施代码：

Intervention：

KEM2104 Gel Paste

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, Central South University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

粘附力数据

指标类型：

次要指标

Outcome：

Adhesion data

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

皮肤刺激性数据

指标类型：

主要指标

Outcome：

Skin irritation data

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性指标

指标类型：

主要指标

Outcome：

Security Indicators

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

指标类型：

主要指标

Outcome：

PK

Type：

Primary indicator

测量时间点：

测量方法：

LC-MS/MS

Measure time point of outcome：

Measure method：

LC-MS/MS

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）：

统计单位利用SAS软件编写随机序列生成随机表

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

The statistical unit utilizes SAS software to write random sequences to generate random tables

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：

开放标签

Blinding：

Open-label

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）：

https://edc.clinflash.com

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

https://edc.clinflash.com

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： 北京中兴正远科技有限公司，I期/BE临床试验全过程数据采集管理系统，网址：http://183.169.36.207/Login?ReturnUrl=%2f（内网系统） EDC：嘉兴易迪希计算机技术有限公司，网址为https://edc.clinflash.com

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

CRF: Beijing Zhongxing Zhengyuan Technology Co., LTD，Phase I/BE clinical trial whole process data collection management system at http://183.169.36.207/Login?ReturnUrl=%2f (this system is an intranet system) Data Management: Jiaxing Edixi Computer Technology Co.，The web address is https://edc.clinflash.com

数据与安全监察委员会：

Data and Safety Monitoring Committee：

无/No

注册人：

Name of Registration：

  2024-08-09 09:58:05