ChiCTR2300070056 版本V1.5 版本创建时间2023/07/09 22:07:09 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：

 ChiCTR2300070056 

最近更新日期：

Date of Last Refreshed on：

 2023-07-09 22:02:26 

注册时间：

Date of Registration：

 2023-03-31 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

TUL01101软膏在健康成人受试者中单次/多次给药的安全性、耐受性、药代动力学特征

Public title：

Safety, tolerability, and pharmacokinetic profile of TUL01101 ointment in single/multiple doses in healthy adult subjects

注册题目简写：

English Acronym：

研究课题的正式科学名称：

TUL01101软膏在健康成人受试者中单次/多次给药的安全性、耐受性、药代动力学特征

Scientific title：

Safety, tolerability, and pharmacokinetic profile of TUL01101 ointment in single/multiple doses in healthy adult 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：

张美琳 

研究负责人：

阳国平 

Applicant：

Meilin Zhang 

Study leader：

Guoping Yang 

申请注册联系人电话：

Applicant telephone：

 +86 18723596158

研究负责人电话：

Study leader's
telephone：

+86 731 89918665

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：

 zhangmeilin69@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：

湖南省长沙市岳麓区桐梓坡路172号

研究负责人通讯地址：

湖南省长沙市岳麓区桐梓坡路138号

Applicant address：

No. 172, Tongzipo Road, Yuelu District, Changsha City, Hunan Province

Study leader's address：

No. 138, Tongzipo Road, Yuelu District, 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临床试验中心

Applicant's institution：

Clinical Trial Center of the Third Xiangya Hospital of 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中心

Affiliation of the Leader：

Clinical Trial Center of the Third Xiangya Hospital of 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：

 22164

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，theThird Xiangya Hospital of Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

 2022-12-21 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：

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：

IRB，theThird Xiangya Hospital of Central South University，138Tongzipo Road，Yuelu District，Changsha，Hunan，China

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：

研究实施负责（组长）单位：

中南大学湘雅三医院临床试验中心

Primary sponsor：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

研究实施负责（组长）单位地址：

湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

138Tongzipo Road，Yuelu District，Changsha，Hunan，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)：

长沙

Country：

China

Province：

Hunan

City：

Changsha

单位(医院)：

中南大学湘雅三医院

具体地址：

湖南省长沙市岳麓区桐梓坡路138号

Institution
hospital：

Third Xiangya Hospital, Central South University

Address：

138Tongzipo Road，Yuelu District，Changsha，Hunan，China

经费或物资来源：

珠海联邦制药股份有限公司

Source(s) of funding：

Zhuhai Federal Pharmaceutical Co.

研究疾病：

特应性皮炎  

Target disease：

Atopic dermatitis，AD

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：评估TULO1101软膏在健康成人受试者中单次和多次局部皮肤给药的安全性和耐受性 次要目的：评估TULO1101软膏在健康成人受试者中单次和多次局部皮肤给药的药代动力学（PK）特征  

Objectives of Study：

Primary objective: To evaluate the safety and tolerability of TULO1101 Ointment in healthy adult subjects with single and multiple topical dermal administrations Secondary objective: To evaluate the pharmacokinetic (PK) profile of TULO1101 Ointment in healthy adult subjects for single and multiple topical dermal administrations

药物成份或治疗方案详述：

TUL01101软膏为一种JAK激酶抑制剂，活性药物分子式是C22H25F2N5O2辅料有白凡士林、白蜂蜡、液状石蜡。 采用随机、双盲、安慰剂对照、单次/多次给药剂量递增的临床试验设计，选择健康成人受试者单次涂抹TULO1101软膏，观察3天，研究者评估受试者耐受且无重大安全性风险后，则于D4开始进行每天两次，持续7天的多次给药研究，以评估TULO1101软膏的安全性、耐受性和PK特征。 将根据Cohort1单次和多次给药的安全性、耐受性等结果，经研究者综合评估确认安全后，再按每队列的剂量逐组进行Cohort2-Cohort4的单次和多次给药（浓度2%）研究。每次只开展一个队列组的研究，每个队列组均入组10例受试者（每组按4：1比例随机入组TULO1101软膏8例，安慰剂2例），总计入组40例受试者。 

Description for medicine or protocol of treatment in detail：

TUL01101 ointment is a JAK kinase inhibitor, the active drug molecular formula is C22H25F2N5O2 excipients are white petroleum jelly, white beeswax, liquid paraffin Using a randomized, double-blind, placebo-controlled, single/multiple dose escalation clinical trial design, healthy adult subjects were selected for a single application of TULO1101 ointment for 3 days of observation, and after the investigator assessed that the subjects tolerated it without significant safety risk, then a multiple dosing study was conducted twice daily for 7 days starting at D4 to evaluate the safety, tolerability and PK characteristics. After the safety and tolerability results of single and multiple doses of Cohort1 are confirmed by the investigator's comprehensive assessment, single and multiple dose (2% concentration) studies of Cohort2-Cohort4 will be conducted on a group-by-group basis at each cohort's dose. Only one cohort group was studied at a time, with 10 subjects enrolled in each cohort group (8 in each group randomized 4:1 to TULO1101 ointment and 2 to placebo), for a total of 40 subjects. 

纳入标准：

1）性别：男性或女性
2）年龄：年龄为18-55岁（含临界值）
3)筛选时男性体重≥50kg，女性体重≥45kg，体重指数（BMI)在19-26kg/m2之间（BMl=体重（kg）/身高2（m2）），包括临界值：
4）筛选时及给药前目标涂药区皮肤无破溃、损伤、晒伤、红肿、皮疹、或异常发热及纹身、胎记、皮肤瘢痕、皮肤穿孔等情况，且同意剃除该部位皮肤的毛发（如有）；
5）受试者（包括其伴侣）在给药前2周至研究结束后3个月内自愿采取适当的避孕措施（具体避孕措施见附录1），且研究结束后3个月内无捐麟精子或卵子计划：
6）受试者能够和研究者进行良好的沟通，并且理解和遵守本试验的各项要求：
7）受试者自愿参加研究，并签署书面的知情同意书。

Inclusion criteria

1) Gender: male or female
2) Age: age 18-55 years (including the threshold)
3) Weight ≥ 50kg for men and ≥ 45kg for women at the time of screening, with a body mass index (BMI) between 19-26kg/m2 (BMl = weight (kg)/height 2 (m2)), including the critical value of
4) No breakage, injury, sunburn, redness, rash, or abnormal fever and tattoo, birthmark, skin scar, skin perforation, etc., on the skin of the target application area at the time of screening and prior to administration, and consent to shave the skin of the area (if any);
5) Subjects (including their partners) voluntarily use appropriate contraception (see Appendix 1 for specific contraceptive measures) from 2 weeks prior to dosing to 3 months after the end of the study, and have no plans to donate sperm or eggs within 3 months of the end of the study:
6) The subject is able to communicate well with the investigator and understands and complies with the requirements of this trial:
7) Subjects voluntarily participate in the study and sign a written informed consent form.

排除标准：

符合一条或多条下列标准的受试者将被排除：
1)对本研究药物或其制剂成分过敏者,或既往有过敏性疾病(如过敏性鼻炎、过敏性哮喘)、药物过敏史、皮肤过敏史(包括但不限于对贴膏过敏，对金属、化妆品或家居用品有接触性皮炎)者，或已知为高敏体质者，
2)既往有严重的或筛选时有临床意义的疾病或异常情况，包括但不限于心血管系统、神经系统、呼吸系统、血液和淋巴系统、消化系统、免疫系统、肝脏、肾脏、代谢及骨骼等系统疾病或精神病学疾病
3)筛选前 5 年内患有癌症(除了仅通过低温冷冻手术或手术切除治愈的鳞状细胞癌、基底细胞癌或原位皮肤癌)者;
4)筛选时患皮肤疾病，包括银屑病、湿疹、瘤疮、特应性皮炎、发育不良痣、或其他皮肤病变等，或可能影响试验药物的给药和观察者;
5)筛选前一年内有频繁的感染病史(发作次数3 次)，或给药前3个月内有复发性口腔疯疹、生殖器痕疹、带状疯疹等复发性病毒感染史者，或筛选前1个月内发生过经研究者判定有临床意义的感染者，包括急慢性感染如脓肿、疗、痈等局部感染、呼吸道感染泌尿生殖道感染、全身感染等;
6)筛选时临床症状、体征、实验室检查或X线胸片检测提示有活动性结核者7)筛选前1个月内接受过对试验评价有影响的手术，或自研究开始至结束后1个月内计划手术者;
8)筛选时生命体征异常者(收缩压90 mmHg 或>140mmHg，舒张压<50mmHg 或>90mmHg:心率<50bpm或>100bpm)或心电图检查异常者 (男性OTc间期>450ms，女性OTc 间期>470ms)或体格检查、胸片、B 超、实验室检查异常有临床意义 (以临床研究医生判断为准)者:
9)筛选时乙型肝炎表面抗原、丙型肝炎抗体、梅毒抗体或 HIV 抗体检查阳性者;
10)在给药前2周内因任何原因有用药史(包括局部用药、保健品、中草药)，或研究者确定所用药物距离本试验开始给药的时间间隔<5 个半衰期者;
11)筛选前 30 天内使用过任何抑制或诱导肝脏对药物代谢的药物(如:诱导剂一巴比妥类卡马西平、苯妥英、糖皮质激素、奥美拉哗:抑制剂一SSRI类抗抑郁药、西咪替丁、地尔硫卓、大环内酷类、硝基咪哗类、镇静催眠药、维拉帕米、氟峰诺酮类、抗组胺类)者;
12)筛选前1个月内接种过任何活疫苗或需要在研究期间(包括研究药物末次给药后30天内) 接种活疫苗;
13)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、苯环已派呢等) 或尿液毒品检测阳性者;
14)筛选前 3 个月内失血或献血超过 200 mL，或接受过血液或血液成份输注者;
15)筛选前 3 个月内参加过任何药物或医疗器械的临床试验且给药者 (含安慰剂组)，以未次服药时间计算;
16)筛选前3 个月内每日吸烟超过5 支香烟或等量烟草的或者试验期间不能戒烟者
17)筛选前28天内女性每周饮酒超过7杯或男性每周饮酒超过14杯1杯=5司(150mL)葡萄酒=12盎司(360mL)啤酒=1.5司(45mL)烈酒)，或首次给药前48 小时内服用过任何含酒精的制品，或在基线访视时酒精呼气试验为阳性者;
18)筛选前 14 天内饮用过量 (一天8 杯以上，1杯=200mL) 茶、咖啡或含咖啡因的饮料或食用葡萄柚(西柚)、或富含黄嫖吟的食物或饮料者，或给药前 48 小时内及试验期间不能停止食用富含黄噪吟成分的食物或饮料(如巧克力、茶、咖啡及可乐等)、或葡萄柚(西柚)或柚子以及含葡萄柚或柚子成分的产品(西柚汁、柚子汁等)者;
19)妊娠期或哺乳期女性!
20)采血困难或不能耐受静脉穿刺者，有量针量血史者:
21)对饮食有特殊要求，不能遵守统一饮食者;
22)研究者认为不适合参加临床试验的其他情况。

Exclusion criteria：

Subjects who meet one or more of the following criteria will be excluded!
1) Persons who are allergic to this study drug or its formulation components, or who have previous allergic disease (e.g., allergic rhinitis, allergic asthma), history of drug allergy, history of skin allergy (including but not limited to allergy to creams, contact dermatitis to metals, cosmetics or household products), or known hypersensitivity.
2) previous serious or clinically significant disease or abnormality at screening, including but not limited to cardiovascular, neurological, respiratory, hematologic and lymphatic, digestive, immune, hepatic, renal, metabolic and skeletal system diseases or psychiatric disorders
3) Cancer (other than squamous cell carcinoma, basal cell carcinoma or skin cancer in situ cured by cryosurgery or surgical excision only) within 5 years prior to screening.
4) Skin disease at the time of screening, including psoriasis, eczema, tuberculosis, atopic dermatitis, dysplastic nevus, or other skin lesions, or that may interfere with the administration and observation of the test drug.
5) A history of frequent infections (3 episodes) within one year prior to screening, or a history of recurrent viral infections such as recurrent oral rash, genital rash, or zoster within 3 months prior to drug administration, or an infection that has been judged by the investigator to be clinically significant within 1 month prior to screening, including acute and chronic infections such as abscess, treatment, carbuncle, and other local infections, respiratory tract infections genitourinary tract infections, and systemic infections.
6) Clinical symptoms, signs, laboratory tests or X-ray chest tests suggestive of active tuberculosis at the time of screening 7) Surgery within 1 month prior to screening that had an impact on the evaluation of the trial, or surgery planned within 1 month from the start to the end of the study.
8) Abnormal vital signs at screening (systolic blood pressure 90 mmHg or >140 mmHg, diastolic blood pressure <50 mmHg or >90 mmHg: heart rate <50 bpm or >100 bpm) or abnormal electrocardiogram (OTc interval >450 ms for men, OTc interval >470 ms for women) or abnormal physical examination, chest X-ray, B-ultrasound, laboratory tests with clinical significance (as determined by the clinician).
9) Positive hepatitis B surface antigen, hepatitis C antibody, syphilis antibody or HIV antibody test at screening
10) History of drug use for any reason (including topical, nutraceutical, herbal) within 2 weeks prior to dosing, or if the investigator determines that the drug used is <5 half-lives from the start of dosing in this trial;
11) Use of any drug that inhibits or induces hepatic metabolism of the drug within 30 days prior to screening (e.g., inducers a barbiturate carbamazepine, phenytoin, glucocorticoids, omeprazole. Inhibitors I SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil, flufenoxolone, antihistamines).
12) Have received any live vaccine within 1 month prior to screening or require live vaccination during the study period (including within 30 days of the last dose of study drug).
13) Drug abusers or those who have used soft drugs (e.g., marijuana) in the 3 months prior to the test or hard drugs (e.g., cocaine, phencyclidine, etc.) in the 1 year prior to the test or who have tested positive for urine drugs.
14) Blood loss or donation of more than 200 mL in the 3 months prior to screening, or who have received a blood or blood component transfusion.
15) Participated in a clinical trial of any drug or medical device within 3 months prior to screening and administered medication (including placebo group), based on the time of the last dose.
16) smokers who smoked more than 5 cigarettes or equivalent per day within 3 months prior to screening or who were unable to quit smoking during the trial
17) Drinking more than 7 drinks per week for women or 14 drinks per week for men within 28 days prior to screening (1 drink = 5 glasses (150 mL) of wine = 12 ounces (360 mL) of beer = 1.5 ounces (45 mL) of spirits), or having taken any alcoholic product within 48 hours prior to the first dose, or having a positive breath test for alcohol at the baseline visit.
18) Excessive consumption (more than 8 cups a day, 1 cup = 200mL) of tea, coffee or caffeinated beverages or grapefruit (grapefruit), or food or beverages rich in yellow jelly within 14 days prior to screening, or inability to stop consuming food or beverages rich in yellow jelly (e.g. chocolate, tea, coffee and cola), or grapefruit (grapefruit) or pomelo and products containing grapefruit or pomelo (grapefruit juice, pomelo juice, etc.).
19) Pregnant or lactating women!
20)Those who have difficulty in blood collection or cannot tolerate venipuncture, those who have a history of measuring blood with a needle:
21)Those who have special dietary requirements and cannot comply with a uniform diet;
22)Other conditions that the investigator considers unsuitable for participation in clinical trials.

研究实施时间：

Study execute time：

从 From 2023-03-31 00:00:00至 To 2026-03-30 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2023-04-01 00:00:00 至 To 2024-03-28 00:00:00

干预措施：

Interventions：

组别：

Cohort1

样本量：

 10

Group：

Cohort1

Sample size：

干预措施：

单次涂抹5g1% TUL01101软膏，给药面积10%BSA, 观察3 天，研究者评估受试者耐受且无重大安全性风险后，则于D4 开始进行每天两次，持续 7天的多次给药研究，以评估 TUL01101 软膏的安全性、耐受性和 PK 特征。每个队列组均入组 10 例受试者(每组按 4:1 比例随机入组TUL01101 软膏8例，安慰剂2例)

干预措施代码：

Intervention：

After a single application of 5 g of 1% TUL01101 ointment, administered over an area of 10% BSA, for 3 days, and after the investigator has assessed that the subject is tolerant and there are no significant safety risks, a multiple dosing study is conducted twice daily for 7 days starting at D4 to evaluate the safety, tolerability, and PK characteristics of TUL01101 ointment. 10 subjects were enrolled in each cohort group (8 cases of TUL01101 ointment and 2 cases of placebo were randomly assigned to each group in a 4:1 ratio)

Intervention code：

组别：

Cohort2

样本量：

 10

Group：

Cohort2

Sample size：

干预措施：

将根据 Cohort1 单次和多次给药的安全性、耐受性等结果，经研究者综合评估确认安全后，再按每队列的剂量逐组进行 Cohort2~Cohort4 的单次和多次给药(浓度 2%)研究。Day1至Day3Cohort2在给药区域涂抹5gD4-D9连续每天给药两次，给药面积10%BSA队列组入组 10 例受试者(每组按 4:1 比例随机入组TUL01101 软膏8例，安慰剂2例)

干预措施代码：

Intervention：

Single and multiple dosing (2% concentration) studies of Cohort2 to Cohort4 will be conducted group by group at doses per cohort based on the results of safety and tolerability of single and multiple dosing of Cohort1, and after safety is confirmed by comprehensive assessment by the investigator. From Day1 to Day3Cohort2, 5gD4-D9 was applied twice a day to the administration area, with a 10% administration area. 10 subjects were randomly assigned to the BSA cohort group (8 cases of TUL01101 ointment and 2 cases of placebo were randomly assigned to each group in a 4:1 ratio)

Intervention code：

组别：

Cohort3

样本量：

 10

Group：

Cohort3

Sample size：

干预措施：

Day1至Day3Cohort3在给药区域涂抹10g浓度2%D4-D9连续每天给药两次连续给药7日，给药面积20%BSA队列组入组 10 例受试者(每组按 4:1 比例随机入组TUL01101 软膏8例，安慰剂2例)

干预措施代码：

Intervention：

Day1 to Day3Cohort3Apply 10g of concentration 2% D4-D9 to the dosing area twice daily for 7 consecutive days, dosing area 20% BSA10 subjects were enrolled in the cohort group (8 subjects were randomized to TUL01101 ointment and 2 subjects to placebo in a 4:1 ratio in each group)

Intervention code：

组别：

Cohort4

样本量：

 10

Group：

Cohort4

Sample size：

干预措施：

Day1至Day3Cohort4在给药区域涂抹15g浓度2%D4-D9连续每天给药两次连续给药7日，给药面积30%BSA队列组入组 10 例受试者(每组按 4:1 比例随机入组TUL01101 软膏8例，安慰剂2例)

干预措施代码：

Intervention：

Day1 to Day3Cohort4Apply10 subjects were enrolled in the cohort group (8 subjects were randomized to TUL01101 ointment and 2 subjects to placebo in a 4:1 ratio in each group) 15g concentration of 2% D4-D9 to the dosing area twice daily for 7 consecutive days, 30% BSA on the dosing area

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)：

 Changsha 

Country：

China

Province：

Hunan

City：

长沙

单位(医院)：

 中南大学湘雅三医院 

单位级别：

 三甲 

Institution
hospital：

Third Xiangya Hospital, Central South University

Level of the institution：

Triple A

测量指标：

Outcomes：

指标中文名：

不良反应

指标类型：

主要指标

Outcome：

Adverse reactions

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件

指标类型：

主要指标

Outcome：

Adverse Events

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

TUL01101药代动力学

指标类型：

次要指标

Outcome：

TUL01101 Pharmacokinetics

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

主要代谢产物M3药代动力学

指标类型：

次要指标

Outcome：

Major metabolites M3 pharmacokinetics

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

稳态PK参数

指标类型：

次要指标

Outcome：

Steady-state PK parameters

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：

标本中文名：

粪便

组织：

Sample Name：

Feces

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 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）：

本试验每队列组分别随机，采用区组随机化方法。由统计单位随机人员以 SAS 软件(9.4 或以上版本)产生随机号以及随机号所对应治疗组别。每个队列组生成一个随机表(盲底)密封，一式三份，密封后分别保存在临床单位、申办单位和生物检测单位(PK)。受试者按照签署知情同意书的顺序获取筛选号。筛选号命名规则为 S+TUL+四位数字，如 S-TUL-1001，以此类推。其中四位数中第1 个数字代表队列组，后3 位数代表顺序号。入组成功的受试者获得随机号。随机号命名方式如下，TUL4四位数字，其中四位数中第1个数字代表队列组,后3位数代表顺序号，第一个队列组TUL-1001~TUL-1010第二个队列组 TUL-2001~TUL-2010。以此类推。

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

Each cohort group in this trial was randomized separately, using a zone group randomization method. The randomization number and the treatment group corresponding to the randomization number were generated by the statistical unit randomizer using SAS software (version 9.4 or above). A randomization form (blinded bottom

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：

本研究的所有队列组采用双盲的设计：试验药和安慰剂外观，大小、气味等一致，每个队列组试验用药品均使用相同的外包装盒，每名受试者使用相同编号的试验用药品。药物现场编盲由统计单位人员和申办者与本试验无关人员参加,随机号即作为药物盲法实施的药物号,将已形成的随机号(药物号)填写(或粘贴) 在标签上。编盲过程形成编盲记录保存。

Blinding：

A double-blind design was used for all cohort groups of this study: the test drug and placebo were identical in appearance, size, and odor, and the same outer box was used for the test drug in each cohort group, with the same numbered test drug used for each subject. The randomization number was used as the drug number for the implementation of drug blinding, and the randomization number (drug number) was filled in (or pasted) on the label. The blinding process will be recorded and kept as a blinding record.

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

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）：

NA

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

NA

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：

本次试验采用电子化数据管理，使用电子数据采集系统(DAS forEDC6.0或以上版本)，数据管理流程详见数据管理计划(DMP)。 DMP作为数据管理的指导性文件，由数据管理员(DM)撰写，申办方批准，数据管理工作将根据DMP定义的时间、内容及方法进行。

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

This trial adopts electronic data management, using an electronic data acquisition system (DAS forEDC version 6.0 or above), and the data management process is detailed in the Data Management Plan (DMP). As a guiding document for data management, the DMP is written by the data administrator (DM) and approved by the sponsor, and the data management work will be carried out according to the time, content and method defined by the DMP.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2023-03-31 16:22:42