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：	ChiCTR1800017253
最近更新日期： Date of Last Refreshed on：	2018-07-19 12:01:04
注册时间： Date of Registration：	2018-07-19 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	中国慢性疼痛受试者空腹状态下比较OTR(防篡改盐酸羟考酮缓释片)40 mg和奥施康定40 mg羟考酮药代动力学的开放、单剂、随机、交叉对照研究
Public title：	An Open-label, Single Dose, Randomised, Cross-over Study to Determine the Fasted State pharmacokinetics of Oxycodone from Oxycodone Tamper Resistant (OTR) Tablet 40 mg and OXYCONTIN Tablet 40 mg in Chinese Subjects with Chronic Pain
注册题目简写：
English Acronym：
研究课题的正式科学名称：	中国慢性疼痛受试者空腹状态下比较OTR(防篡改盐酸羟考酮缓释片)40 mg和奥施康定40 mg羟考酮药代动力学的开放、单剂、随机、交叉对照研究
Scientific title：	An Open-label, Single Dose, Randomised, Cross-over Study to Determine the Fasted State pharmacokinetics of Oxycodone from Oxycodone Tamper Resistant (OTR) Tablet 40 mg and OXYCONTIN Tablet 40 mg in Chinese Subjects with Chronic Pain
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：	罗柱	研究负责人：	罗柱
Applicant：	LUO ZHU	Study leader：	LUO ZHU
申请注册联系人电话： Applicant telephone：	+86 13608096720	研究负责人电话： Study leader's telephone：	+86 13608096720
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：	luozhu720@163.com	研究负责人电子邮件： Study leader's E-mail：	luozhu720@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：	中国四川成都国学巷37号四川大学华西医院国家药物临床试验机构/GCP中心	研究负责人通讯地址：	中国四川成都国学巷37号四川大学华西医院国家药物临床试验机构/GCP中心
Applicant address：	37 Guoxuexiang, Wuhou District, Chengdu, Sichuan, China	Study leader's address：	37 Guoxuexiang, Wuhou District, Chengdu, Sichuan, 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：	四川大学华西医院
Applicant's institution：	West China Hospital, Sichuan University
研究负责人所在单位：	四川大学华西医院
Affiliation of the Leader：	West China Hospital, Sichuan 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：	2016年临床试验西药审119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：	四川大学华西医院伦理委员会
Name of the ethic committee：	Ethics Committee of West China Hospital, Sichuan University
伦理委员会批准日期： Date of approved by ethic committee：	2016-04-21 00:00:00
伦理委员会联系人：	李娜
Contact Name of the ethic committee：	Ethics Committee of West China Hospital, Sichuan University
伦理委员会联系地址：	中国四川成都国学巷37号四川大学华西医院第八教学楼4楼
Contact Address of the ethic committee：	4th floor, 8th Teaching Building, West China Hospital, Sichuan University, 37 Guoxuexiang, Wuhou District, Chengdu, Sichuan, China
伦理委员会联系人电话： Contact phone of the ethic committee：		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：

四川大学华西医院

Primary sponsor：

West China Hospital, Sichuan University

研究实施负责（组长）单位地址：

国四川成都国学巷37号四川大学华西医院国家药物临床试验机构/GCP中心

Primary sponsor's address：

37 Guoxuexiang, Chengdu, 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)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	萌蒂（中国）制药有限公司	具体地址：	北京市朝阳区建国门外大街甲6号中环世贸中心D座18层 100022
Institution hospital：	Mundipharma (China) Pharmaceutical Co. Ltd	Address：	18F, Tower D, Central International Trade Center 6A Jianguomenwai Avenue Chaoyang District Beijing, China 100022

国家：	中国	省(直辖市)：	北京	市(区县)：
Country：	China	Province：	Beijing	City：
单位(医院)：	萌蒂（中国）制药有限公司	具体地址：	北京市朝阳区建国门外大街甲6号中环世贸中心D座18层 100022
Institution hospital：	Mundipharma (China) Pharmaceutical Co. Ltd	Address：	18F, Tower D, Central International Trade Center 6A Jianguomenwai Avenue Chaoyang District Beijing, China 100022

经费或物资来源：

萌蒂（中国）制药有限公司

Source(s) of funding：

Mundipharma (China) Pharmaceutical Co. Ltd

研究疾病：

慢性疼痛

Target disease：

Chronic pain

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：

确定OTR 40 mg（片剂）与奥施康定 40 mg（片剂）在空腹状态下具有生物等效性（BE）; 评估中国慢性疼痛受试者空腹状态下服用OTR 40 mg（片剂）和奥施康定片40 mg（片剂）的安全性。

Objectives of Study：

To confirm the bioequivalence (BE) of OTR? tablet 40 mg and OXYCONTIN? tablet 40 mg in a fasted state. To assess the safety of OTR? tablet 40 mg and OXYCONTIN? tablet 40 mg, when given to Chinese subjects with chronic pain in a fasted state.

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. Chinese male or female subjects with histories of chronic pain regardless of the aetiology, aged 18-55 years both inclusive;
2. The average pain over the last 24 hours should be scored < 4 assessed with Numeric Rating Scales (NRS), when not receiving analgesics. The pain condition had been kept stable at least in the past 7 days prior to entering into the screening and was expected to be stable during the study duration;
3. Body weight ≥ 45 kg and a body mass index (BMI) ≥ 18 and ≤ 28 kg/m2;
4. Karnofsky score of Performance Status ≥ 70;
5. Willing to take all the food supplied while the subject was in the Study Center;
6. Be able to read, understand, and sign written Informed Consent Form (ICF) prior to study participation and be willing to follow the protocol requirements;
7. Willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control was defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, some Intrauterine Device (IUD), sexual abstinence, or vasectomised partner;
8. Female subjects, including those up to less than one year post-menopausal, must have a negative serum pregnancy test and be non-lactating.

排除标准：

1. 正在服用或在接受研究药物治疗前的过去14天内服用过阿片类药物；
2. 有任何阿片类、纳曲酮、纳洛酮或相关化合物过敏史，或有OTR片和奥施康定?产品性能概要中详述的任何禁忌症；
3. 既往或目前的任何可干扰药物吸收、分布、代谢或排泄的疾病；
4. 可能患有麻痹性肠梗阻、急腹症、或需进行腹部手术；
5. 患有胆道疾病、胰腺炎、前列腺肥大、或肾上腺皮质功能不全；
6. 患有呼吸抑制、肺源性心脏病或慢性支气管哮喘；
7. 有癫痫发作或有症状的头部外伤病史；
8. 肝功能异常（筛选期丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）或总胆红素值超过正常值上限（ULN））或肾功能异常（筛选期血清肌酐值超过ULN）注：如果ALT、AST、或总胆红素在ULN的1～1.2倍之间并且研究者证实无临床意义，经申办方批准后可能招募该受试者；
9. 过去4周内除慢性疼痛原发病外患有其他严重疾病；
10. 在试验期间不能停用单胺氧化酶抑制剂，或服用研究药物前停用单胺氧化酶抑制剂不到2周；
11. 目前或服用研究药物前4周内使用三环抗抑郁剂；
12. 服用研究药物前4周内使用过任何抑制细胞色素P450 3A4（CYP3A4）类药物（如醋竹桃霉素、酮康唑、孕二烯炔酮等）或诱导CYP3A4类药物（如糖皮质激素、巴比妥类、利福平等）；
13. 服用研究药物前4周内使用过任何抑制细胞色素P450 2D6（CYP2D6）类药物（如氟西汀、奎尼丁、利托那韦等）或诱导CYP2D6类药物（如地塞米松、利福平、格鲁米特等）；
14. 服用研究药物前45天内有吸烟史（吸烟者或偶尔吸烟者），且拒绝在研究期间戒烟。按照世界卫生组织（WHO）规定，吸烟者的定义为每天至少吸1支烟且连续吸烟达6个月以上；偶尔吸烟者的定义为每周吸烟超过4次，每天吸烟少于1支且连续吸烟6个月以上；
15. 有酗酒或药物滥用史。酗酒定义为定期饮酒超过14次/周（1次 = 150 mL葡萄酒或360 mL啤酒或45 mL烈酒）；
16. 给予研究药物前48小时内饮用酒精性饮料，给予研究药物后至少48小时拒绝戒除饮酒；
17. 拒绝在服用研究药物前10小时至服用后4小时内禁食，拒绝在试验过程中禁用含咖啡类或嘌呤类饮食；
18. HBsAg、HCV抗体、HIV抗体或梅毒抗体结果阳性；
19. 研究前尿检阿片类、巴比妥类、安菲他明、可卡因代谢产物、美沙酮、苯二氮卓类、苯环利定、甲基苯丙胺或大麻酚类阳性，或酒精呼气测试阳性；
20. 任何病因引起的频发恶心或呕吐史；
21. 服用研究药物前30天内或研究期间捐献血液或血液制品，本方案中要求的除外；
22. 在进入本试验前30天内参与其他临床研究；

Exclusion criteria：

1. Subjects who were currently taking opioids or have used opioids in the past 14 days prior to receiving the IMP;
2. Had hypersensitivity history to any opioids, naltrexone, naloxone, or related compounds or any contraindications as detailed in the OTR? and OXYCONTIN? tablet Summary of Product Characteristics;
3. Histories of or any current conditions that might interfere with drug absorption, distribution, metabolism, or excretion;
4. Subjects who were likely to have paralytic ileus or acute abdomen or to require an operation on abdominal region;
5. Subjects with biliary tract diseases, pancreatitis, prostatic hypertrophy, or corticoadrenal insufficiency;
6. Subjects with respiratory depression, corpulmonale, or chronic bronchial asthma;
7. Any history of seizures or symptomatic head trauma;
8. Subjects with abnormal liver function (values exceeding the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin during the Screening Phase) or abnormal renal function (values exceeding the ULN for serum creatinine during the Screening Phase). Note: if the values of ALT, AST or total bilirubin were between 1 to 1.2 times of ULN and confirmed not clinically significant by the Investigators, the subject may be recruited after getting the approval from Sponsor;
9. Any other significant illness other than the primary disease of chronic pain during the 4 weeks preceding the entry into this study;
10. Subjects who were unable to stop taking monoamine oxidase inhibitors during this trial period or time lapses less than 2 weeks since drug withdrawal prior to the IMP administration;
11. Subjects who were currently taking tricyclic antidepressants or had used tricyclic antidepressants within 4 weeks prior to the IMP administration;
12. Subjects who had used any medicinal product which inhibits CYP3A4 (e.g. troleandomycin, ketoconazole, gestodene, etc.) or induces CYP3A4 (e.g. glucocorticoids, barbiturates, rifampicin, etc.) within 4 weeks prior to the IMP administration;
13. Subjects who had used any medicinal product which inhibits CYP2D6 (e.g. fluoxetine, quinidine, ritonavir, etc.) or induces CYP2D6 (e.g. dexamethasone, rifampicin, glutethimide, etc.) within 4 weeks prior to the IMP administration.
14. Histories of smoking (being a smoker or an occasional smoker) within 45 days prior to the IMP administration and refusal to abstain from smoking during the study. According to World Health Organization (WHO), a smoker is defined as having smoked at least 1 cigarette per day continuously for more than 6 months and an occasional smoker is defined as having smoked for more than 4 times per week and less than 1 cigarette per day continuously for more than 6 months;
15. Subjects with histories of alcoholism or drug abuse. Alcoholism is defined as regular alcohol consumption exceeding 14 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor).
16. Consumption of alcoholic beverages within 48 hours before IMPadministration, and refusal to abstain from alcohol for at least 48 hours after IMP administration;
17. Refusal to abstain from food for 10 hours preceding and 4 hours following administration of the IMP and to abstain from caffeine or xanthine entirely during each confinement;
18. Positive Hepatitis B Surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV), anti-Human Immunodeficiency Virus (HIV), or syphilis antibody test result;
19. Urine screening before study was positive for opioids, barbiturates, amphetamines, cocaine metabolites, methadone, benzodiazepines, phencyclidine, methamphetamine, or cannabinoids. Or alcohol breath test was positive
20. Any history of frequent nausea or emesis regardless of aetiology;
21. Blood or blood products donated within 30 days prior to administration of the IMPs or anytime during the study, except as required by this protocol;
22. Subjects who participated in a clinical research study within 30 days of study entry.

研究实施时间：

Study execute time：

从 From 2018-07-20 00:00:00至 To 2018-09-30 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2018-07-20 00:00:00 至 To 2018-08-30 00:00:00

干预措施：

Interventions：

组别：	试验组	样本量：	19
Group：	Experimental group	Sample size：	19
干预措施：	OTR-奥施康定	干预措施代码：
Intervention：	OTR-OXY	Intervention code：

组别：	对照组	样本量：	19
Group：	control group	Sample size：	19
干预措施：	奥施康定-OTR	干预措施代码：
Intervention：	OXY-OTR	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	成都	市(区县)：
Country：	China	Province：	Chengdu	City：
单位(医院)：	四川大学华西医院	单位级别：	三级甲等
Institution hospital：	West China Hospital,Sichuan University	Level of the institution：	Tertiary A hospital

测量指标：

Outcomes：

指标中文名：	血药浓度	指标类型：	主要指标
Outcome：	plasma drug concentration	Type：	Primary 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：

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）：

由数据管理部门使用RAS系统进行随机。

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

Randomisationwas completed using a RAS system by the Sponsor.

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：	Not stated
Blinding：	Not stated

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）：	中国国家药品监督管理局网站http://samr.saic.gov.cn/，公开日期参照国家相关法规
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	China FDA website, http://samr.saic.gov.cn/，according to China administrative regulation
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：	数据管理采用EDC系统
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Electronic Data Capture, EDC
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2018-07-19 12:01:04