ChiCTR2500098127 版本V1.0 版本创建时间2025/03/03 16:03:48 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：

 ChiCTR2500098127 

最近更新日期：

Date of Last Refreshed on：

 2025-03-03 16:03:26 

注册时间：

Date of Registration：

 2025-03-03 00:00:00 

注册号状态：

补注册

Registration Status：

Retrospective registration

注册题目：

氨酚羟考酮片人体生物等效性试验

Public title：

Bioequivalence study of acetaminophen and oxycodone tablets in humans

注册题目简写：

English Acronym：

研究课题的正式科学名称：

氨酚羟考酮片人体生物等效性试验

Scientific title：

Bioequivalence test of acetaminophen and oxycodone tablets in humans

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：

邱博 

研究负责人：

宋浩静 

Applicant：

Qiu Bo 

Study leader：

Song Haojing 

申请注册联系人电话：

Applicant telephone：

 +86 134 8342 0159

研究负责人电话：

Study leader's
telephone：

+86 180 3373 6090

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：

 qiubo47@126.com

研究负责人电子邮件：

Study leader's E-mail：

 lcsydzj@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：

河北省石家庄市新华区和平西路348号

研究负责人通讯地址：

河北省石家庄市新华区和平西路348号

Applicant address：

348 Heping Road West, Xinhua District, Shijiazhuang, Hebei,China

Study leader's address：

348 Heping Road West, Xinhua District, Shijiazhuang, Hebei,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：

河北省人民医院

Applicant's institution：

Hebei General Hospital

研究负责人所在单位：

河北省人民医院

Affiliation of the Leader：

Hebei General Hospital

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：

 (2024)药伦审第(16-01)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：

河北省人民医院医学伦理委员会

Name of the ethic committee：

The Ethics Committee of Hebei General Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2024-04-03 00:00:00

伦理委员会联系人：

鲁杨

Contact Name of the ethic committee：

Lu Yang

伦理委员会联系地址：

河北省石家庄市新华区和平西路348号

Contact Address of the ethic committee：

348 Heping Road West, Xinhua District, Shijiazhuang, Hebei,China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 311 8598 8311

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：

河北省人民医院

Primary sponsor：

Hebei General Hospital

研究实施负责（组长）单位地址：

河北省石家庄市新华区和平西路348号

Primary sponsor's address：

348 Heping Road West, Xinhua District, Shijiazhuang, Hebei,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)：

河北省

市(区县)：

新乐市

Country：

China

Province：

Hebei province

City：

单位(医院)：

河北奥星集团药业有限公司

具体地址：

河北省新乐市南环东路1号

Institution
hospital：

HEBEI AOXING GROUP PHARMACEUTICAL CO..LTD

Address：

No. 1, Nanhuan East Road, Xinle City, Hebei Province

经费或物资来源：

河北奥星集团药业有限公司

Source(s) of funding：

Hebei Aoxing Group Pharmaceutucal CO.LTD

研究疾病：

无  

Target disease：

NA

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：

本研究以河北奥星集团药业有限公司生产的氨酚羟考酮片（规格：盐酸羟考酮5mg和对乙酰氨基酚325mg）为受试制剂，以远藤制药有限公司（Endo Pharmaceuticals Inc）持证帕尔医药公司（Par Pharmaceutical）生产的氨酚羟考酮片(商品名：PERCOCET?，规格：盐酸羟考酮5mg和对乙酰氨基酚325mg)为参比制剂，评价在空腹/餐后条件下口服两种制剂的生物等效性。  

Objectives of Study：

In this study, acetaminophen and oxycodone tablets (Specifications: Oxycodone hydrochloride 5mg and acetaminophen 325mg) were test preparations, acetaminophen oxycodone tablets (PERCOCET?, Endo Pharmaceuticals Inc., licensed Par Pharmaceutical, Specifications: Oxycodone hydrochloride 5mg and acetaminophen 325mg) were used as reference formulations to evaluate the bioequivalence of the two formulations administered orally under fasting/postprandial conditions.

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）18周岁以上（含18周岁）的健康受试者，男女均有； 2）男性体重≥50.0kg，女性体重≥45.0kg，且体重指数（BMI）在19.0至26.0kg/m^2（含19.0和26.0）范围内（BMI=体重/身高^2）； 3）研究期间以及在末次研究药物给药后至少6个月内无生育计划，自愿采取有效避孕措施且无捐精或捐卵计划； 4）能与研究者进行良好的沟通，理解和遵守本项研究的各项要求，并自愿签署知情同意书。

Inclusion criteria

1. Healthy subjects over 18 years old, both male and female; 2. body weight >=50.0kg for men and >=45.0kg for women with body mass index (BMI) between 19.0 and 26.0kg/m^2 (including 19.0 and 26.0kg/m2) (BMI= weight/height^2); 3. have no plans to have children during the study and for at least 6 months after the last dose of study drug, voluntarily use effective contraceptive methods, and have no plans to donate sperm or eggs; 4. Able to communicate well with the investigators, understand and comply with the requirements of this study, and sign the informed consent voluntarily.

排除标准：

1）筛选前3个月内参加了任何药物临床试验者且使用研究药物者，或非本人参加试验； 2）三年内有慢性或活动性消化道疾病如食管疾病、胃炎、胃溃疡十二指肠溃疡、肠炎，活动性胃肠道出血或消化道手术者且研究者认为目前仍有临床意义者；（问诊） 3）有心血管系统、呼吸系统、内分泌系统、泌尿生殖系统、神经系统、精神系统、血液学、免疫学、代谢异常、皮肤骨骼、眼、耳鼻喉等病史且研究者认为目前仍有临床意义者；（问诊） 4）有可待因、氨酚羟考酮过敏史，有变态反应性疾病史、哮喘史；或对已知药物、生物制剂或氨酚羟考酮产品辅料中任何成分过敏史；或过敏体质，或对食物或其他物质过敏史，或有过敏疾病史（如过敏性休克、血管性水肿等），且研究者认为目前仍有临床意义者；（问诊） 5）不能耐受静脉穿剌或采血困难或有晕血、晕针史者；（问诊） 6）既往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；或筛选前3个月内接受过外科手术或进行过活检或有大创伤且研究者判断不宜进入试验者；或计划在研究期间进行外科手术者，或计划在本试验出组后4周内进行手术者；（问诊） 7）筛选前14天内使用过任何药物者（包括中草药、保健品）（问诊）； 8）筛选前30天内使用过任何CYP3A4或P-gp抑制剂（酮康唑、伊曲康唑、伏立康唑、泊沙康唑、氟康唑、红霉素、克拉霉素、决奈达隆、HIV蛋白酶抑制剂（利托那韦）、维拉帕米、地尔硫卓、胺碘酮、环孢素、他克莫司等），或CYP3A4或P-gp诱导剂（利福平、苯妥英、卡马西平、苯巴比妥等），或CYP3A4或P-gp底物（咪达唑仑、地高辛、阿托伐他汀、奥美拉唑、奎尼丁等）者；（问诊） 9）有支气管哮喘、慢性阻塞性肺病、呼吸抑制、高碳酸血症病史者；（问诊） 10）有麻痹性肠梗阻病史者；（问诊） 11）有或既往有习惯性便秘者；有排尿困难，排尿费力，尿流量变细者；（问诊） 12）筛选前7天内排便不规律或恶心呕吐者；（问诊） 13）有长期阿片类药物用药史者，或对阿片类药物有依赖性者；（问诊） 14）有体位性低血压病史者：（问诊） 15）筛选前14天内接种疫苗，或计划会在试验期间接种这些疫苗者； 16）筛选前3个月内献血或大量失血（≥400mL）者，接受输血或使用血制品者，或打算在试验期间或试验结束后3个月内献血或血液成份者； 17）药物滥用者或试验前1年内使用过毒品者，或尿液毒品筛查（吗啡、甲基安非他明、氯胺酮）试验阳性者； 18）嗜烟者或试验前3个月每日吸烟量多于5支者，或试验期间不能停止使用任何烟草类产品者； 19）酗酒者或筛选前6个月内经常饮酒者，即每周饮酒超过14单位酒精（1单位=360mL啤酒或45mL酒精量为40%的烈酒或150mL葡萄酒）；或试验期间不愿意停止饮酒或任何含酒精的制品；或酒精呼气阳性者（数值大于0mg/100mL）； 20）每天饮用茶、咖啡和/或含咖啡因的饮料者，或不同意试验期间停止饮用茶、咖啡和/或含咖啡因的饮料者； 21）在服用研究药物前7天内进食可能影响药物体内代谢的饮食（包括火龙果、芒果、葡萄柚或葡萄柚产品、柚子和/或黄嘌呤饮食，含咖啡因、酒精、尼古丁的食品或饮品），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，或不同意试验期间停止进食上述饮食者； 22）对饮食有特殊要求，不能遵守统一饮食者，或对乳糖不耐受（喝牛奶及奶制品腹泻）者，或吞咽困难者； 23）病毒学检查：乙型肝炎表面抗原阳性、丙型肝炎病毒抗体阳性、人免疫缺陷病毒抗体阳性、梅毒螺旋体抗体阳性、乙肝e抗原阳性； 24）体格检查、心电图、实验室检查、生命体征及各项检查异常有临床意义者（以临床医师判断为准）； 25）女性妊娠检查阳性者；哺乳期女性；女性受试者筛选前30天内使用口服避孕药或筛选前6个月内使用长效雌激素或孕激素注射剂或埋植片者； 26）试验期间不能停止从事高危、高空作业或精密操作、驾驶类职业者或运动员； 27）研究者认为有不适合参加试验的其他因素； 28）受试者因自身原因不能参加试验者。

Exclusion criteria：

1. Participants who participated in any drug clinical trial within 3 months before screening and used the study drug, or did not participate in the trial themselves; 2. patients with chronic or active gastrointestinal diseases such as esophageal disease, gastritis, gastric ulcer, duodenal ulcer, enteritis, active gastrointestinal bleeding, or gastrointestinal surgery within the past three years and still clinically relevant according to the investigator; (for inquiry) 3. medical history of cardiovascular system, respiratory system, endocrine system, genitourinary system, nervous system, mental system, hematology, immunology, metabolic abnormalities, skin and bone, eye, ear, nose and throat, etc. (for inquiry) 4. A history of allergy to codeine, acetaminophen and oxycodone, allergic diseases, and asthma; Or a history of allergy to known drugs, biologics, or any ingredient in paracetamol and oxycodone product excipients; Or allergic constitution, or a history of allergy to food or other substances, or a history of allergic diseases (such as anaphylactic shock, angioedema, etc.), and the investigator believes that it is still clinically relevant; (for inquiry) 5. those who cannot tolerate vein puncture or have difficulty in blood collection, or have a history of syncope or syncope; (for inquiry) 6. patients who have undergone previous surgery that may affect the absorption, distribution, metabolism, and excretion of drugs according to the investigator's judgment; Or patients who had undergone surgery or biopsy within 3 months before screening or had major trauma and were judged by the investigator to be unsuitable for trial entry; If a surgical procedure was planned during the study or within 4 weeks of exit from the trial; (for inquiry) 7. those who had taken any medicine (including Chinese herbal medicine and health supplements) within 14 days before screening (inquiry); 8. use of any CYP3A4 or P-gp inhibitor (ketoconazole, itraconazole, voriconazole, posaconazole, fluconazole, erythromycin, clarithromycin, dronedarone, HIV protease inhibitor (ritonavir), verapamil, diltiazem, amiodarone, cyclosporine, tacrolimus, and others) within 30 days before screening; Or CYP3A4 or P-gp inducers (rifampicin, phenytoin, carbamazepine, phenobarbitone, etc.), or CYP3A4 or P-gp substrates (midazolam, digoxin, atorvastatin, omeprazole, quinidine, etc.); (for inquiry) 9. History of bronchial asthma, chronic obstructive pulmonary disease, respiratory depression, hypercapnia; (for inquiry) 10. history of paralytic ileus; (for inquiry) 11. have or had habitual constipation; Patients with dysuria, difficult urination, and decreased urine flow; (for inquiry) 12. patients with irregular bowel movements or nausea and vomiting within 7 days before screening; (for inquiry) 13. with a long history of opioid use or dependence on opioids; (for inquiry) 14. Patients with a history of orthostatic hypotension: (inquiry) 15. who received a vaccine within 14 days before screening, or who plan to receive one during the trial; 16. those who had donated blood or lost a large amount of blood (≥400mL) within 3 months before screening, received blood transfusion or blood products, or intended to donate blood or blood components during or within 3 months after the trial; 17. drug abusers or had used drugs within 1 year before the test, or had positive urine drug screening test (morphine, methamphetamine, ketamine); 18. smoker or had smoked more than 5 cigarettes per day in the 3 months before the trial, or could not stop using any tobacco products during the trial; 19. were heavy drinkers or regular drinkers in the 6 months before screening, i.e. consumed more than 14 units of alcohol per week (1 unit =360mL of beer or 45mL of 40% spirits or 150 ml of wine); Or unwillingness to stop drinking alcohol or any alcohol-based product during the trial; Or alcohol breath positive (value > 0mg/100mL); 20. who consumed tea, coffee and/or caffeinated beverages daily or who did not agree to stop drinking tea, coffee and/or caffeinated beverages during the trial; 21. consuming diets (including dragon fruit, mango, grapefruit or grapefruit products, grapefruit and/or xanthine diets, foods or drinks containing caffeine, alcohol, or nicotine) within 7 days before taking the study drug, or other diets that the investigators believe may affect the absorption, distribution, metabolism, or excretion of the drug; Or did not agree to stop taking the above diet during the trial; 22. those who have special dietary requirements, cannot follow a uniform diet, or are intolerant to lactose (milk and dairy product diarrhea), or have difficulty swallowing; 23. positive for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, treponema pallidum antibody and hepatitis B e antigen; 24. physical examination, electrocardiogram, laboratory examination, vital signs, and abnormalities of various examinations were clinically significant (subject to clinician's judgment); 25. women with a positive pregnancy test; Women who are lactating; Women who used oral contraceptives within 30 days before screening or long-acting estrogen or progestin injections or implants within 6 months before screening; 26. During the trial, they cannot stop engaging in high-risk, high-altitude work or precision operation, driving or athletes; 27. other factors considered by the investigator to be inappropriate for trial participation; 28. subjects were unable to participate in the trial due to their own reasons.

研究实施时间：

Study execute time：

从 From 2024-05-11 00:00:00至 To 2024-07-12 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2024-05-11 00:00:00 至 To 2024-05-20 00:00:00

干预措施：

Interventions：

组别：

空腹 T-R-T-R组

样本量：

 14

Group：

fasted T- R-T-R group

Sample size：

干预措施：

受试者在空腹状态下，第一周期服用受试制剂，第二周期服用参比制剂，第三周期服用受试制剂，第四周期服用参比制剂

干预措施代码：

Intervention：

The subjects took the test preparation in the first cycle, the reference preparation in the second cycle, the test preparation in the third cycle, and the reference preparation in the fourth cycle under fasting conditions.

Intervention code：

组别：

空腹 R-T-R-T组

样本量：

 14

Group：

fasted R-T-R-T group

Sample size：

干预措施：

受试者在空腹状态下，第一周期服用参比制剂，第二周期服用受试制剂，第三周期服用参比制剂，第四周期服用受试制剂

干预措施代码：

Intervention：

The subjects took the reference preparation in the first cycle, the test preparation in the second cycle, the reference preparation in the third cycle, and the test preparation in the fourth cycle in a fasting state.

Intervention code：

组别：

餐后 T-R-T-R组

样本量：

 20

Group：

postprandial T- R-T-R group

Sample size：

干预措施：

受试者在餐后状态下，第一周期服用受试制剂，第二周期服用参比制剂，第三周期服用受试制剂，第四周期服用参比制剂

干预措施代码：

Intervention：

In the postprandial state, the subjects took the test preparation in the first cycle, the reference preparation in the second cycle, the test preparation in the third cycle, and the reference preparation in the fourth cycle.

Intervention code：

组别：

空腹 R-T-R-T组

样本量：

 20

Group：

postprandial R-T-R-T

Sample size：

干预措施：

受试者在餐后状态下，第一周期服用参比制剂，第二周期服用受试制剂，第三周期服用参比制剂，第四周期服用受试制剂

干预措施代码：

Intervention：

In the postprandial state, the subjects took the reference preparation in the first cycle, the test preparation in the second cycle, the reference preparation in the third cycle, and the test preparation in the fourth cycle.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 河北省 

市(区县)：

  

Country：

China

Province：

Hebei province

City：

单位(医院)：

 河北省人民医院 

单位级别：

 三甲 

Institution
hospital：

Hebei General Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

峰浓度

指标类型：

主要指标

Outcome：

Cmax

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

从0时刻到t时的药时曲线下面积

指标类型：

主要指标

Outcome：

AUC0-t

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

从0时刻到无穷时的药时曲线下面积

指标类型：

主要指标

Outcome：

AUC0-∞

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

达峰时间

指标类型：

次要指标

Outcome：

Tmax

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

消除终末端半衰期

指标类型：

次要指标

Outcome：

t1/2

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

消除速率常数

指标类型：

次要指标

Outcome：

λz

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

残留面积百分比

指标类型：

次要指标

Outcome：

AUC_%Extrap

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：

征募研究对象情况：

Recruiting status：

结束

/Completed

年龄范围：

Participant age：
最小 Min age 19 岁 years
最大 Max age 48 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）：

受试者随机表由统计分析单位的随机统计师负责，采用区组随机的方法，试验设计阶段以SAS V9.4软件制作随机表，将成功入选的受试者按1:1比例，随机分配到2个给药顺序组（T-R-T-R组和R-T-R-T组）之一

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

The randomization list for the subjects was generated by a statistician responsible for randomization at the statistical analysis unit, using stratified randomization. The randomization list was produced using SAS V9.4 software during the trial design phase, and successfully enrolled subjects were randomly assigned to one of two treatment sequences (T-R-T-R group and R-T-R-T group) in a 1:1 ratio.

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：

无

Blinding：

NA

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）：

2024年12月11日之后通过网络平台公开原始数据?：https://study.cims-medtech.com/C003/?uc=C003

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

?Raw data will be made publicly available through web platforms after December 11, 2024:https://study.cims-medtech.com/C003/?uc=C003

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 DAS EDC。 电子病例报告表（eCRF）：数据管理员根据试验方案设计构建，并根据数据核查 计划（DVP）设置逻辑核查，通过测试并获申办方批准后发布使用。 数据录入：eCRF 数据来源于原始记录，由数据录入人员根据 eCRF 填写说明，将 志愿者访视数据及时录入 EDC。 源数据现场核查（SDV）：监查员进行 eCRF 数据与源数据的一致性核对，有问题 可发疑问。 数据疑问和解答：疑问来源于 EDC 逻辑核查的系统疑问，监查员、数据管理员等 人工疑问，研究者需及时解答疑问。数据管理员和监查员进行疑问批复，必要时可 再次发出疑问，直至数据“清洁”。 研究者签名：数据录入完成并经 SDV 后，研究者进行电子签名审核确认。签名后 的如有数据修订，需重新签名。 数据库锁定：由主要研究者、申办者、统计分析人员和数据管理人员共同签署数据 库锁定记录后，数据管理员进行数据库锁定。 数据库提交：数据管理员向统计人员提交数据库。 eCRF 存档：每个志愿者的 eCRF 生成 PDF 电子文档保存。 EDC 关闭：统计分析完成后，数据管理员关闭数据库。

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

This experiment adopts electronic data management and uses DAS EDC. Electronic Case Report Form (eCRF): The data administrator designs and builds according to the trial protocol, and verifies based on the data The plan (DVP) is set up for logical verification, and will be released for use after passing the test and obtaining approval from the sponsor. Data entry: The eCRF data comes from the original record, and the data entry personnel fill in the instructions based on the eCRF to Timely input of volunteer visit data into EDC. On site verification of source data (SDV): The inspector checks the consistency between eCRF data and source data, and there are issues May raise questions. Data Questions and Answers: Questions originate from EDC logic verification system questions, such as auditors, data administrators, etc Artificial questions require researchers to promptly answer them. Data administrators and inspectors can provide feedback on questions, and if necessary Issue the question again until the data is' clean '. Researcher's signature: After the data entry is completed and passed through SDV, the researcher conducts an electronic signature review and confirmation. After signing If there are any data revisions, a new signature is required. Database locking: The data is jointly signed by the main researchers, applicants, statistical analysts, and data management personnel After the database locks the records, the data administrator locks the database. Database submission: The data administrator submits the database to the statistician. ECRF Archive: Each volunteer's eCRF is generated and saved as a PDF electronic document. EDC shutdown: After statistical analysis is completed, the data administrator closes the database.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-03-03 16:03:26