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：	ChiCTR1800018599
最近更新日期： Date of Last Refreshed on：	2018-09-26 17:56:15
注册时间： Date of Registration：	2018-09-26 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	Bioequivalence study of Risperidone in patients with schizophrenia or bipolar I disorder
Public title：	Bioequivalence study of Risperidone in patients with schizophrenia or bipolar I disorder
注册题目简写：
English Acronym：
研究课题的正式科学名称：	Bioequivalence study of Risperidone in patients with schizophrenia or bipolar I disorder
Scientific title：	Bioequivalence study of Risperidone in patients with schizophrenia or bipolar I disorder
研究课题代号(代码)： Study subject ID：	Protocol Number: CBCC/2018/002, Version 1.0, dated 07/Jun/2018
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：	The Clinical Trials Registry- India: CTRI/2018/09/015704

申请注册联系人：	Dr. Sandeep Singh	研究负责人：	Dr. Sandeep Singh
Applicant：	Dr. Sandeep Singh	Study leader：	Dr. Sandeep Singh
申请注册联系人电话： Applicant telephone：	+91- 9637555304	研究负责人电话： Study leader's telephone：	+91- 9637555304
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：	sandeep.singh@cbcc.global	研究负责人电子邮件： Study leader's E-mail：	sandeep.singh@cbcc.global
申请单位网址(自愿提供)： Applicant website(voluntary supply)：	www.cbcc.global	研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：	www.cbcc.global
申请注册联系人通讯地址：	Second Floor, Skoda House, Opposite L J Campus, S G Highway, Sarkhej, Ahmadabad, Gujarat, India	研究负责人通讯地址：	Second Floor, Skoda House, Opposite L J Campus, S G Highway, Sarkhej, Ahmadabad, Gujarat, India
Applicant address：	Second Floor, Skoda House, Opposite L J Campus, S G Highway, Sarkhej, Ahmadabad, Gujarat, India	Study leader's address：	Second Floor, Skoda House, Opposite L J Campus, S G Highway, Sarkhej, Ahmadabad, Gujarat, India
申请注册联系人邮政编码： Applicant postcode：	382210	研究负责人邮政编码： Study leader's postcode：	382210
申请人所在单位：	印度CBCC全球临床研究合同组织
Applicant's institution：	CBCC Global Research LLP India
研究负责人所在单位：	印度CBCC全球临床研究合同组织
Affiliation of the Leader：	CBCC Global Research LLP India

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：	3	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：	Kanoria Ethics Committee
Name of the ethic committee：	Kanoria Ethics Committee
伦理委员会批准日期： Date of approved by ethic committee：	2018-08-06 00:00:00
伦理委员会联系人：	Dr. Vipul Dave
Contact Name of the ethic committee：	Dr. Vipul Dave
伦理委员会联系地址：	Kanoria Hospital and Research Center, Airport-Gandhinagar Highway, Village Bhat, District Gandhinagar - 382428, Gujarat, India
Contact Address of the ethic committee：	Kanoria Hospital and Research Center, Airport-Gandhinagar Highway, Village Bhat, District Gandhinagar - 382428, Gujarat, India
伦理委员会联系人电话： Contact phone of the ethic committee：	+91-93271 58957	伦理委员会联系人邮箱： Contact email of the ethic committee：	kanoria.ec@gmail.com

研究实施负责（组长）单位：

齐鲁制药有限公司/印度CBCC全球临床研究合同组织

Primary sponsor：

Qilu Pharmaceutical Co.,Ltd/CBCC Global Research LLP India

研究实施负责（组长）单位地址：

中国山东济南高新技术区

Primary sponsor's address：

317 Xinluo Road, High-Tech Zone, Ji'nan, Shandong, China 250100

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	山东	市(区县)：
Country：	China	Province：	Shandong	City：	Jinan
单位(医院)：	齐鲁制药有限公司	具体地址：	中国山东济南高新技术区
Institution hospital：	Qilu Pharmaceutical Co.,Ltd	Address：	317 Xinluo Road, High-Tech Zone

经费或物资来源：

齐鲁制药有限公司

Source(s) of funding：

Qilu Pharmaceutical Co.,Ltd

研究疾病：

精神分裂症或双极性I型障碍

Target disease：

Schizophrenia or Bipolar I Disorder

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：

探索性研究/预试验

Study phase：

0

研究设计：

随机交叉对照

Study design：

Cross-over

研究目的：

Primary Objective: To assess the steady-state bioequivalence of Risperidone Long-acting intramuscular injection of Qilu Pharmaceuticals Co. Ltd. with RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION of Janssen Pharmaceuticals, Inc. Titusville, NJ 08560 in patients with schizophrenia or bipolar I disorder who are already receiving a stable regimen of Risperidone long-acting injection via the intramuscular route. Secondary Objective: To monitor the adverse events and to ensure the safety of Patients.

Objectives of Study：

Primary Objective: To assess the steady-state bioequivalence of Risperidone Long-acting intramuscular injection of Qilu Pharmaceuticals Co. Ltd. with RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION of Janssen Pharmaceuticals, Inc. Titusville, NJ 08560 in patients with schizophrenia or bipolar I disorder who are already receiving a stable regimen of Risperidone long-acting injection via the intramuscular route. Secondary Objective: To monitor the adverse events and to ensure the safety of Patients.

药物成份或治疗方案详述：

Patients with Schizophrenia or Bipolar I disorder and are already receiving Risperidone long-acting injection at a dose of 25 mg/vial via the intramuscular route every two weeks and have completed at least 2 doses prior to randomization, meeting the above mentioned inclusion and exclusion criteria will be identified. Shortlisted patients will undergo screening not before 28 days of 1st dosing. Patients will be screened on the basis of Demographics, Physical examination including vital signs, Orthostatic hypotension, Medical history, medication history, ECG, Serum Pregnancy test (only for females), hematology, biochemistry, serology and Urine analysis. Upon randomization, patients will receive assigned investigational product at a dose of 25 mg (either A or B) based on the randomization schedule via intramuscular route at the gluteal site on Day 1, 15, 29, 43, 57 and 71 in Period 01 and on Day 85, 99, 113, 127, 141 and 155 in Period 02 at study site. Patients will report to the study site in the evening on day 70 (Period 01), day 112 (Period 02) and day 154 (Period 02) for hospitalization. Patients will be discharged after the collection of 12.00 hours post-dose PK sample on day 71 (Period 01), day 113 (Period 02) and day 155 (period 02). For each subject, total of Fifty five (55) blood PK samples of 3.0mL each will be collected in the study as mentioned in the PK sample collection section. Patients will report to the study site for ambulatory blood PK sample collection on day 2, 3, 4, 5, 7, 9, 11, 13, 16, 17, 18, 19, 21, 23, 25, 27, 72, 73, 74, 75, 77, 79, 81 and 83 in Period 01 and on day 114, 115, 116, 117, 119, 121, 123, 125, 156, 157, 158, 159, 161, 163, 165 and 167 in Period 02. Patients will report to the study site on Day 185±10 for safety follow up.

Description for medicine or protocol of treatment in detail：

Patients with Schizophrenia or Bipolar I disorder and are already receiving Risperidone long-acting injection at a dose of 25 mg/vial via the intramuscular route every two weeks and have completed at least 2 doses prior to randomization, meeting the above mentioned inclusion and exclusion criteria will be identified. Shortlisted patients will undergo screening not before 28 days of 1st dosing. Patients will be screened on the basis of Demographics, Physical examination including vital signs, Orthostatic hypotension, Medical history, medication history, ECG, Serum Pregnancy test (only for females), hematology, biochemistry, serology and Urine analysis. Upon randomization, patients will receive assigned investigational product at a dose of 25 mg (either A or B) based on the randomization schedule via intramuscular route at the gluteal site on Day 1, 15, 29, 43, 57 and 71 in Period 01 and on Day 85, 99, 113, 127, 141 and 155 in Period 02 at study site. Patients will report to the study site in the evening on day 70 (Period 01), day 112 (Period 02) and day 154 (Period 02) for hospitalization. Patients will be discharged after the collection of 12.00 hours post-dose PK sample on day 71 (Period 01), day 113 (Period 02) and day 155 (period 02). For each subject, total of Fifty five (55) blood PK samples of 3.0mL each will be collected in the study as mentioned in the PK sample collection section. Patients will report to the study site for ambulatory blood PK sample collection on day 2, 3, 4, 5, 7, 9, 11, 13, 16, 17, 18, 19, 21, 23, 25, 27, 72, 73, 74, 75, 77, 79, 81 and 83 in Period 01 and on day 114, 115, 116, 117, 119, 121, 123, 125, 156, 157, 158, 159, 161, 163, 165 and 167 in Period 02. Patients will report to the study site on Day 185±10 for safety follow up.

纳入标准：

The patients will be considered eligible for the study based on the following criteria: 
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements;
2. Patient aged 18-65 years (both inclusive) having Body Mass Index (BMI) between 17.00 and 30.00 (both inclusive) calculated as weight in kg/height in m2;
3. Patients with diagnosis of Schizophrenia or Bipolar I Disorder as per DSM-IV-TR criteria or later;
4. Patients receiving Risperidone long-acting injection at a dose of 25mg/vial via the intramuscular route and have completed at least 2 doses prior to randomization;
5. Acceptable hematology status: 
(1) Hemoglobin ≥ 9 g/dL;
(2) Absolute neutrophil count (ANC) ≥ 1500 cells/μL;
(3) Platelet count ≥ 100,000 cells/μL;
6. Acceptable liver function: 
(1) Alanine aminotransferase (ALT) ≤ 2X upper limit of normal (ULN); 
(2) Aspartate aminotransferase (AST) ≤ 2X ULN;
(3) Bilirubin < 1.2 mg/dL;
(4) Alkaline phosphatase ≤ 2X ULN;
7. Patients with Creatinine clearance ≥ 60 mL/minute;
8. Female patients with negative urine pregnancy test on admission day and serum pregnancy test at screening;
9. Females of child bearing potential must be willing to use adequate contraception (as defined below) throughout the study and continuing for at least 3 months after the last dose of the investigational product. For this study, acceptable and effective methods of contraception for females include: 
(1) Intrauterine device placed at least 3 months prior to the start of the study and remaining in place during the study period;
(2) Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom); or 
(3) Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner). 
10. For male patients, one of the following must apply in order to avoid impregnating a female partner, from the first study dose and agree to follow throughout the study and for at least 3 months following the last dose of the study:
(1) Absolute sexual abstinence (no sexual intercourse or genital contact with a female partner);
(2) Use of barrier method with spermicide;
11. No history of addiction to any recreational drug or drug dependence or alcohol addiction.

Inclusion criteria

The patients will be considered eligible for the study based on the following criteria: 
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements;
2. Patient aged 18-65 years (both inclusive) having Body Mass Index (BMI) between 17.00 and 30.00 (both inclusive) calculated as weight in kg/height in m2;
3. Patients with diagnosis of Schizophrenia or Bipolar I Disorder as per DSM-IV-TR criteria or later;
4. Patients receiving Risperidone long-acting injection at a dose of 25mg/vial via the intramuscular route and have completed at least 2 doses prior to randomization;
5. Acceptable hematology status: 
(1) Hemoglobin ≥ 9 g/dL;
(2) Absolute neutrophil count (ANC) ≥ 1500 cells/μL;
(3) Platelet count ≥ 100,000 cells/μL;
6. Acceptable liver function: 
(1) Alanine aminotransferase (ALT) ≤ 2X upper limit of normal (ULN); 
(2) Aspartate aminotransferase (AST) ≤ 2X ULN;
(3) Bilirubin < 1.2 mg/dL;
(4) Alkaline phosphatase ≤ 2X ULN;
7. Patients with Creatinine clearance ≥ 60 mL/minute;
8. Female patients with negative urine pregnancy test on admission day and serum pregnancy test at screening;
9. Females of child bearing potential must be willing to use adequate contraception (as defined below) throughout the study and continuing for at least 3 months after the last dose of the investigational product. For this study, acceptable and effective methods of contraception for females include: 
(1) Intrauterine device placed at least 3 months prior to the start of the study and remaining in place during the study period;
(2) Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom); or 
(3) Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner). 
10. For male patients, one of the following must apply in order to avoid impregnating a female partner, from the first study dose and agree to follow throughout the study and for at least 3 months following the last dose of the study:
(1) Absolute sexual abstinence (no sexual intercourse or genital contact with a female partner);
(2) Use of barrier method with spermicide;
11. No history of addiction to any recreational drug or drug dependence or alcohol addiction.

排除标准：

The patients will be excluded from the study based on the following criteria:
1. Hypersensitivity to Risperidone or Paliperidone or to any of the excipients;
2. Have current thoughts of suicide (suicidal ideation) or violent tendencies at the time of screening;
3. History or presence of neuroleptic malignant syndrome (NMS), tardive dyskinesia, dementia-related psychosis, Parkinsons disease or epilepsy/seizures;
4. Patients with positive urine screen for Drug of Abuse;
5. Patients who are on active treatment with drugs that are known to interact with risperidone (such as Strong CYP2D6 inhibitors, CYP3A4 enzyme inducers);
6. Smokers who smokes greater than or equal to 10 cigarettes or equivalent per day;
7. Patients on different antipsychotic treatment;
8. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product;
9. Surgical or other non-healing wounds;
10. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV);
11. Uncontrolled diabetes mellitus;
12. An unusual or abnormal diet, for whatever reason planned e.g. religious fasting during the course of the study.
13. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study that would limit adherence to study requirements;
14. Participation in any clinical study within 90 days before the first dose of Investigational Product;
15. Donation and/or loss of 350 mL (1 unit) of blood within 90 days prior to first dose of Investigational Product for the current study;
16. Patient is currently Pregnant or breastfeeding.

Exclusion criteria：

The patients will be excluded from the study based on the following criteria:
1. Hypersensitivity to Risperidone or Paliperidone or to any of the excipients;
2. Have current thoughts of suicide (suicidal ideation) or violent tendencies at the time of screening;
3. History or presence of neuroleptic malignant syndrome (NMS), tardive dyskinesia, dementia-related psychosis, Parkinsons disease or epilepsy/seizures;
4. Patients with positive urine screen for Drug of Abuse;
5. Patients who are on active treatment with drugs that are known to interact with risperidone (such as Strong CYP2D6 inhibitors, CYP3A4 enzyme inducers);
6. Smokers who smokes greater than or equal to 10 cigarettes or equivalent per day;
7. Patients on different antipsychotic treatment;
8. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product;
9. Surgical or other non-healing wounds;
10. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV);
11. Uncontrolled diabetes mellitus;
12. An unusual or abnormal diet, for whatever reason planned e.g. religious fasting during the course of the study.
13. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study that would limit adherence to study requirements;
14. Participation in any clinical study within 90 days before the first dose of Investigational Product;
15. Donation and/or loss of 350 mL (1 unit) of blood within 90 days prior to first dose of Investigational Product for the current study;
16. Patient is currently Pregnant or breastfeeding.

研究实施时间：

Study execute time：

从 From 2018-03-27 00:00:00至 To 2019-07-17 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2018-09-30 00:00:00 至 To 2018-10-30 00:00:00

干预措施：

Interventions：

组别：	Group 1	样本量：	12
Group：	Group 1	Sample size：	12
干预措施：	Risperidone Long-acting intramuscular injection of Qilu Pharmaceuticals Co. Ltd.	干预措施代码：
Intervention：	Risperidone Long-acting intramuscular injection of Qilu Pharmaceuticals Co. Ltd.	Intervention code：

组别：	Group 2	样本量：	12
Group：	Group 2	Sample size：	12
干预措施：	RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION of Janssen Pharmaceuticals	干预措施代码：
Intervention：	RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION of Janssen Pharmaceuticals	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	印度	省(直辖市)：	古吉拉特	市(区县)：	甘地加尔
Country：	India	Province：	Gujarat	City：	Gandhinagar
单位(医院)：	Kanoria Hospital & Research Centre	单位级别：	Multispecialty Hospital
Institution hospital：	Kanoria Hospital & Research Centre	Level of the institution：	Multispecialty Hospital

国家：	印度	省(直辖市)：	古吉拉特	市(区县)：	艾哈迈达巴德
Country：	India	Province：	Gujarat	City：	Ahmedabad
单位(医院)：	Bodyline Hospital	单位级别：	Multispecialty Hospital
Institution hospital：	Bodyline Hospital	Level of the institution：	Multispecialty Hospital

国家：	印度	省(直辖市)：	古吉拉特	市(区县)：	朱纳加德
Country：	India	Province：	Gujarat	City：	Junagadh
单位(医院)：	Shri Hatkesh Healthcare Foundation	单位级别：	Multispecialty Hospital
Institution hospital：	Shri Hatkesh Healthcare Foundation	Level of the institution：	Multispecialty Hospital

测量指标：

Outcomes：

指标中文名：	To establish bioequivalence between Risperidone Long-acting intramuscular injection 25 mg/vial of Qilu Pharmaceuticals Co. Ltd. And RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION 25 mg/vial of Janssen Pharmaceuticals, Inc. Titusville, NJ 08560	指标类型：	主要指标
Outcome：	To establish bioequivalence between Risperidone Long-acting intramuscular injection 25 mg/vial of Qilu Pharmaceuticals Co. Ltd. And RISPERDAL CONSTA? (Risperidone) LONG-ACTING INJECTION 25 mg/vial of Janssen Pharmaceuticals, Inc. Titusville, NJ 08560	Type：	Primary indicator
测量时间点：	The pre-dose blood sample (00.00) will be drawn within 10 minutes prior to the scheduled dosing time on day 1, 43, 57 and 71 in Period 01 and on day 113, 141 and 155 in Period 02. Post-dose blood samples after investigational product administration on day 1 and 15: 24.00, 48.00, 72.00,	测量方法：	PK Sample Collection
Measure time point of outcome：	The pre-dose blood sample (00.00) will be drawn within 10 minutes prior to the scheduled dosing time on day 1, 43, 57 and 71 in Period 01 and on day 113, 141 and 155 in Period 02. Post-dose blood samples after investigational product administration on day 1 and 15: 24.00, 48.00, 72.00,	Measure method：	PK Sample Collection

指标中文名：	To monitor the adverse events and to assess safety of patients	指标类型：	次要指标
Outcome：	To monitor the adverse events and to assess safety of patients	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：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	65	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）：

Computer Generated Randomization

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

Computer Generated Randomization

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：	未说明
Blinding：	Not stated
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

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）：	Clinical Study Report
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	Clinical Study Report
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：	An Electronic Data Capture
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	An Electronic Data Capture
数据与安全监察委员会： Data and Safety Monitoring Committee：	无/No
注册人： Name of Registration：	2018-09-26 17:51:59