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CTRI Number  CTRI/2019/06/019832 [Registered on: 25/06/2019] Trial Registered Prospectively
Last Modified On: 18/10/2021
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Generic drug trial seeking for approval of generic paliperidone 1 month injection for treatment of Schizophrenia. 
Scientific Title of Study   A Pivotal, Multiple-Dose, Pharmacokinetic Bioequivalence Trial Comparing Generic to Reference Medicinal Product of Paliperidone Palmitate Prolonged-Release Injectable Suspension (100 mg) in Subjects with Schizophrenia  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
TOL3033B, Version 3.0, Version Date 01/Apr/2019  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sandeep Singh 
Designation  Director Operations 
Affiliation  CBCC Global Research LLP 
Address  Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House Opposite L J Campus S G Highway Sarkhej Ahmedabad – 382210

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Sandeep Singh 
Designation  Director Operations 
Affiliation  CBCC Global Research LLP 
Address  Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House Opposite L J Campus S G Highway Sarkhej Ahmedabad – 382210

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Details of Contact Person
Public Query
 
Name  Dr Sandeep Singh 
Designation  Director Operations 
Affiliation  CBCC Global Research LLP 
Address  Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House Opposite L J Campus S G Highway Sarkhej Ahmedabad – 382210

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Source of Monetary or Material Support
Modification(s)  
Tolmar International Ltd., 14/15 Lower Camden Street, Dublin 2, D02 R9P27, Ireland. 
 
Primary Sponsor
Modification(s)  
Name  Tolmar International Ltd 
Address  Tolmar International Ltd., 14/15 Lower Camden Street, Dublin 2, D02 R9P27, Ireland. 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NA  NA 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 13  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Vikharam Ramasubramanian  Ahana Hospitals  4th floor, Clinical Research Room, Ahana Hospitals, No.11, Subburaman Street, Gandhinagar, Madurai-625020
Madurai
TAMIL NADU 
9677725588

vikhram@ahanahospitals.in 
Dr Rajendra Someshwar Anand  Anand Multispecialty Hospital & Research Center  4th floor, sarthak Mall, Mahatma Mandir road, Sargasan Cross road, Gandhinagar-382421
Gandhinagar
GUJARAT 
9724017700

drrajendraanand@yahoo.com 
Dr Timirkumar Chandrakant Shah  Divyam Hospital  3rd Floor, Research Room, Divyam Hospital, Block no 84, Palsana Cross road, National Highway No: 8, Palsana, Surat-394315
Surat
GUJARAT 
9825137443

drtcshah@gmail.com 
Dr Sarika Dakshikar  Gokuldas Tejpal Hospital  1st floor, Department of Psychiatry, Gokuldas Tejpal Hospital, Grant Govt Medical college & Sir J.J. group of Hospitals, Mumbai-400001
Mumbai
MAHARASHTRA 
9819970710

sarikadakshikar@gmail.com 
Dr Bakul Chandrakant Buch  Hatkesh Healthcare Foundation  2nd Floor, Research Room , Hatkesh Healthcare foundation, Saraswati Mandir complex, Nr Bhutnath Temple, Near Domadiya Vadi, college Rd, Junagadh-362001
Junagadh
GUJARAT 
9825220330

bakulbuch@gmail.com 
Dr Dalaya Nitin Veersingh  Life Point Multispecialty Hospital  3rd Floor, Research Department, Life point Multispecialty Hospital, 145/1 Mumbai-Bangalore Highway, Near Hotel Sayaji, Wakad, Pune-411057
Pune
MAHARASHTRA 
9552503210

drndalaya@gmail.com 
Dr Poorav Rameshchandra Patel  Medistar Multispecialty Hospital  3rd Floor, Research Department, Medistar Multispecialty Hospital, Trimurti Avenue, Medistar Cross Road, NH-08, Industrial area, Himmatnagar-383001
Sabar Kantha
GUJARAT 
9428772609

drpoorav_patel@gmail.com 
Dr Tarak Shah  MITR Foundation  1st Floor, Research Room, MITR Foundation, 1 Shantinagar Society, Way to CCD gully, Usmanpura, Ashram Road, Ahmedabad-380013
Ahmadabad
GUJARAT 
9824096430

tarak_mitr@yahoo.co.in 
Dr Radhika Reddy  Old Govt. General Hospital  2nd floor, Clinical Research Room, Old Govt. General hospital (associated by Siddhartha Medical college), Hanuman pet, Two town, Vijaywada-520002
Krishna
ANDHRA PRADESH 
9848229798

rrvemireddy@yahoo.com 
Dr Kulkarni Krishnaji Siddo  Oyster & Pearl Hospitals  4th Floor, O & P Research Room, Oyster and Pearl Hospital, room No 504, 1671-75 Ganeshkhind road, Near Hotel Pride, Shivajinagar, Pune- 411005
Pune
MAHARASHTRA 
9657890464

omksk54@gmail.com 
Dr Vaishal Nareshchandra vora  Ratandeep Multispecialty Hospital  5th Floor, Clinical Research Department, Ratandeep Multispeciality Hospital, 5th floor Nakshtra Complex, above HDFC Bank, Maninagar Cross Road, Maninagar, Ahmedabad-380008
Ahmadabad
GUJARAT 
9825440891

vnvora@gmail.com 
Dr R Sathianathan  Sri Ramchandra Institute of Higher Education and Research (SRIHER)  Basement, Clinical Research Room, Dental Hospital Building, Sri Ramchandra Institute of higher education and research, no 1 Ramchandra Nagar, Porur, Chennai-600116
Chennai
TAMIL NADU 
9841019910

sathianathen6@yahoo.com 
Dr Kalrav Mistry  Svayambhu Hospital  Research Department, First Floor, Opposite RAF camp, SP ring road, vastral, Ahmedabad- 382418, India.
Ahmadabad
GUJARAT 
9904010448

spin2kalrav@yahoo.co.in 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 13  
Name of Committee  Approval Status 
Anand Ethics Committee  Approved 
Ethics Committee MITR Foundation  Approved 
Ethics Committee, Hatkesh Heatlthcare Foundation  Approved 
Ethics Committee, Radianz Health Care and Research  Approved 
Ethics Committee, Ratandeep Multispecialty hospital  Approved 
Institutional Ethics Committee, Divyam Hospital  Approved 
Institutional Ethics Committee, Grant Govt. Medical College & Sir J.J Group of Hospital  Approved 
Institutional Ethics Committee, Siddhartha Medical College & Govt. General Hospital (IEC SMC & CGH)  Approved 
Institutional Ethics Committee, Sri Ramachandra University  Approved 
LPR Ethics Committee  Approved 
Medistar Hospital Ethics Committee  Approved 
O & P Institutional Ethics Committee  Approved 
Svayambu Hospital Ethics Commiittee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: F209||Schizophrenia, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Reference Product   Xeplion® 100 mg prolonged release suspension for injection (Janssen-Cilag International NV; hereinafter referred to as Xeplion)  
Intervention  Test Product   Paliperidone Palmitate Prolonged-Release Injectable Suspension (PP-PRIS; Tolmar)  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Able to understand the investigational nature of this study and provide written informed consent prior to the participation in the trial
2.Subjects between 18 and 65 years of age (both inclusive)
3. Subjects having body mass index (BMI) between 18.50 to 30.00 kg/m2 (both inclusive)
4. Subjects diagnosed with schizophrenia as per DSM-IV-TR (or later) criteria.
5. Acceptable hematology status:
a. Hemoglobin ≥ 9 g/dL
b. Absolute neutrophil count (ANC) ≥ 1500 cells/μL
c. Platelet count ≥ 100,000 cells/μL
6. Acceptable liver function:
a. Alanine aminotransferase (ALT) ≤ 2X upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) ≤ 2X ULN
c. Bilirubin < 1.2 mg/dL
d. Alkaline phosphatase ≤ 2X ULN
7. Subjects with creatinine clearance ≥ 80 mL/minute
8. Female subjects with negative serum pregnancy test at screening.
9. Subjects who agree to use adequate contraception (e.g., hormonal, chemical, double-barrier, or abstinence) while in the study and for 3 months after study participation is discontinued
10. No history of addiction to any recreational drug or drug dependence or alcohol addiction within 12 months prior to randomization
11. Must be able to attend regularly scheduled study center appointments and be able to abide by all study requirements
 
 
ExclusionCriteria 
Details  1. Hypersensitivity to paliperidone palmitate or risperidone or to any of the excipients of the formulations
2. Subjects who are in an acutely agitated or severely psychotic state
3. Subjects who have current thoughts of suicide (suicidal ideation) or violent tendencies at the time of screening
4. Subjects who have a Rating of >4 (moderately ill) on the CGI-S scale at screening
5. History or presence of neuroleptic malignant syndrome (NMS), tardive dyskinesia, dementia-related psychosis, Parkinson’s disease or epilepsy/seizures
6. History or presence of any uncontrolled debilitating systemic disease (e.g., cardiovascular disease, hypertension, diabetes mellitus etc.)
7. Current or anticipated use during study participation of any of the prohibited medications. (See Appendix 14.1)
8. Subjects with congenital long QT syndrome (QTc of > 470 msec for females and > 450 msec for males) or presence of severe cardiovascular disease defined as having required cardiovascular surgery or the occurrence of incapacitating myocardial infarction within past 12 months
9.Subjects with history of arrhythmia
10. Subjects with positive urine screen for drugs of abuse (Except for benzodiazepine which is a permissible medication supported by prescription)
11. Smokers who smoke ≥ 10 cigarettes or equivalent per day
12. Major surgical procedure (including periodontal) within 28 days of first IP dosing
13. Current surgical or other non-healing wounds
14. Subjects with positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
15. 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 or that could limit adherence to study requirements
16. Participation in any clinical study within 90 days of first IP dosing
17. Donation and/or loss of ≥ 350 mL (1 unit) of blood within 90 days of first IP dosing
18. Lactating women
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Pre-numbered or coded identical Containers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To establish the multiple dose steady-state bioequivalence of equivalent doses of TEST [PP-PRIS 100 mg (Tolmar)] and RMP [Xeplion 100 mg (Janssen-Cilag International NV)]   Pre-dose blood sample(within 5minutes prior to dosing)- Day:1,85(Dose-4),113 (Dose-5),141 (Dose-6); Day 142 24 hours; Day 143 48 hours,Day 144 72 hours,Day 145 96 hours(± 60 minutes).Day 146-120 hours, Day 147-144 hours, Day 148-168 hours, Day 149-192 hours, Day 150-216 hours, Day 151-240 hours, Day 152-264 hours, Day 154-312 hours, Day 156-360 hours, Day 158-408 hours, Day 161-480 hours, Day 165-576 hours, Day 169-672 hours (±4 hours)  
 
Secondary Outcome  
Outcome  TimePoints 
To assess safety and tolerability of RMP and TEST in subjects who are exposed to the investigational product (IP; either TEST or RMP).   Pre-dose blood sample(within 5minutes prior to dosing)- Day:1,85(Dose-4),113 (Dose-5),141 (Dose-6); Day 142 24 hours; Day 143 48 hours,Day 144 72 hours,Day 145 96 hours(± 60 minutes).Day 146-120 hours, Day 147-144 hours, Day 148-168 hours, Day 149-192 hours, Day 150-216 hours, Day 151-240 hours, Day 152-264 hours, Day 154-312 hours, Day 156-360 hours, Day 158-408 hours, Day 161-480 hours, Day 165-576 hours, Day 169-672 hours (±4 hours) 
 
Target Sample Size   Total Sample Size="320"
Sample Size from India="320" 
Final Enrollment numbers achieved (Total)= "296"
Final Enrollment numbers achieved (India)="296" 
Phase of Trial   N/A 
Date of First Enrollment (India)   01/07/2019 
Date of Study Completion (India) 19/08/2020 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="2"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   None 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

The Study is A Pivotal, Multiple-Dose, Pharmacokinetic Bioequivalence Trial Comparing Generic to Reference Medicinal Product of Paliperidone Palmitate Prolonged-Release Injectable Suspension (100 mg) in Subjects with Schizophrenia

Primary Objective: To establish the multiple dose steady-state bioequivalence of equivalent doses of TEST [PP-PRIS 100 mg (Tolmar)] and RMP [Xeplion 100 mg (Janssen-Cilag International NV)]

Secondary Objective: To assess safety and tolerability of RMP and TEST in subjects who are exposed to the investigational product (IP; either TEST or RMP).

 

 
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