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CTRI Number  CTRI/2018/05/013703 [Registered on: 04/05/2018] Trial Registered Prospectively
Last Modified On: 24/05/2019
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Pharmacokinetic study of two formulations of paliperidone palmitate extended-release injectable suspension in patients with schizophrenia. 
Scientific Title of Study   An Open Label, Randomized, Multicenter, Multiple-dose, Two-treatment, Single-period, Parallel,Steady State Bioequivalence Study of Paliperidone Palmitate Extended-Release Injectable Suspension 156 mg of Mylan Laboratories Limited, India and INVEGA SUSTENNA® (Paliperidone Palmitate) Extended-Release Injectable Suspension 156 mg of Janssen Pharmaceuticals, Inc. Titusville, NJ 08560 in Subjects with Schizophrenia under Fasting Condition. 
Trial Acronym  NA 
Secondary IDs if Any  
Secondary ID  Identifier 
CRL061719, Version 1.0, dated 12-Oct-17  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Dhruv Patel 
Designation  Medical Monitor 
Affiliation  Cliantha Research Limited 
Address  Garden View Corporate House No. 8 Opp. AUDA Garden, Bodakdev, Ahmedabad 380054 Gujarat India

Ahmadabad
GUJARAT
380054
India 
Phone  07966213463  
Fax  07966219549  
Email  djpatel@cliantha.in  
 
Details of Contact Person
Scientific Query
 
Name  Dr Dhruv Patel 
Designation  Medical Monitor 
Affiliation  Cliantha Research Limited 
Address  Garden View Corporate House No. 8 Opp. AUDA Garden, Bodakdev, Ahmedabad 380054 Gujarat India

Ahmadabad
GUJARAT
380054
India 
Phone  07966213463  
Fax  07966219549  
Email  djpatel@cliantha.in  
 
Details of Contact Person
Public Query
 
Name  Mr Prasann Bavania 
Designation  Project Manager 
Affiliation  Cliantha Research Limited 
Address  Garden View Corporate House No. 8 Opp. AUDA Garden, Bodakdev, Ahmedabad 380054 Gujarat India

Ahmadabad
GUJARAT
380054
India 
Phone  07966219577  
Fax  07966219549  
Email  bprasann@cliantha.in  
 
Source of Monetary or Material Support  
Mylan Laboratories Limited, Bangalore 
 
Primary Sponsor  
Name  Mylan Laboratories Limited 
Address  Mylan Laboratories Limited, Bilekahalli, Bannerghatta Road, Bangalore 560076, India. Tel. No.: 080 66728000 Fax No.: 080 667828899  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL   
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 15  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Timir Shah  Divyam Hospital  Department of Psychiatry, Clinical research Room-2nd Floor, Block No. 84, Palsana Cross Road, N. H. No. 8, Palsana, Surat - 394315
Surat
GUJARAT 
9825137443

drtcshah@gmail.com 
Dr Vipul Singh  GSVM Medical College  Department of Psychiatry, Ward No.05 male surgery (Clinical research Room), Swaroop Nagar Kanpur –208005, UP, India
Kanpur Nagar
UTTAR PRADESH 
7052515253

drvipulsingh.research@gmail.com 
Dr T S Sathyanarayana Rao  JSS Medical College Hospital  Department of Psychiatry, Room no:1111, First floor, B-wing, M G Road, Mysore - 570005
Mysore
KARNATAKA 
9845282399

tssrao19@yahoo.com 
Dr Rajendra Anand  Kanoria Hospital & Research Centre  Room No. 301 (Clinical Research Room), Airport - Gandhinagar Highway, Village - Bhat, Gandhinagar - 382428
Gandhinagar
GUJARAT 
9824017400

drrajendranand@yahoo.com 
Dr Nitin Dalaya  Lifepoint multispecialty Hospital  Department of clinical research, 3rd floor, 145/1, Mumbai Bangalore Highway, near hotel Sayaji, waked Pune-411057, Maharashtra, India
Pune
MAHARASHTRA 
9552503201

Lp.feasibility@gmail.com 
Dr Ratnakar Inamdar  Medipoint Hospital Pvt. Ltd  Clinical Research Department, 3rd Floor, 241/1, New D P Road, Aundh Baner Boundry, Baner Road, Pune – 411007, Maharastra, India
Pune
MAHARASHTRA 
9372336885

drrinamdar@yahoo.com 
Dr Mahesh Chudgar  MITR Foundation  Department of Psychiatry,1st Floor, 1, Shanti Nagar Society, Way to CCD Gully, Usmanpura, Ashram Road, Ahmedabad - 380013
Ahmadabad
GUJARAT 
9825412109

mahesh_mitr@yahoo.co.in 
Dr Amar Shinde  Noble Hospitals Pvt. Ltd  Noble NX Building – Ground Floor (Clinical research department), Room No: 153, Magarpatta City Road, Hadapsar, Pune - 411013
Pune
MAHARASHTRA 
9371425020

dramarshinde2000@gmail.com 
Dr Radhika Reddy  Old Govt. General Hospital  (Associated with Govt. Siddhartha Medical College), Department of Psychiatry, Hanumanpet, Two Town, Vijayawada- 520002
Krishna
ANDHRA PRADESH 
9848229798

rrvemireddy@yahoo.com 
Dr K S Kulkarni  Oyster & Pearl Hospitals  Department of Psychiatry, Room No:504,5th Floor, 1671-75, Shivajinagar, Pune- 411005, Maharastra, India
Pune
MAHARASHTRA 
9552874787

startupfeasibility@gmail.com 
Dr Nehal Shah  Panchshil Hospital  Department of Psychiatry, 2nd Floor, New Sabarmati Railway Station, Ahmedabad - 380005
Ahmadabad
GUJARAT 
9925049569

doctornehal@gmail.com 
Dr Vaishal Vora  Ratandeep Multispecialty Hospital  Department of Psychiatry, 5th Floor, Nakshtra Complex, Above HDFC Bank, Maninagar Cross Road, Maninagar, Ahmedabad - 380008
Ahmadabad
GUJARAT 
9825440891

vnvora@gmail.com 
Dr Ramashanker Yadav  Shivam Hospital  Department of Psychiatry, C-4/ Satyanarayan Society, Gor’s Kuva Jashodanagar Char Rasta, Maninagar (E), Ahmedabad -3800578, Gujarat, India
Ahmadabad
GUJARAT 
8264049261

yadavramashanker@gmail.com 
Dr Bakul Buch  Shri Hatkesh Healthcare Foundation  Department of Psychiatry, 2nd floor, Saraswati Mandir Complex, Near Bhutnath Temple, College Road, Junagadh-362001, Gujarat, India
Junagadh
GUJARAT 
9825220330

bakulbuch@gmail.com 
Dr Ramanathan Sathianathan  Sri Ramchandra Medical college and & Research Institute  Department of Psychiatry,Basement, Central research Facility, Clinical trial division, Dental Block- Basement, No. 1, Ramchandra Nagar, Porur, Chennai - 600116
Chennai
TAMIL NADU 
9841019910

sathianathen6@yahoo.com 
 
Details of Ethics Committee  
No of Ethics Committees= 15  
Name of Committee  Approval Status 
Ethics Committee MITR Foundation  Approved 
Ethics Committee, GSVM Medical College  Approved 
Ethics Committee, Hatkesh Healthcare Foundation  Approved 
Ethics Committee, Ratandeep Multispecialty Hospital  Approved 
Institutional Ethics Committee, Divyam Hospital  Approved 
Institutional Ethics Committee, JSS Medical College & Hospital  Approved 
Institutional Ethics Committee, Noble Hospital  Approved 
Institutional Ethics Committee, Siddhartha Medical College & Govt. General Hospital   Approved 
Institutional Ethics Committee, Sri Ramchandra Medical College and Research Institute  Approved 
Kanoria Ethics Committee, Kanoria Hospital & Research Centre  Approved 
LPR Ethics Committee, Lifepoint Multispecialty Hospital   Approved 
O & P Institutional Ethics Committee, Oyster & Pearl Hospitals  Approved 
Panchshil Institutional Ethics Committee, Panchshil Hospital  Approved 
Penta-Med Ethics Committee, C/O Medipoint Hospitals   Approved 
Shivam Ethics Committee, Shivam Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Schizophrenia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  INVEGA SUSTENNA® (Paliperidone Palmitate) Extended-Release Injectable Suspension Janssen Pharmaceuticals, Inc. Titusville, NJ 08560  Dose:156 mg Route of Administration: IM 28 Days Cycle 
Intervention  Paliperidone Palmitate Extended-Release Injectable Suspension Mylan Laboratories Limited, India  Dose:156 mg Route of Administration: IM 28 Days Cycle  
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  Subjects who qualify for the study should meet the following inclusion criteria:
1.Men or non-pregnant, non-lactating females aged 18-65 years (inclusive) having clinical diagnosis of schizophrenia.
2.Subjects with Body Mass Index (BMI) less than or equal to 35 but greater than or equal to 18.
3.Subjects who are clinically stable and no hospitalization for exacerbation of psychiatric symptoms during 3 months before screening and randomization.
4.Subjects with adequate renal function defined as creatinine clearance (Cockcroft-Gault Equation,) more than or equal to 80 mL/min.
5.Adequate hematological parameters at screening and randomization defined by:
•Total white blood cell count more than or equal to 4000/mm3
•ANC more than or equal to 1500/mm3
•Platelet count more than or equal to 100,000/mm3
•Hemoglobin more than or equal to 9.0 gm/dl
6.Adequate hepatic function at screening and randomization as defined by:
•Bilirubin less than 1.5 X ULN
•AST & ALT less than 5 X ULN
7.Agree to comply with the visit schedule and other requirements of the study.

 
 
ExclusionCriteria 
Details  Subjects must not be enrolled in the study if they meet any one of the following criteria:
1.History of known hypersensitivity to paliperidone, risperidone, or to any excipients in study medications.
2.Subjects with dementia related psychosis.
3.Subjects with a history of Neuroleptic Malignant Syndrome (NMS) while on treatment with atypical antipsychotics.
4.History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval
5.Subjects with known cardiovascular disease (e.g., heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the subject to hypotension (e.g., dehydration, hypovolemia, and treatment with antihypertensive medications).
6.Subjects with clinically significant hyperprolactinemia or with possible prolactin dependent tumor.
7.History of severe hepatic impairment and drug induced leukopenia/ neutropenia/ agranulocytosis.
8.Subjects with Clinical Global Impression - Severity of illness (CGI-S) score of 5 or more.
9.Subjects with history or presence of tardive dyskinesia, seizures or other conditions that potentially lower the seizure threshold, idiopathic Parkinson’s disease, cognitive and motor impairment.
10.Subjects who are on active treatment with drugs that are known to interact with paliperidone.
11.Have a history of alcohol or drug-dependence as per DSM-V criteria during the 6-month period immediately prior to screening.
12.Subjects with clinically significant laboratory investigations as per the investigator’s judgment.
13.Attempted suicide within 12 months before screening or are at imminent risk of suicide or violent behaviour as clinically assessed by the investigator.
14.Treatment with any of the following therapies:
•Injection of risperidone long acting injection within 6 weeks before screening.
•Electroconvulsive therapy within 3months prior to screening.
•Clozapine within 3 months before screening.
•Nonselective or irreversible monoamine oxidase inhibitor (MAOI) antidepressants within 30 days before screening.
•Other antidepressant agents, unless subject had been on a stable dose for at least 3 months before screening and plans on remaining on that same exact regimen for the entire duration of the study.
•Mood stabilizers, including lithium and all anticonvulsants, beta-blockers, and anti-parkinsonian medication. Unless subjects on a stable dose for at least 3 months before screening and expect to remain on that same exact regimen throughout the duration of the study.
15.Subjects who are:
•Pregnant
•Breast feeding
•Male or female of childbearing potential unwilling to use adequate methods of contraception throughout the study.
•Subjects whom had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery, or whom have surgery scheduled during the course of the study.
•Subjects with known positivity for human immunodeficiency virus (HIV), HBsAg or HCV.
16.Participation in any interventional clinical study within the past 90 days of randomization.
17.History of difficulty with donating blood or difficulty in accessibility of veins.
18.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
19.Any reason which, in the opinion of the Principal Investigator or Co-Investigator, would prevent the subject from safely participating in the study
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To evaluate the bioequivalence of Mylan’s Paliperidone Palmitate extended-Release Injectable Suspension with Janssen’s INVEGA SUSTENNA® in subjects with schizophrenia.  After 24 Week ( post dose 6 total 19 PK sample assessment ) 
 
Secondary Outcome  
Outcome  TimePoints 
To evaluate the safety and tolerability of Paliperidone Palmitate Extended-Release Injectable Suspension of Mylan Laboratories Limited, India in subjects with schizophrenia.  To evaluate the safety and tolerability of Paliperidone Palmitate Extended-Release Injectable Suspension of Mylan Laboratories Limited, India in subjects with schizophrenia. 
 
Target Sample Size   Total Sample Size="264"
Sample Size from India="264" 
Final Enrollment numbers achieved (Total)= "267"
Final Enrollment numbers achieved (India)="267" 
Phase of Trial   Phase 1 
Date of First Enrollment (India)   14/05/2018 
Date of Study Completion (India) 10/01/2019 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="4"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Not Applicable 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

The study is Randomized, Multicenter, Multiple-dose, Two-treatment, Single-period, Parallel, Steady State Bioequivalence Study of Paliperidone Palmitate Extended-Release Injectable Suspension in Subjects with Schizophrenia under Fasting Condition.

 

This study will be initiated only after obtaining the approvals of Institutional Ethics Committee (IEC) and clinical trial permission from the Drug Controller General of India (DCGI). The subjects qualifying inclusion and exclusion criteria will be invited to participate in this study.

 

The recruitment will happen as per randomization schedule. Subject will be randomized in a 1:1 ratio to Test or Reference product.

 

Subject will receive either Mylan’s paliperidone palmitate extended-Release Injectable suspension or Janssen’s INVEGA SUSTENNA® as per the randomization. Main conclusion on the bioequivalence will be drawn based on the PK data obtained during last dosing interval. 

Plasma concentrations of Paliperidone will be measured by using a validated method.

 

Statistical analysis of pharmacokinetic parameters comparing test and reference products will be performed to assess bioequivalence. 
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