CTRI/2021/06/034105 [Registered on: 09/06/2021] Trial Registered Prospectively
Last Modified On:
25/04/2024
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A Bioequivalence in Patients with Schizophrenia already receiving a stable Regimen of Paliperidone Palmitate Extended Release Injectable Suspension.
Scientific Title of Study
A Randomized, Open Label, Two Stage, Multicentre, Parallel Group, Multiple Dose, Steady State Study to Compare Bioavailability and Characterize Pharmacokinetic Profile of Test Formulation
[Paliperidone Palmitate Extended Release Injectable Suspension By Accord Healthcare,Administered Every Three Months] Relative to Reference Formulation [Invega Trinza®(Paliperidone Palmitate Extended Release Injectable Suspension) By Janssen Pharmaceuticals]
and to Establish Bioequivalence in Patients with Schizophrenia Already Receiving A Stable Regimen of Paliperidone Palmitate Extended Release Injectable Suspension.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0419-20,Version: 1.0,Date: 29 January 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Prashant Modi
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of CTM Medical Services, Plot No.
38,Survey No. 388 Near Silver Oak Club, S. G. Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202389
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Prashant Modi
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Accord Healthcare Inc,1009 Slater Road, Suite 210, Durham,North Carolina
27703,Tel.No.:9199417878
Primary Sponsor
Name
Accord Healthcare Inc
Address
1009 Slater Road, Suite 210, Durham, North Carolina 27703
Tel.No.:9199417878
Department of Clinical Research,Room No. #35A, Clinical Research Centre, Adichunchanagiri Hospital & Research Centre, B.G. Nagara, Nagamangala, Mandya, Karnataka-571 448. Mandya KARNATAKA
9980038331
drvinayhr@bgsaims.edu.in
Dr Vikhram Ramasubramanian
Ahana Hospitals LLP
Department of Clinical Research,Room No. 07, Subburaman Street, Gandhi Nagar- 625020 Madurai TAMIL NADU
9443772233
vikram@ahanahospitals.in
DrRajendra Anand
Anand Multispeciality Hospital & Research Centre
Department of Clinical Research,Room No.N/A, Anand Multispeciality Hospital & Research Centre, 4th floor, sarthak mall, Mahatma mandir road, sargasan cross road,Gandhinagar Gandhinagar GUJARAT
9824017400
drrajendraanand@yahoo.com
DrRajendra Someshwar Anand
Anand Multispeciality Hospital & Research Centre
Department of Clinical
Research,Room No.N/A,Anand
Multispeciality Hospital
& Research Centre, 4th floor, sarthak mall,
Mahatma mandir road,sargasan cross road,Gandhinagar.
Gandhinagar GUJARAT
9824017400
drrajendraanand@yahoo.com
Dr K S Ramakrishnan
Athma Hospital And research Pvt Ltd
Department of Clinical Research,Room No. 12 B, C 10th Cross (east) Thillai Nagar, tamil Nadu, 620018 Tiruchirappalli TAMIL NADU
9538800755
athmacrc@gmail.com
Dr P N Suresh Kumar
Chethana Centre for Neuropsychiatric Rehabilitation
Department of Clinical Research,Room No.N/A, Providence College Road, Malaparamba, Kerala Kozhikode KERALA
9447218825
drpnsuresh@gmail.com
Dr Malay
Divine Multispeciality Hospital
Department of Clinical Research, Room No. 2nd & 3rd floor, Shikshapatri sky court, Near swagat flamingo, sargasan, Gandhinagar- 382421 Gandhinagar GUJARAT
9428916387
drmalaypatel.research@gmail.com
DrTimir Shah
Divyam Hospital
Department of Clinical Research, Room No. 84, Divyam Hospital, Palsana cross road, N.H. No.8, Surat, Palsana-394315 Surat GUJARAT
9825137443
drtcshah@gmail.com
DrTimirkumar shah
Divyam Hospital, Palsana, Surat
Department of Clinical
Research,Room No.N/A,Divyam Hospital, Block no.84,Palsana cross road, N.H. No.8, Surat, Palsana-394315 Surat GUJARAT
9825137443
divyamhospital@gmail.com
Dr Dhananjay Chaudhari
G S V M Medical College Kanpur
Department of Clinical Research, Room No. N/A, Department of Psychratric, LLR Hospital GSVM medical collage Swaroop nagar, kanpur, 208002, UP, India Kanpur Nagar UTTAR PRADESH
9336049009
georgiandc@gmail.com
Dr Satyanarayana Rao TS
JSS Medical College and Hospital
Department of Clinical Research,Room No.N/A, department of Psychiatry, JSS Medical College Hospital , No.1111, First Floor, B Wing, M G Road, Mysore - 570 004,Karnataka. Mysore KARNATAKA
9845282399
tssrao19@yahoo.com
Dr TS Sathyanarayana Rao
JSS Medical College Hospital
JSS Medical College Hospital , Department of Clinical Research, Room No.1111, First Floor, B Wing, Psychiatry department, M G Road, Mysore 570 004,Karnataka. Mysore KARNATAKA
9845282399
tssrao19@yahoo.com
Dr Nitin Dalaya
Lifepoint Multispeciality Hospital
Department of Clinical Research, Room No.145/1,Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune - 411057, Maharashtra, India. Pune MAHARASHTRA
9552503201
drndalaya@gmail.com
DrNitin Dalaya
Lifepoint Multispecialty Hospital, Pune
Department of Clinical
Research,Room No145/1,Mumbai
Bangalore Highway,Near Hotel Sayaji,Wakad, Pune - 411057 Pune MAHARASHTRA
9552503201
drndalaya@gmail.com
Dr Bhavik N Shah
Medistar Multi Speciality Hospital
Department of Clinical Research,Room No.N/A, Medistar Multi Speciality Hospital, , Trimurti Avenue, Industrial Area, Himatnagar, Sabarkantha, Gujarat - 383001 Sabar Kantha GUJARAT
9909541563
drbhavikpatelpsy@gmail.com
Dr K S Kulkarni
Oyster & Pearl Hospitals
Oyster and Pearl Hospital(Phadnis Clinic Pvt Ltd),No.1671-75, Ganeshkhind road, shivaji nagar,Pune-411005. Pune MAHARASHTRA
9657890461
startupfeasibility@gmail.com
Dr K S Kulkarni
Oyster and Pearl Hospital(Phadnis Clinic Pvt Ltd)
Department of Clinical Research, Room No. 1671-75, Ganeshkhind road, shivaji nagar-411005 Pune MAHARASHTRA
9657890461
startupfeasibility@gmail.com
Dr Vinod Kumar Goyal
PARTH Hospital
Department of Clinical Research, Room No. N/A, Parth Hospital,2nd Floor Near Basundiwala School. Paras Circule, collage Road, Nadiad 387001 Anand GUJARAT
9824048232
drvgo999@gmail.com
Dr Ramashankar Yadav
Pramukh multispeciality Hospital
Department of Clinical Research, Room No.N/A, Pramukh multispeciality Hospital, Near railway Crossing, Above iloj medical Store, Maninagar, Khokhra, Ahmedabad, 380008 Ahmadabad GUJARAT
8264049261
yadavramashanker@gmail.com
DrVaishal Vora
Ratandeep Multispeciality Hospital
Department of Clinical Research, Room No.N/A, Ratandeep Multispecialty Hospital, Nakshatra Complex, above HDFC Bank, Maninanagar Cross Road, Maninagar, Ahmedabad-380008,Gujarat, India. Ahmadabad GUJARAT
9825440891
vnvora@gmail.com
DrVaishal N Vora
Ratandeep Multispecialty Hospital
Department of Clinical
Research,Room No.N/A,Ratandeep Multispecialty Hospital,
Nakshatra Complex,above HDFC Bank,Maninanagar Cross
Road, Maninagar, Ahmedabad-380008,Gujarat,India. Ahmadabad GUJARAT
9825440891
vnvora@gmail.com
Dr Ashok Goyal
Sardarmal Khandaka Memorial Hospital
Department of Clinical Research, Room No. N/A, Sardarmal Khandaka Memorial Hospital, Bhagwan Mahaveer Psychiatry and DE-addiction Center, Next to Chirayu Hospital, Kalwar Road, Hathoj, Jaipur-302012, Rajasthan. Jaipur RAJASTHAN
9828809333
ashokgoyaldr@yahoo.com
Dr Ashok Goyal
Sardarmal Khandaka Memorial Hospital
Sardarmal Khandaka Memorial Hospital,Bhagwan Mahaveer Psychiatry and DE-addiction Center A unit of Sardarmal Khandaka Memorial Hospital, Next to Chirayu Hospital Kalwar Road, Hathoj Jaipur-302012,Rajasthan Jaipur RAJASTHAN
9828809333
ashokgoyaldr@yahoo.com
DrBakul Buch
Shri Hatkesh Healthcare Foundation
Department of Clinical
Research,Room No.N/A,Shri Hatkesh Healthcare Foundation,Saraswati mandir
complex,opp.Bhutnath Temple,
Junagadh-362001. Junagadh GUJARAT
9825220330
Bakulbuch@gmail.com
DrBakul Buch
Shri Hatkesh Healthcare Foundation
Department of Clinical Research, Room No.N/A, Shri Hatkesh Healthcare Foundation, Saraswati mandir complex, opp. Bhutnath Temple, Junagadh-362001. Junagadh GUJARAT
Dose formulation-Each 1.75 mL prefilled syringe contains 546 mg paliperidone palmitate,Dosage Level-Total 4 doses of 546 mg IM (deltoid or gluteal) injection as per randomization every 3 months,Route of Administration-Intramuscular (deltoid or gluteal)injection
Dose formulation-Each 1.75 mL prefilled syringe contains 546 mg paliperidone palmitate,Dosage Level-Total 4 doses of 546 mg IM (deltoid or gluteal) injection as per randomization every 3 months,Route of Administration-Intramuscular (deltoid or gluteal)injection,
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1.Participants and their legally acceptable representative must sign an ICF indicating that he or she understands the purpose of, and procedures required for the study as described in in this protocol and is willing to participate in the study.2.Male or female participant must be between 18 to 75 years of age (both inclusive), at the time of signing the informed consent.3.Participants having body mass index (BMI) between 18 and 30 kgm² (BMI weightandheight2), inclusive, and at least 50 kg weight for male patients and 48 kg for female patients.4.Participants who met diagnostic criteria for schizophrenia according to DSM-5 criteria as per institutional practice. If participants have been initially diagnosed with DSM IV criteria than diagnosis should be reconfirmed as per DSM-5 criteria according to standard institutional practice.5.Participants must be clinically stable, defined as no hospitalizations for acute exacerbations, no changes in any antipsychotic medication within 3 months and CGI (severity) scale more than 4 at screening and randomization.6.Participants who are medically stable on the basis of physical examination, medical history, and vital signs and 12-lead ECG performed at screening. Any abnormalities, must be consistent with the underlying illness in the study population and this determination must be recorded in the participant source documents and initialed by the investigator.7.Participants who are medically stable on the basis of clinical laboratory tests performed at screening and baseline. If the results of the serum chemistry panel are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participants source documents and initialed by the investigator.8.Participants, who are at randomization visit,stabilized on 156 mg 1.5 mL dose of paliperidone palmitate extended release (156 mg paliperidone palmitate equivalent to 100 mg paliperidone) injectable suspension once every month (at least 4 doses (apart from the 234 mg loading dose) prior to randomization) would be eligible for randomization in the study at the Investigators discretion OR Patients, who are at randomization visit,already stabilized (at least one dose) on 546 mg 1.75 mL(546 mg paliperidone palmitate equivalent to 350 mg paliperidone) of Paliperidone Long-acting injection once every 3 months would be eligible for randomization in the study at the Investigators discretion.9.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies-•Is not a woman of childbearing potential (WOCBP)OR•Is a WOCBP and using an acceptable contraceptive method as described in Appendix 10.4 for at least 4 weeks prior to start of stabilization period or prior to study drug administration (as applicable),during the intervention period or stabilization period (as applicable) and for at least 6 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the intervention period or stabilization period (as applicable) and for at least 6 months after the last dose of study intervention. Cessation of birth control after this point should be discussed with a responsible physician. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.•A WOCBP must have a negative serum pregnancy test at screening, and negative urine pregnancy test on day 1 before randomization, no more than 7 days before first dose of study intervention.•The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.10.Male participants are eligible to participate if they agree to the following during the stabilization or intervention period and for at least for at least 4 weeks prior to start of stabilization period or study drug administration and for at least 6 months after the last dose of study intervention-•Must not plan to father a child while enrolled in this study or within 6 months after the last dose of study intervention.•Must agree not to donate sperm for the purpose of reproduction PLUS either of the following:•Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR •Must agree to use contraception/barrier as detailed below a male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person.
ExclusionCriteria
Details
1.History of clinically significant liver or renal insufficiency, cardiac, vascular,pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances as per investigators discretion.
2.Known allergies, hypersensitivity, or intolerance to risperidone, Paliperidone or to any excipients in study medications as per prescreening information of Invega Trinza.
3.Contraindications to the use of risperidone or Paliperidone long acting injection as per prescreening information of Invega Trinza.
4.History of no response to risperidone or paliperidone when psychotic or acutely psychotic. Lack of response is defined as participants who have had a documented medical history of no clinical response, despite adequate doses and durations of treatment, or the inability to tolerate effective doses.
5.Participants with history or presence of neuroleptic malignant syndrome (NMS),tardive dyskinesia, dementia-related psychosis, mood disorders or seizure disorder and Parkinsons disease at Screening and randomization visit.
6.Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
7.Had major surgery, (eg, requiring general anesthesia) within 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
8.Participants with inadequate mass in the deltoid or gluteal regions to receive the intramuscular drug injection as clinically assessed by the investigator.
9.History of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
10.History of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
11.History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 6 months before Screening or positive test result(s) for alcohol or drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, and amphetamines) (except for benzodiazepines which are permissible when supported by a prescription) at screening and at randomization visit.
12.Patients with known cerebrovascular disease (e.g. stroke).
13.Patients with poorly controlled diabetes mellitus (defined as failure to achieve appropriate HbA1c goal based on clinical guidelines despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin or other patient-specific condition) at the time of screening.
14.Patients with uncontrolled hypertension (systolic BP more than 140 mmHg/diastolic BP less than 90 mmHg) at the time of screening and at randomization visit.
15.Presence of syncope or orthostatic hypotension (defined as systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least 10 mmHg within one to three minutes of standing up) at the time of screening and randomization.
16.History or presence of significant hyperprolactinemia due to causes other than antipsychotic drugs use at screening.
17.History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death in association with the use of drugs that prolong the QTc interval, including
• Heart rate more than 50 beats per minute, based on at least 2 measurements of supine pulse at screening or baseline.(Resting heart rate should be measured for a full minute.)
• Demonstration of repeated prolonged QTc interval more than 450ms, as measured on more than one ECG (either during screening, or from prior medical record). It is either machine-read or manually over-read.
• The following cardiac conditions- sick sinus syndrome, complete atrioventricular block, uncompensated congestive heart failure, polymorphic ventricular tachycardia
• Presence of clinically significant hypokalemia or hypomagnesemia
• Concomitant use of drugs that prolong the QTc interval (including Class Ia (eg, quinidine, procainamide) or Class III (eg, amiodarone, sotalol) antiarrhythmic medications)
• History of congenital prolongation of the QT interval (Romano-Ward Syndrome, Jervell and Lange-Nielsen syndrome)
18.Patient with known history or current symptoms of any of the following clinically significant cardiac conditions within the past 6 months prior to screening:
• Unstable angina or myocardial infarction
• New York Heart Association (NYHA) functional classification for cardiac disease of Class III or greater
• Serious cardiac arrhythmia
• Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
• Any other cardiac illness that could lead to a safety risk to the patient
• Cerebrovascular disease, or conditions that predispose the Participant to hypotension (e.g., dehydration, hypovolemia, and treatment with antihypertensive medications known to cause orthostatic hypotension).
19.Patients who are on active treatment with drugs that are known to interact with paliperidone (such as Strong P-gp inducers, Strong CYP2D6 and CYP3A4 inhibitors or inducers, drugs known to prolong the QT interval; detailed list is provided in Appendix 10.6).
Note:If the patient was on any of these drugs, sufficient wash out period (of at least 5 half-lives) must have elapsed since the last dose of such drug before the first dose of investigational medicinal product for the current study.
20.Attempted suicide within 12 months before screening or are at imminent risk of suicide or violent behaviour as clinically assessed by the investigator.
21.Participant who answered yes to either question 4 (active suicidal ideation with some intent to act, without specific plan) or question 5 (active suicidal ideation with specific plan and intent) on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C–SSRS) or answered yes to any of the suicide-related behaviors (actual attempt,interrupted attempt, aborted attempt, preparatory act or behavior) on the suicidal behavior portion of the C–SSRS at screening and at baseline.
22.Received an investigational intervention (except paliperidone) or used an invasive investigational medical device within 3 months or 5 half-lives prior to Baseline, whichever is longer, before the signing the consent or is currently enrolled in an investigational study.
23.Participant with difficulty with donating blood or difficulty in accessibility of veins.
24.Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterize the pharmacokinetic profile and to assess the bioequivalence of Paliperidone Palmitate extended release injectable suspension-test relative to Paliperidone Palmitate extended release injectable suspension-Reference in patients with Schizophrenia.
To characterize the pharmacokinetic profile of Paliperidone Palmitate extended release injectable suspension-test relative to Paliperidone Palmitate extended release injectable suspension-Reference in patients with Schizophrenia.
Following pharmacokinetic parameters will be evaluated for Paliperidone in plasma:
Pre dose 01 (day 1 ± 7), 02 (day 91 ± 7), 03 (day 381 ± 7) and 04 (day 271 ± 7): Cpd
Secondary PK parameters at steady state: Tmax,ss, Cav,ss, Cmin,ss, Degree of Fluctuation (%) and swing (%)
To compare the safety of Paliperidone Palmitate extended release injectable suspension-test relative to Paliperidone Palmitate extended release injectable suspension-Reference in patients with Schizophrenia
Frequency and/or incidence of significant clinical signs and symptoms, and laboratory abnormalities during treatment- up to Day 361
Target Sample Size
Total Sample Size="360" Sample Size from India="360" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
10/06/2021
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="3" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Nil
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, open label, two stage, multicenter, parallel group, multiple dose, steady state study to compare the bioavailability and characterize the pharmacokinetic profile of the test formulation [Paliperidone Palmitate extended release injectable suspension, (546 mg/1.75 mL), by Accord Healthcare Inc., USA administered every three months] relative to that of the reference formulation [Invega® Trinza® (Paliperidone Palmitate extended release injectable suspension, 546 mg/1.75 mL), by Janssen Pharmaceuticals, Inc., Titusville, New Jersey, USA] and establish bioequivalence in patients with Schizophrenia already receiving a stable regimen of paliperidone palmitate extended release injectable suspension.
A target of 360 participants will be randomly assigned in this study with 180 participants planned per intervention group.
The study will be conducted in below mentioned phases :
• A 14-day screening phase: Screening assessments will be performed within 14 days prior to the initiation of stabilization procedures OR within 14 days of the first Investigational Medicinal Product (IMP) administration on Day 1 of treatment period.
• Stabilization Phase of maximum up to 4 months (as applicable)
• Treatment phase of total 4 dose of 3 monthly injection of test or reference product. Extensive blood samples (covers a complete dosing interval) will be taken for PK characterization after 4th dose."