CTRI/2019/01/016865 [Registered on: 03/01/2019] Trial Registered Prospectively
Last Modified On:
30/11/2019
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A study of Paliperidone Palmitate injection in patients of abnormal behavior
Scientific Title of Study
A randomized, open label, multicenter, parallel group, multiple dose, steady state study to compare the bioavailability and characterize the pharmacokinetic profile of the sponsor’s test formulation [Paliperidone Palmitate extended release injectable suspension, (156 mg/ml)] relative to that of the reference formulation [Invega® Sustenna® (Paliperidone Palmitate extended release injectable suspension, 156 mg/ml), Janssen Pharmaceuticals, Inc., Titusville, New Jersey] and establish bioequivalence in patients of Schizophrenia already receiving a stable regimen of paliperidone palmitate extended release injectable suspension.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Prashant Modi
Designation
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 Ravi Alamchandani
Designation
Senior 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
07940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.com
Details of Contact Person Public Query
Name
Mr Prashant Modi
Designation
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.09199417878, Fax No.09199417885
Primary Sponsor
Name
Accord Healthcare Inc
Address
1009 Slater Road, Suite 210, Durham, North Carolina 27703. Tel. No.09199417878, Fax No.09199417885
Department Of clinical research,Room No 11, Subburaman Street, Gandhi Nagar-625020 Madurai TAMIL NADU
09443772233
vikhram@ahanahospitals.in
Dr Rajendra Anand
Anand Mutispeciality Hospital & Research Centre,
Department Of clinical research,Room No. NA,4th Floor, Sarthak Mall, Mahatma Mandir Road, Sargasan Cross Road-382421 Gandhinagar GUJARAT
09824017400
drrajendraanand@yahoo.com
Dr G Prasad Rao
Asha Hospital
Road No.14, Department Of clinical research,Room No. NA Banjara Hills-500034 Hyderabad TELANGANA
9985900005
prasad40@gmail.com
Dr Ashish P Contractor
Bodyline Hospitals
Department Of clinical research,Room No. NA,Opp. Annapuma Hall, Near Dev Status, New Vikas Gruh Road, Paldi-380007 Ahmadabad GUJARAT
09824012867
drashishcontractor.cr@gmail.com
Dr Timir Shah
Divyam Hospital
Divyam Institute of Psychiatry,Department Of clinical research
Block No. 84, Palsana Cross Roads, N.H. No-8-394315, Surat GUJARAT
09825137443
drtcshah@gmail.com
Dr T S Sathyanarayana Rao
JSS Medical College & Hospital
Department Of clinical research,Room No.1111, First Floor, B Wing, Department of Psychiatry, JSS Medical College & Hospital,
MG Road-570004 Mysore KARNATAKA
09845282399
tssrao19@yahoo.com
Dr Nitin Dalaya
Lifepoint Multispecialty Hospital
Sr. No. 145/1, Mumbai - Bangalore Highway , Near Hotel Sayaji, Department Of clinical research,Room No. NA, Bhumkar Chowk, Wakad-411057 Pune MAHARASHTRA
9552503201
drdalaya@nityanandrehab.com
Dr K S Kulkarni
Oyster and Pearl Hospital
1671-75,Ganeshkhind Road, Department Of clinical research, Room No. NA, Shivaji Nagar-411005 Pune MAHARASHTRA
9822116995
omksk54@gmail.com
Dr Vaishal Vora
Ratandeep Multi Speciality Hospital
Department Of clinical research,Room No. NA,5th Floor, Nakshatra Complex, Above HDFC Bank, Maninagar Cross Road, Maninagar-380008 Ahmadabad GUJARAT
09825440891
vnvora@gmail.com
Dr Bakul Buch
Shri Hatkesh Healthcare Foundation
Department Of clinical research,Room No. NA,Sarasawti Mandir Complex,
Near Bhutnath Temple, College Road-362001 Junagadh GUJARAT
09825220330
bakulbuch@gmail.com
Dr R Sathianathan
Sri Ramachadra Hospital
Department Of clinical research,Room No.1, Ramachandra Nagar, Porur-600116 Chennai TAMIL NADU
Dose: 156 mg,; Frequency:
once per month; Mode of
Administration: Intra muscular; Duration of treatment: 6 doses (one per every 28 days)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Written informed consent for participation in the study by the patient and patient’s legal acceptable representative (LAR).
2. Schizophrenic male or female patients, between 18 and 75 years of age (both inclusive)
3. Patients having BMI between 18-35 kg per meter square (up to 2 percentage deviation is acceptable) and at least 50 kg weight for male patients and 48 kg for female patients.
4. Patients who are stabilized on 156 mg dose of paliperidone palmitate extended release injectable suspension once every month (atleast 3 doses prior to randomization) would be eligible to participate in the study by continuing their established maintenance dose.
5. Patients have a documented clinical diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition
6. Patients having Clinical Global Impression scale score of less than or equal to 4 at both screening and Baseline.
7. Patients not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening, medical history, physical examination, 12-lead ECG recordings and Chest X-ray.
8. Adequate hematological parameters at screening and randomization
9. Adequate hepatic function at screening and randomization
10. Patients able to comply with study procedures in the opinion of the investigator.
11. In case of Male patients: Either partner or patient must use an effective method of avoiding pregnancy for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
12. Sexually active women, unless surgically sterile (at least 6 months prior to study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician
ExclusionCriteria
Details
1. Patients with current or relevant history of psychiatric illness except schizophrenia.
2. Patients with clinically significant illnesses or major surgery within 4 weeks prior to the screening.
3. Patients with DSM-V diagnosis of substance-related disorders within 180 days before the date of screening.
4. Patients with concurrent condition of Parkinson disease (except for drug-induced extrapyramidal syndrome). Patients with history or presence of tardive dyskinesia. Patients with cognitive and motor impairment.
5. Patients with concomitant treatment with hepatic enzyme inhibitors (including fluoxetine or paroxetine) or medications known to interact with study medication within 2 weeks of the first injection of study medication.
6. Administration of thioridazine, or ziprasidone within 2 weeks of the first study-related procedure; receiving tablet paliperidone within 2 months of the first study-related procedure.
7. Presence of syncope or orthostatic hypotension (defined as systolic blood pressure decrease of at least 30 mmHg or a diastolic blood pressure decrease of at least 20 mmHg within one to three minutes of standing up).
8. Patients with uncontrolled hypertension
9. Patients with known cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration, hypovolemia or any medications).
10. Patients with inadequate mass in the deltoid or gluteal regions to receive the intramuscular drug injection.
11. Patients with any condition which in the opinion of the investigator makes the patient unsuitable for inclusion.
12. Patients with creatinine clearance (using Cockcroft Equation) less than 80 mL per min
13. Patients with severe hepatic impairment based on the Child-Pugh classification
14. Patients with diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months prior to screening, or diagnosis of substance abuse within 3 months prior to screening.
15. Donation of blood (greater than or equal to 1 unit or 350 mL) within 90 days prior to receiving the first dose of study medication or during the study.
16. Patient attempted suicide within 12 months before screening or current thoughts of suicide (suicidal ideation) or violent tendencies/ behavior.
17. Patients with positive result for any of the serology tests (Hepatitis B, C and HIV)
18. Patient with known hypersensitivity/ intolerance to study drug or any other component of the drug.
19. A history of granulocytopenia, agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic).
20. Positive tests for drug or alcohol abuse at screening and/or baseline.
21. Receipt of an investigational medicinal product or participation in a drug research study within 90 days prior to receiving the first dose of study medication or during the study.
22. Psychosis judged to be the direct physiological effect of an abused medication or substance.
23. Hospitalisation for an exacerbation of schizophrenia within two months prior to screening and during the screening period.
24. Patients with the following cardiac conditions are excluded:
a. Recent myocardial infarction (less than 12 months)
b.QTc prolongation (screening electrocardiogram with QTc greater than 450 msec for men, QTc greater than 470 msec for women as calculated using Bazett’s Formula)
c. History of QTc prolongation or using concomitant medications which prolong QTc interval.
d.First-degree heart block with PR interval greater than 0.22 seconds.
e. Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia
f. Uncompensated congestive heart failure, myocarditis, cardiomyopathy
g.Complete left bundle branch block.
25. Patients with uncontrolled Diabetes mellitus
26. A history of epilepsy or multiple syncopal episodes. Patients with seizures or other conditions that potentially lower the seizure threshold.
27. Patient with hyperprolactinemia at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
28. Dementia related psychosis.
29. Concurrent use of other drugs known to suppress bone marrow function.
30. Pregnant or lactating females.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Comparision of the bioavailability and characterization of the pharmacokinetic profile of the Sponsor’s formulation with that of reference formulation and establish bioequivalence
Day 85, Day 113, Day 141, Day 142, Day 143, Day 144, Day 145, Day 146, Day 147, Day 148, Day 149, Day 150, Day 152, Day 154, Day 156, Day 158, Day 161, Day 165, Day 169
Secondary Outcome
Outcome
TimePoints
Safety of the patients who are exposed to the investigational medicinal product
Throughout the study
Target Sample Size
Total Sample Size="240" Sample Size from India="240" 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)
15/02/2019
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="1" Months="8" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
None Yet
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
It is an open label, multicenter, parallel group, multiple dose, steady state study. Paliperidone is a benzisoxazole derivative with potent antipsychotic properties, is indicated for the treatment of schizophrenia. The Sponsor has developed Paliperidone Palmitate extended release injectable suspension. This formulation being extended release formulation, it is expected to improve the compliance, which is very important considering schizophrenic population. This study is being conducted to characterize the pharmacokinetic profile and prove bioequivalence of the Sponsor’s formulation with respect to the reference formulation in Schizophrenic patients stabilized on Paliperidone Palmitate extended release injectable suspension, (156 mg/ml per month). As a high number of healthy subjects experienced serious adverse effects after administration of antipsychotics such as hypotension, tachycardia etc., hence, regulatory authorities are recommending that studies should be conducted on Schizophrenic patients. At the screening visit (within -2 weeks before the first dose visit), after giving informed consent, potential study participants will undergo screening examinations to assess eligibility for inclusion in the trial. The objective of the present study is to assess and compare the bioavailability and to characterize the pharmacokinetic profile of the Sponsor’s formulation (with respect to the reference formulation in schizophrenic patients and establish bioequivalence. Through this study, we will prospectively collect the data from adult schizophrenic patients who will be randomly assigned to receive either test product or reference product for the pharmacokinetic profiling.