CTRI/2021/06/033960 [Registered on: 02/06/2021] Trial Registered Prospectively
Last Modified On:
13/10/2022
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Pharmacokinetic study of Paliperidone Extended Release Injectable Suspension 156 mg in patients with schizophrenia and/ or schizoaffective disorder.
Scientific Title of Study
A multicenter, open label, randomized, balanced, two-treatment, two-period, two-sequence, multiple dose, steady state crossover bioequivalence study of Paliperidone Palmitate Extended Release Injectable Suspension 156 mg of Sun Pharmaceutical Industries Limited, India. with that of Invega Sustenna® (Paliperidone Palmitate) Extended Release Injectable Suspension 156 mg of Janssen Pharmaceuticals, Inc. in patients with schizophrenia and/ or schizoaffective disorder
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2020/014, Version No. 1.0 Protocol Date 15-JUL-2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Kanchan Tyagi
Designation
Senior Manager
Affiliation
Sun Pharmaceuticals Industries Limited
Address
Plot No. GP-5, Sector 18, HSIDC
Gurgaon 122015, Haryana, India Gurgaon HARYANA 122015 India
Clinical Research Department
4th And 5th Floor,
Star Plus Complex, MG Road,
Near Muktidham Mandir Nashik MAHARASHTRA
9819625217 02532461324 nakulv1986@gmail.com
Dr Minakshi Parikh
B.J. Medical College and Civil Hospital
Asarva, Ahmedabad – 380016, Gujarat, India Ahmadabad GUJARAT
9825718698
drminakshiparikh@gmail.com
Dr Manish Thakre
Government Medical College and Hospital
Department of Psychiatry, Government Medical College and Hospital, Medical College Square, Near Hanuman Nagar, Nagpur-440003, Maharashtra, India Nagpur MAHARASHTRA
9850977266
drmanishthakre@gmail.com
Dr Shah Tarak Parmanandbha
MITR Foundation
1, Shantinagar Society, Way to CCD Gully, B/h Hotel Holiday Inn Express, Usmanpura, Ashram Road, Ahmedabad-380013, Gujarat, India Ahmadabad GUJARAT
9824096430 079-27552623 tarak_mitr@yahoo.co.in
Dr Vinod Kumar Goyal
Parth Hospital
2nd Floor, Near Basudiwala School, Nadiad-384001, Gujarat, India Kheda GUJARAT
9824048232
drvgo999@gmail.com
Dr Vaishal Vora
Ratandeep Multispeciality Hospital
Nakshatra Complex Above HDFC Bank, Maninagar Cross Rd, Maninagar, Ahmedabad, Gujarat-380008, India Ahmadabad GUJARAT
Anand Ethics Committee, Anand Multispecialty Hospital and Research Centre Sarthak mall Mahatma Mandir Road Sargasan Cross Road Gandhinagar Gujarat
Approved
INSTITUTIONAL ETHICS COMMITTEE, B.J. MEDICAL COLLEGE AND CIVIL HOSPITAL, OFFICE OF MEDICAL SUPERINTENDENT CIVIL HOSPITAL, Ahmedabad, Gujarat - 380016, India
Approved
Institutional Ethics Committee,GMC,Nagpur Government Medical College and Hospital, Government Medical College, Medical Square Hanuman Nagar, Nagpur, Maharashtra - 440003 India
Sujata Birla Hospital Ethics Committee, Sujata Birla Hospital and Medical Research Center, Opposite Bytco college, Nashik Pune Highway, Nashik Maharashtra - 422101 India
Paliperidone Palmitate Extended Release Injectable Suspension 156 mg of Sun Pharmaceutical Industries Limited, India.
Paliperidone Palmitate Extended Release Injectable Suspension 156 mg (1.0 mL) will be administered at predefined injection site from prefilled syringe by intramuscular route, monthly.
Duration of therapy: 5 monthly doses
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Patients willing and able to provide voluntary written informed consent and to follow the protocol requirements.
2. Male or Female patients with negative serum pregnancy test at screening, between 18 and 65 years of age, both inclusive, and having Body mass index equal or more than 18.00 calculated as weight in kg/height in m2 and at least 50 kg weight for male patients and 48 kg for female patients.
3. Patients who meets diagnostic criteria for schizophrenia and/ or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V).
4. Patients who are clinically stable and not hospitalized for exacerbation of psychiatric symptoms during 3 months before screening and till randomization.
5. Patients receiving Paliperidone long-acting injection at a dose of 156 mg/mL via the intramuscular route and have completed at least two maintenance doses prior to randomization.
Note: Patients who will enter in to the lead-in period: The criteria will be evaluated during screening part-II.
6. Acceptable hematology status:
a. Hemoglobin ≥ 9.0 g/dL
b. Absolute neutrophil count (ANC) ≥ 1500 cells/µL
c. Platelet count ≥ 1,00,000 cells/µL
7. Acceptable liver function:
a. Alanine aminotransferase (ALT) ≤ 2.0 X upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) ≤ 2.0 X ULN
c. Total bilirubin < 1.2 mg/dL
d. Alkaline phosphatase ≤ 2.0 X ULN
8. Patients with creatinine clearance ≥ 80 mL/minute (using the Cockcroft-Gault Equation).
9. Females of childbearing potential must be willing to use adequate contraception (as defined below) from the first study dose and agree to follow throughout the study and for at least 6 months after the last dose of the investigational product. For this study, acceptable and effective methods of contraception for females include:
a. Intrauterine device placed at least 6 months prior to the first study dose and agree to follow throughout the study,
b. Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide plus a male or female condom) or
c. Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner)
OR
Females who are surgically sterile
OR
Females who are post-menopausal for at least one year
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 6 months following the last dose of the study.
a. Absolute sexual abstinence (no sexual intercourse or genital contact with a female partner).
b. Use of barrier method with spermicide
No history of addiction to any recreational drug or drug dependence or alcohol addiction.
ExclusionCriteria
Details
1. Known hypersensitivity to paliperidone Palmitate or risperidone or to any of the excipients of investigational product or to any other similar class of drugs.
2. Patients having current thoughts of suicide (suicidal ideation) or violent tendencies at the time of screening as per investigators discretion.
3. Patients with history or presence of neuroleptic malignant syndrome or tardive dyskinesia, dementia related psychosis, Parkinsons disease or epilepsy or seizures or cognitive and motor impairment.
4. Patients with history of arrhythmia.
5. Patients with positive urine screen for drugs of abuse (except for benzodiazepine which is a permissible medication supported by written prescription).
6. Patient with positive alcohol breath test.
7. History or current signs and symptoms of severe, progressive, or uncontrolled pulmonary, cardiac, gastrointestinal, hepatic, renal, genitourinary, hematological, endocrine, immunologic, metabolic or neurological disease.
8. Corrected QT interval [Bazetts formula] more than 450 msec (male) or more than 470 msec (female) at screening or prior to administration of the first dose of IP, or with a known history of Torsades de Points, or family member with sudden unexplained cardiac death.
9. History of cardiac disease which predispose to QT prolongation (sick sinus, complete AV block, CHF, ventricular tachycardia, hypokalemia or hypocalcaemia) or current medication of QT prolonging drugs.
10. Significant orthostatic hypotension (i.e. a drop in systolic blood pressure of 20 mm Hg or more and or a drop in diastolic blood pressure of 10 mm Hg or more within 3 minutes of standing) or history of syncope at screening.
11. Current or anticipated use of any of the prohibited medications during study participation.
12. Patient with skin abnormalities or irritations at the potential injection site (right or left deltoid or gluteal) as determined by the investigator.
13. Smokers who smokes greater than or equal to 10 cigarettes or equivalent per day.
14. Any clinically significant abnormal laboratory parameter or clinically significant organ abnormality found evaluated during screening evaluation.
15. Patients with any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study that would limit adherence to study requirements.
16. Lactating women.
17. Current surgical or other non-healing wounds or major surgical procedure (including periodontal) within 28 days of first study dose of IP.
18. Patients with positive serology for Hepatitis B Virus, Hepatitis C Virus or Human Immunodeficiency Virus.
19. Participation in any clinical study within 90 days before the first dose of Investigational Product.
20. Loss of more than equal to 350 mL of blood within 90 days before the first dose of Investigational Product.
21. Patients with suspected (signs and symptoms of COVID19) or confirmed novel coronavirus infection or with history of travel or contact with any COVID19 positive patient or isolation or quarantine.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
Primary Parameters: Peak concentrations during the dosing interval at steady-state, Area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state
Secondary Parameters: Minimum or trough concentrations at steady-state, Time of the maximum measured plasma concentration at steady state, Degree of fluctuation (percentage), Average plasma concentration at steady state, Swing
At the end of the study when all 80 patients have
completed the study
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients after investigational product administration
At the end of the study when all 80 patients have
completed the study
Target Sample Size
Total Sample Size="80" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
A comparative bioequivalence study Paliperidone Palmitate Extended Release Injectable Suspension 156 mg of Sun Pharmaceutical Industries Limited, India. with that of Invega Sustenna®(Paliperidone Palmitate) Extended Release Injectable Suspension 156 mg of Janssen Pharmaceuticals, Inc. in patients with schizophrenia and/ or schizoaffective disorder. The study will be conducted at multiple investigator sites across India. Sufficient number of patients will be screened and enrolled in order to have 80 evaluable patients. Enrolment will continue until at least 80 patients complete both study periods. There is two periods in this study. Patients shall be randomized either test or reference for consecutive five dosing i.e. on day 1, day 29, day 57, day 85, day 113 (Period 01). Patients will then be switched over to the other treatment (period 02) based on randomization schedule for the next consecutive five doses i.e. on day 141, day 169, day 197, day 225 and day 253. Patient shall continue to receive the injection in the same anatomical location i.e. deltoid or gluteal muscle as per randomization for the entire duration of the study. Deltoid injections should be alternated between the two deltoid muscles†and “Gluteal injections should be alternated between the two gluteal muscles. Alternate muscle is recommended to avoid any haematoma or other injection site adverse events.