CTRI/2022/02/040103 [Registered on: 08/02/2022] Trial Registered Prospectively
Last Modified On:
04/08/2022
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Two-treatment Bioequivalence Study of Paliperidone Palmitate in adult schizophrenic patients
Scientific Title of Study
A Randomized, Open Label, Multicenter, Two-treatment, Single-period, Multiple Dose, Parallel, Steady State Bioequivalence Study of Paliperidone Palmitate (3-month) Extended Release Injectable Suspension for intramuscular use 546 mg (350 mg Paliperidone) (Pharmathen S.A., Greece) compared to TREVICTA® 350 mg Prolonged Release Suspension for injection (Janssen-Cilag International NV, Belgium) in adult schizophrenic patients.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
21-VIN-0412 version 01 dated 25 Oct 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sumit Arora
Designation
Vice President Clinical Operations
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi Ahmedabad – 380 015, India
Phone:91 079 3001 3000
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
Email
Sumit.arora@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi Ahmedabad 380 015, India
Phone:91 079 3001 3000
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
General Manager
Affiliation
Veeda Clinical Research Ltd.
Address
Veeda Clinical Research Ltd.,
Shivalik Plaza, Near I.I.M.,
Ambawadi Ahmedabad 380 015, India
Phone:91 079 3001 3000
Paliperidone Palmitate (3-month) Extended Release Injectable Suspension for intramuscular use 546 mg (350 mg Paliperidone) (Pharmathen S.A., Greece)
Patients will be randomized who are already on Paliperidone palmitate 156 mg (100 mg Paliperidone) extended release injectable suspension every month therapy for atleast 4 months.
Comparator Agent
TREVICTA® 350 mg Prolonged Release Suspension for injection (Janssen-Cilag International NV, Belgium)
Patients will be randomized who are already on Paliperidone palmitate 156 mg (100 mg Paliperidone) extended release injectable suspension every month therapy for atleast 4 months
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male or non-pregnant, non-lactating females aged 18-65 years (inclusive) having a documented clinical diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V).
2. Written informed consent for participation in the study by the patient and patient’s legal acceptable representative (LAR) and willing to adhere to protocol requirements.
3. Patients having BMI between 18-35 kg / m2 and at least 50 kg weight for male patients and 48 kg for female patients.
4. Patients who at screening are at a stable regimen of oral Paliperidone or Risperidone therapy or who are already receiving Paliperidone palmitate 156 mg (100 mg Paliperidone) extended release injectable suspension and who at randomization are receiving a stable regimen of 156 mg (100 mg Paliperidone) of monthly paliperidone palmitate extended release suspension via the intramuscular route.
5. Patients who are clinically stable and not hospitalized for exacerbation of psychiatric symptoms for at least 3 months before randomization.
6. Patients having Clinical Global Impression scale score of ≤ 4 at both screening and Baseline visits.
7. Patients not having any significant diseases or clinically significant abnormal findings except schizophrenia during screening
8. Adequate organ and bone marrow function at screening and randomization defined by: Bone marrow function:
a) Total white blood cell count≥ 4000/mm3
b) ANC ≥1500/mm3
c) Platelet count ≥ 100,000/mm3
d) Hemoglobin ≥ 9gm/dl
Hepatic function: Bilirubin <1.5 X ULN
AST & ALT <5 X ULN
Renal function: Creatinine clearance more than or equal 80 mL per min (Calculated based on Cockcroft-Gault formula)
9. Patients able to comply with study procedures in the opinion of the investigator.
10. 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 the study and up to 90 days after the last PK sample collection. Cessation of birth control after this point should be discussed with a responsible physician.
11. Women of non child bearing potential with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy at least 6 months prior to IMP administration) or postmenopausal for at least 12 consecutive months.
OR
Women of child bearing potential must have negative pregnancy test at screening visit and before randomization and must agree to 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 IMP administration] sexual partner) for at least 4 weeks prior to IMP administration, during the study and up to 90 days after the last dose of IMP. Cessation of birth control after this point should be discussed with a responsible physician
Note: It is the investigator’s responsibility to ensure that the above points regarding an effective method of avoiding pregnancy are discussed with the patient/LAR in detail and patient agrees with this and this is documented in source document. The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per the protocol.
ExclusionCriteria
Details
1. Patients with known hypersensitivity/ intolerance to study drug or any other component of the drug or intolerance to oral paliperidone/risperidone prior to screening.
2. Patients with a history of Neuroleptic Malignant Syndrome (NMS) while on treatment with antipsychotics.
3. History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with use of drugs that prolong QTc interval, including: bradycardia, cardiac arrhythmias, hypokalemia or hypomagnesemia, concomitant use of other drugs that known to prolong the QTc interval, and prolonged QT interval (QTc> 450 msec in male patients or QTc> 470 msec in female patients, QTc interval to be calculated with Bazett’s Formula, at screening and randomization.
6. Patients with concurrent condition of Parkinsons disease except for drug-induced extrapyramidal syndrome. Patients with history or presence of tardive dyskinesia. Patients with cognitive and motor impairment.
7. 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.
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 and the first dose of study medication.
8. Treatment with any of the following therapies:
• Injection of risperidone long acting injection within 6 weeks before randomization.
• Electroconvulsive therapy within 3 months prior to screening.
• Clozapine within 3 months before screening
9. 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).
10. Patients with uncontrolled hypertension (systolic BP more than or equal to 150 mmHg/diastolic BP more than or equal to 100 mmHg).
11. Patients with known cerebrovascular disease, or conditions that predispose the patient to hypotension (e.g., dehydration, hypovolemia and treatment with antihypertensive medications).
12. Patients with inadequate mass in the deltoid regions to receive the intramuscular drug injection.
13. Patients with severe hepatic impairment based on the Child-Pugh classification (Child-Pugh category C).
14. Patients with a history of alcohol or drug-dependence as per DSM-V criteria during the 6-month period prior to screening.
15. Donation of blood (≥ 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 as clinically assessed by the investigator.
17. Patients found positive for HIV, Syphilis, Hepatitis B surface antigen or Hepatitis C antibody at screening.
18. A history of granulocytopenia, agranulocytosis or myeloproliferative disorders (drug-induced or idiopathic).
19. Patient positive on Breath alcohol analyzer test at the time of visit at screening and/or baseline.
20. Treatment with any investigational drug in the last 3 months (or 5 half-lives, whichever is longer) before signing the informed consent.
Note: Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study.
21. Psychosis judged to be the direct physiological effect of an abused medication or substance.
22. Patients with the following cardiac conditions:
• Recent myocardial infarction (<12 months)
• First-degree heart block with PR interval > 0.22 seconds.
• Sustained cardiac arrhythmia or history of sustained cardiac arrhythmia
• Uncompensated congestive heart failure, myocarditis, cardiomyopathy
• Complete left bundle branch block.
23. Patients with uncontrolled Diabetes mellitus (HbA1c more than or equal to 9 %)
24. A history of epilepsy or multiple syncopal episodes. Patients with seizures or other conditions that potentially lower the seizure threshold.
25. Patients with hyperprolactinemia or with possible prolactin dependent tumor at screening visit which as judged by the Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
26. Patients with dementia related psychosis.
27. Concurrent use of other drugs known to suppress bone marrow function.
28. Patients with ongoing clinically significant adverse event(s) due to prior treatments administered, as determined by the investigator.
29. Patients who, in the opinion of the Investigator, will not be compliant with the requirements of the study procedures.
30. History of difficulty in accessibility of veins or intolerance to direct venipuncture.
31. Positive on urine test for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine, and morphine) prior to receiving the first dose of investigational medicinal product in the study.
32. Patients who are on active treatment with drugs that are known to interact with paliperidone (List of Allowed and Prohibited Medications Provided in Appendix IV).
Note: If the patient was on any of the prohibited medications outlined in Appendix IV, sufficient wash out period (of at least 5 half-lives) must have elapsed since the last dose of such drug and the first dose of study medication.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of the Test Product Paliperidone palmitate (3-month) extended release injectable suspension for intramuscular use 546 mg (350 mg Paliperidone) with respect to the Reference Product TREVICTA®350 mg prolonged release suspension for injection in adult schizophrenic patients.
A total of 42 blood samples each of 03 mL will be collected from each patient for PK assessment during the study.All the post-dose PK blood samples till 48.00 hr. should be collected within ± 2 minutes from the scheduled sampling time.
Secondary Outcome
Outcome
TimePoints
To monitor the safety and tolerability profile of the two formulations.
AtScreening, Day 46 ± 7 days ,Day 136 ± 7 days ,Day 226 ± 7 days, at each dosing and EOS visit, there will be physical examination,vitals signs will be performed by investigator.
Target Sample Size
Total Sample Size="284" Sample Size from India="284" 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
Upon entering into the study, patients will receive the Injection Paliperidone
Palmitate extended release injectable suspension for intramuscular use 546 mg
(350 mg Paliperidone) Intra muscularly (Deltoid site) every 3 months for a
total of 4 doses at ambient temperature as per randomization schedule (either the test or
reference product) in a parallel design.Investigational product administration will be done by
the trained study personnel under the supervision of the investigator.
During the Stabilization period, patients will receive monthly-doses
of an approved marketed version of paliperidone palmitate 156 mg (100 mg
Paliperidone) extended release injectable suspension. Details of the same will be included in
IMP plan.
After the study is completed (after last PK
sample collection on Day 361), patients may be continued on their current
dose of Paliperidone using an approved paliperidone product as prescribed
by their clinicians.
Administration shall be performed on alternating body sides (left and
right) for each injection.