A Bioequivalence in Patients with Schizophrenia already receiving a stable Regimen of Paliperidone Palmitate Extended Release Injectable Suspension.

Not yet recruiting

• Conditions: Schizophrenia, unspecified,

• Registration Number: CTRI/2021/06/034105
• Lead Sponsor: Accord Healthcare Inc

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."

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-06
• Last Update Posted: 2024-04-25

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.	Pre-dose- Dose 1 (Day 1), Dose 2 (Day 91), Dose 3 (Day 181) and Dose 4 (Day 271) | Post-Dose for Dose 4: 24.0 (Day 272), 96.0 (Day 275), 168.0 (Day 278), 267.0 (Day 282), 360.0 (Day 286), 456.0 (Day 290), 552.0 (Day 294), 600.0 (Day 296), 648.0 (Day 298), 696.0 (Day 300), 744.0 (Day 302), 792.0 (Day 304), 840.0 (Day 306), 936.0 (Day 310), 1032.0 (Day 314), 1152.0 (Day 319), 1320.0 (Day 326), 1488.0 (Day 333), 1656.0 (Day 340), 1824.0 (Day 347), 1992.0 (Day 354) and 2160.0 (Day 361)

Secondary Outcome Measures

Name	Time	Method
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:
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

Trial Locations

Locations (22)

Adichunchanagiri Hospital & Research Centre; 🇮🇳 Mandya, KARNATAKA, India

Ahana Hospitals LLP; 🇮🇳 Madurai, TAMIL NADU, India

Anand Multispeciality Hospital & Research Centre; 🇮🇳 Gandhinagar, GUJARAT, India

Athma Hospital And research Pvt Ltd; 🇮🇳 Tiruchirappalli, TAMIL NADU, India

Chethana Centre for Neuropsychiatric Rehabilitation; 🇮🇳 Kozhikode, KERALA, India

Divine Multispeciality Hospital; 🇮🇳 Gandhinagar, GUJARAT, India

Divyam Hospital; 🇮🇳 Surat, GUJARAT, India

Divyam Hospital, Palsana, Surat; 🇮🇳 Surat, GUJARAT, India

G S V M Medical College Kanpur; 🇮🇳 Nagar, UTTAR PRADESH, India

JSS Medical College and Hospital; 🇮🇳 Mysore, KARNATAKA, India

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Adichunchanagiri Hospital & Research Centre

🇮🇳Mandya, KARNATAKA, India

Dr Vinay H R

Principal investigator

9980038331

drvinayhr@bgsaims.edu.in