Pharmacokinetic study of two formulations of paliperidone palmitate extended-release injectable suspension in patients with schizophrenia.

Phase 1

Completed

• Conditions: Schizophrenia

• Registration Number: CTRI/2018/05/013703
• Lead Sponsor: Mylan Laboratories Limited

Brief Summary

The study is Randomized, Multicenter,Multiple-dose, Two-treatment, Single-period, Parallel, Steady StateBioequivalence Study of Paliperidone Palmitate Extended-Release InjectableSuspension in Subjects with Schizophrenia under Fasting Condition.

 This study will be initiated only afterobtaining the approvals of Institutional Ethics Committee (IEC) and clinicaltrial permission from the Drug Controller General of India (DCGI). The subjectsqualifying inclusion and exclusion criteria will be invited to participate inthis study.

 The recruitment will happen as perrandomization schedule. Subject will be randomized in a 1:1 ratio to Test orReference product.

 Subject willreceive either Mylan’s paliperidone palmitate extended-Release Injectablesuspension or Janssen’s INVEGA SUSTENNA® as per the randomization. Mainconclusion on the bioequivalence will be drawn based on the PK data obtainedduring last dosing interval.

Plasma concentrations of Paliperidone willbe measured by using a validated method.

 Statistical analysis of pharmacokineticparameters comparing test and reference products will be performed to assessbioequivalence.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-05-14
• Last Update Posted: 2019-05-24
• Study Completion: 2019-10-01

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

• Subjects who qualify for the study should meet the following inclusion criteria: 1.Men or non-pregnant, non-lactating females aged 18-65 years (inclusive) having clinical diagnosis of schizophrenia.
• 2.Subjects with Body Mass Index (BMI) less than or equal to 35 but greater than or equal to 18.
• 3.Subjects who are clinically stable and no hospitalization for exacerbation of psychiatric symptoms during 3 months before screening and randomization.
• 4.Subjects with adequate renal function defined as creatinine clearance (Cockcroft-Gault Equation,) more than or equal to 80 mL/min.
• 5.Adequate hematological parameters at screening and randomization defined by: •Total white blood cell count more than or equal to 4000/mm3 •ANC more than or equal to 1500/mm3 •Platelet count more than or equal to 100,000/mm3 •Hemoglobin more than or equal to 9.0 gm/dl 6.Adequate hepatic function at screening and randomization as defined by: •Bilirubin less than 1.5 X ULN •AST & ALT less than 5 X ULN 7.Agree to comply with the visit schedule and other requirements of the study.

Exclusion Criteria

• Subjects must not be enrolled in the study if they meet any one of the following criteria: 1.History of known hypersensitivity to paliperidone, risperidone, or to any excipients in study medications. 2.Subjects with dementia related psychosis. 3.Subjects with a history of Neuroleptic Malignant Syndrome (NMS) while on treatment with atypical antipsychotics. 4.History or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval 5.Subjects with known cardiovascular disease (e.g., heart failure, history of myocardial infarction or ischemia, conduction abnormalities), cerebrovascular disease, or conditions that predispose the subject to hypotension (e.g., dehydration, hypovolemia, and treatment with antihypertensive medications). 6.Subjects with clinically significant hyperprolactinemia or with possible prolactin dependent tumor. 7.History of severe hepatic impairment and drug induced leukopenia/ neutropenia/ agranulocytosis. 8.Subjects with Clinical Global Impression.
• Severity of illness (CGI-S) score of 5 or more. 9.Subjects with history or presence of tardive dyskinesia, seizures or other conditions that potentially lower the seizure threshold, idiopathic Parkinson’s disease, cognitive and motor impairment. 10.Subjects who are on active treatment with drugs that are known to interact with paliperidone. 11.Have a history of alcohol or drug-dependence as per DSM-V criteria during the 6-month period immediately prior to screening. 12.Subjects with clinically significant laboratory investigations as per the investigator’s judgment. 13.Attempted suicide within 12 months before screening or are at imminent risk of suicide or violent behaviour as clinically assessed by the investigator. 14.Treatment with any of the following therapies: •Injection of risperidone long acting injection within 6 weeks before screening. •Electroconvulsive therapy within 3months prior to screening. •Clozapine within 3 months before screening. •Nonselective or irreversible monoamine oxidase inhibitor (MAOI) antidepressants within 30 days before screening. •Other antidepressant agents, unless subject had been on a stable dose for at least 3 months before screening and plans on remaining on that same exact regimen for the entire duration of the study. •Mood stabilizers, including lithium and all anticonvulsants, beta-blockers, and anti-parkinsonian medication. Unless subjects on a stable dose for at least 3 months before screening and expect to remain on that same exact regimen throughout the duration of the study. 15.Subjects who are: •Pregnant •Breast feeding •Male or female of childbearing potential unwilling to use adequate methods of contraception throughout the study. •Subjects whom had major surgery within 4 weeks prior to study entry, or who have not recovered from prior major surgery, or whom have surgery scheduled during the course of the study. •Subjects with known positivity for human immunodeficiency virus (HIV), HBsAg or HCV. 16.Participation in any interventional clinical study within the past 90 days of randomization. 17.History of difficulty with donating blood or difficulty in accessibility of veins. 18.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study. 19.Any reason which, in the opinion of the Principal Investigator or Co-Investigator, would prevent the subject from safely participating in the study.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
To evaluate the bioequivalence of Mylan’s Paliperidone Palmitate extended-Release Injectable Suspension with Janssen’s INVEGA SUSTENNA® in subjects with schizophrenia.	After 24 Week ( post dose 6 total 19 PK sample assessment )

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of Paliperidone Palmitate Extended-Release Injectable Suspension of Mylan Laboratories Limited, India in subjects with schizophrenia.	To evaluate the safety and tolerability of Paliperidone Palmitate Extended-Release Injectable Suspension of Mylan Laboratories Limited, India in subjects with schizophrenia.

Trial Locations

Locations (15)

Divyam Hospital; 🇮🇳 Surat, GUJARAT, India

GSVM Medical College; 🇮🇳 Nagar, UTTAR PRADESH, India

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

Kanoria Hospital & Research Centre; 🇮🇳 Gandhinagar, GUJARAT, India

Lifepoint multispecialty Hospital; 🇮🇳 Pune, MAHARASHTRA, India

Medipoint Hospital Pvt. Ltd; 🇮🇳 Pune, MAHARASHTRA, India

MITR Foundation; 🇮🇳 Ahmadabad, GUJARAT, India

Noble Hospitals Pvt. Ltd; 🇮🇳 Pune, MAHARASHTRA, India

Old Govt. General Hospital; 🇮🇳 Krishna, ANDHRA PRADESH, India

Oyster & Pearl Hospitals; 🇮🇳 Pune, MAHARASHTRA, India

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Divyam Hospital

🇮🇳Surat, GUJARAT, India

Dr Timir Shah

Principal investigator

9825137443

drtcshah@gmail.com