A Phase 4 Study to Evaluate Response to Treatment and Safety of Paliperidone Extended-Release in Participants With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the response to treatment and safety of paliperidone extended-release (mechanism to dissolve a drug over time in order to be released slower and steadier into the blood stream) in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

Detailed Description
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This is a non-randomized, single-arm, multi-center (conducted in more than one center) study to explore response to treatment and safety of flexible dose of paliperidone extended-release (ER) in participants with schizophrenia. During the study period, dose of paliperidone ER will remain within the range of 3 to 12 milligram per day and will be administered for 12 months. Both hospitalized and non-hospitalized participants may be included in the study. Participants may switch to any effective dose of paliperidone ER from any oral antipsychotic medication without dose adjustment or if required, cross-dose adjustment may be done. Maximum 4 weeks of switching period is allowed. Use of anticholinergic (opposing the actions of the acetylcholine, a neurotransmitter) drugs will not be restricted. Response to treatment will be evaluated primarily through total Personal and Social Performance (PSP) Scale. Participants' safety will be monitored throughout the study.

Official Title
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An Open-label, Single-arm, Multicenter, Phase IV Study to Evaluate the Response to Treatment and Safety of Flexible Dose Treatment With Extended-release Paliperidone in Patients With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Paliperidone extended-release (ER)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Schizophrenia diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Recent onset (less than 3 years after the first episode/hospitalization) schizophrenia but either not on antipsychotic medication for at least 3 months or in need of antipsychotic medication switches because of safety and/or lack of efficacy reasons To be considered physically healthy at Screening according to vital signs and physical examination findings. If there are abnormalities, they must be consistent with the underlying illness in the study population Women at postmenopausal state for at least 1 year; or undergone surgical sterilization, or for women with child-bearing status, should be willing to use an effective contraceptive method throughout the study Participants who are willing and capable to complete the questionnaires Exclusion Criteria: Use of clozapine, depot neuroleptics or risperidone within the last 3 months Any unstable clinical condition including clinically important abnormal laboratory findings Previous and current tardive dyskinesia (abnormal involuntary movements which primarily affect the extremities, trunk, or jaw) symptoms History of malignant neuroleptic syndrome To be considered carrying high risk regarding adverse effects, homicide and/or suicide

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone extended-release (ER)<br> | Drug: Paliperidone extended-release (ER)<br>* Paliperidone ER tablets will be administered orally once daily as flexible dose ranging from 3 to 12 milligram (mg) per day for 12 months. The recommended dose will be 6 mg once daily.<br>* Other names: Invega;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Total Personal and Social Performance (PSP) Score at Month 12 | The PSP is a clinician-rated scale that reflects social functioning in 4 domains of behavior (socially useful activities including work and study, personal and social relationships, self care, and disturbing and aggressive behaviors). The total score ranges from 1 to 100 (score of 71 to 100 will have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision) divided into 10 equal intervals to rate the degree of difficulty (i=absent to vi=very severe) in each of the 4 domains. | Baseline and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Global Assessment of Functioning (GAF) Score at Month 12 | The GAF is a 100-point tool to measure overall psychological, social and occupational functioning of adults. The higher score range (that is, 91 to 100) refers to a superior functioning in a wide range of activities, and absence of symptoms. The lower score range (that is, 1 to 10) refers to persistent danger of severely hurting self or others; or persistent inability to maintain minimum personal hygiene; or serious suicidal act with clear expectation of death. | Baseline and Month 12 | 
| Change from Baseline in Total Positive and Negative Syndrome Scale (PANSS) Score and Subscales Score at Month 12 | The PANSS is a scale which measures the severity of psychotic symptoms of schizophrenia. Score ranges from 30 to 210 where 30=best and 210=worst. The scale consists of three subscales: positive subscale (Range 7 to 49), negative subscale (Range 7 to 49) and general psychopathology subscale (Range 16 to 112), which measures from absent to extreme condition. Higher scores indicate worsening. | Baseline and Month 12 | 
| Change from Baseline in Short Form (SF)-36 Scale Score at Month 12 | The SF-36 is a survey that measures 8 domains of health including: physical functioning, role limitations due to physical health (role-physical), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems (role-emotional) and general mental health. Each item is scored on a range of 0 to 100. Worst value is 0 and best value is 100. | Baseline and Month 12 | 
| Change from Baseline in Percentage of Participants With Relapse at Month 12 | The relapse will be diagnosed if participants meet any of the following criteria on 2 consecutive evaluations conducted 3 to 5 days apart: Psychiatric hospitalization; increase in level of care necessary and 25 percent increase in total PANSS score from Baseline; significant clinical deterioration defined as a clinical global impression of change scale score of 6 (indicating much worse); deliberate self-injury; clinically significant suicidal or homicidal ideation; violent behavior resulting in significant injury to another person or property; exceeding the registered dose of drug. | Baseline and Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone, Invega