An Efficacy and Safety Study of Paliperidone Extended-Release (ER) Tablets 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 tolerability, safety and treatment response of flexible doses of paliperidone extended-release (ER; designed to slowly release a drug in the body over an extended period of time) tablets in participants with acute 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 an open-label (all people know the identity of the intervention), single-arm (getting one dose of medicine), multi-center (conducted in more than 1 center) study to evaluate tolerability, safety and efficacy of flexible daily doses of paliperidone ER in participants with acute schizophrenia. All participants will be given paliperidone ER once daily at a dose of 3, 6, 9, or 12 milligram (mg) tablets orally depending on Investigator's discretion, based on participant's clinical response and tolerability towards paliperidone ER. The duration of the core phase of the treatment will be 6 weeks and the participants who will complete this phase, respond well and would like to continue, will be eligible to be enrolled in an extension phase, which is no longer than 12 months. Efficacy will primarily be evaluated by treatment response evaluated through total Positive and Negative Syndrome Scale (PANSS) score. Participants' safety will be monitored throughout the study.

Official Title
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Tolerability, Safety and Treatment Response of Flexible Doses of Paliperidone ER in Acutely Exacerbated Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Paliperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for schizophrenia Must be experiencing an acute schizophrenic episode with a Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal to 70 at Baseline Must be admitted to hospital for treatment of the acute schizophrenic episode and must agree for voluntary hospitalization for at least the first 7 days of the study Female participants must be postmenopausal (for at least 1 year), surgically sterile, abstinent, or, if sexually active, be practicing and effective method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study and female participants of child-bearing potential must have a negative urine pregnancy test at Screening Participants or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Exclusion Criteria: Pregnant or breast-feeding female participants First antipsychotic treatment ever Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment and on clozapine or a long-acting injectable antipsychotic during the last 3 months Known hypersensitivity to paliperidone extended-release (ER) or risperidone Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic diseases, history or current symptoms of tardive dyskinesia or neuroleptic malignant syndrome including recent or present clinically relevant laboratory abnormalities (as deemed by the Investigator) and participants with current or known history (over the past 6 months) of substance dependence according to DSM-IV Criteria

Ages Eligible for Study
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Minimum Age: 18 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<br>* Paliperidone ER tablet in flexible daily dose of 3, 6, 9 or 12 milligram (mg) as per Investigators' discretion will be given once daily orally for 6 weeks in the core treatment phase and no longer than 12 months in the extension phase after the completion of core treatment phase.<br>* Other names: Invega;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Response Based on Total PANSS Scale Score | Response was defined as decrease of at least 30 percent in total Positive and Negative Syndrome Scale (PANSS) score from Baseline to endpoint of core phase (which is, Day 42 or early discontinuation). The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, & poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of sum of all 30 PANSS items & ranges from 30 to 210. Higher scores indicate worsening. | Day 42 or early discontinuation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Positive and Negative Symptom Scale (PANSS) Score at Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) | The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data. | Baseline, Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Day 42 and Final Evaluation (Day 42 or Early Discontinuation) | The PANSS is a 30-item scale to assess neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Positive symptoms subscale consists of 8 items with total score range of 8-56; negative symptoms and disorganized thoughts subscale, consists of 7 items with total score range of 7-49, uncontrolled hostility/excitement (H/E) subscale and anxiety/depression subscale, each consists of 4 items with total score range of 4-28. Higher score indicates greater severity. Final evaluation is the last post-baseline visit with data. | Baseline, Day 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Percentage of Participants With Treatment Response Greater Than (>) 20 Percent, 40 Percent and 50 Percent in Total Positive and Negative Syndrome Scale (PANSS) Score | The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data. | Day 2, 3, 4, 5, 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Change From Baseline in Clinical Global Impression -Severity (CGI-S) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) | The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to normal, not at all ill and a rating of 7 is equivalent to among the most extremely ill participants. Higher scores indicate worsening. Final evaluation is the last post-baseline visit with data. | Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Change From Baseline in Personal and Social Performance Scale (PSP) Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) | The PSP assesses the degree of dysfunction within 4 domains of behavior: socially useful activities, personal & social relationships, self-care & disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 6, very severe) in each of 4 domains. Participants with a score of 71 to 100 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. Final evaluation is the last post-baseline visit with data. | Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Change From Baseline in Quality of Sleep Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) | The sleep evaluation scale is a self-administered scale that rates quality of sleep. Participants indicate on an 11-point scale that how well they have slept within the previous 7 days, score ranged from 0 (very badly) to 10 (very well). Final evaluation is the last post-baseline visit with data. | Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Change From Baseline in Day Time Drowsiness Evaluation Score at Day 7, 14, 28, 42 and Final Evaluation (Day 42 or Early Discontinuation) | The day time drowsiness evaluation scale is a self-administered scale that rates day time drowsiness. Participants indicate on an 11-point scale that how often they have felt drowsy within the previous 7 days, score ranged from 0 (not at all) to 10 (all the time). Final evaluation is the last post-baseline visit with data. | Baseline, Day 7, 14, 28, 42 and Final Evaluation (Day 42 or early discontinuation) | 
| Number of Participants Satisfied With the Study Treatment | Treatment satisfaction with paliperidone ER was assessed by the Investigator and participant on a 5-point scale: 1 (very good), 2 (good), 3 (reasonable), 4 (moderate) and 5 (poor), at the end of the core treatment phase (which is, Day 42 or early discontinuation) by conducting an interview. | Day 42 or early discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone Extended Release (ER), Invega