Study to Measure the Safety of Paliperidone ER (Extended-release) in Patients With Liver Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the tolerability and safety of paliperidone ER (extended-release) in doses between 3 milligrams per day and 12 milligrams per day in the treatment of patients with schizophrenia or schizoaffective disorder and liver disease.

Detailed Description
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Patients with schizophrenia or schizoaffective disorder commonly have other conditions that may affect the liver, such as alcohol abuse and/or chronic liver infections (hepatitis). Although single-dose studies in patients with liver disease are conducted to test the safety of medications, there is less information about the safety of treatment with medications for schizophrenia in this at-risk population of patients with schizophrenia or schizoaffective disorder and liver disease. This 9-week study is open-label (both patient and investigators know what study drug and dose of study drug the patient is taking) and has 2 phases. During Phase 1, which lasts 4 weeks, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual). During the first week of Phase 2, patients will receive decreasing doses of TAU and increasing doses of paliperidone ER. For the rest of Phase 2, which lasts 4 more weeks, patients will take paliperidone ER in doses between 3 mg/day and 12 mg/day, as prescribed by the study doctor. This study will evaluate adverse events and will use several scales and tests to measure the effectiveness of paliperidone ER in patients with an established diagnosis of schizophrenia or schizoaffective disorder and liver disease. Study assessments include the PANSS (Positive and Negative Symptom Scale for Schizophrenia), CGI (Clinical Global Impression scale), MSQ (Medication Satisfaction Questionnaire), sleep VAS (Visual Analog Scale), SF-36 (Short Form 36 Health Survey), and PSP (Personal and Social Performance Scale). Each assessment will be performed at least two times during the course of the study, but some assessments will be done more frequently. Visits are scheduled every 1 to two weeks during the 9 week study. The hypothesis is that paliperidone ER can be used safely in patients with schizophrenia or schizoaffective disorder who also have identified liver disease. During Phase 1 of the study, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual) for 4 weeks. For the first week of Phase 2, patients will receive decreasing doses of TAU. During Phase 2, patients will take paliperidone ER in doses between 3 milligrams per day and 12 milligrams per day by mouth for 5 weeks.

Official Title
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A Single-arm Evaluation of the Safety of Paliperidone Extended-Release (ER) in Subjects With Schizophrenia or Schizoaffective Disorder With Hepatic Disease

Conditions
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Schizophrenia, Schizoaffective Disorder, Psychotic Disorders

Intervention / Treatment
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* Drug: Treatment as usual (TAU), Paliperidone ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women must be postmenopausal for at least 1 year, surgically sterile, abstinent, or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study, and must also have a negative urine pregnancy test at Screening Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder Must have identified current, stable liver disease (e.g., viral hepatitis, alcoholic cirrhosis) Child-Pugh class A or B (total score < 10) Exclusion Criteria: Not able to swallow the study medication whole with the aid of water Not currently meeting criteria for any other Axis I diagnosis, including a DSM-IV diagnosis of Bipolar Disorder Not using alcohol in the previous 2 weeks or meeting the DSM-IV criteria for substance abuse or dependence or alcohol abuse or dependence in the 6 months before study entry Not experiencing severe liver disease or an acute exacerbation of the underlying liver disease (Child-Pugh total score >=10) No evidence of severe hepatic decompensation within the previous 3 months, such as: ascites not controlled with diuretics, peritonitis, portal hypertension or gross hepatic encephalopathy (eg, somnolence, stupor, coma)

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Treatment as usual (TAU), Paliperidone ERTreatment as usual is the subject's current antipsychotic and doses for 4 weeks; TAU AND Paliperidone ER - per site investigator for 1 week; Paliperidone ER 6mg once daily for 1 week; Paliperidone ER-3 to 12mg tablets once daily for 4 weeks | Drug: Treatment as usual (TAU), Paliperidone ER<br>* Treatment as usual is the subject's current antipsychotic and doses for 4 weeks; TAU AND Paliperidone ER - per site investigator for 1 week; Paliperidone ER 6mg once daily for 1 week; Paliperidone ER-3 to 12mg tablets once daily for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Adverse Event summary for both serious adverse events and other adverse events. Please see the Clinical Study Report Synopsis for results on this primary outcome measure or the AE section for a detailed breakdown of each adverse event preferred term in both categories. | Day 1 - Day 62 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | The PANSS is a 30-item scale (range 30-210) 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 (1=Absent, 2=Minimal, 3=Mild, 4=Moderate, 5=Moderate/Severe, 6=Severe, 7=Extreme).The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. | Day 1 - Day 62 | 
| Clinical Global Impression of Severity (CGI-S) Change From Baseline | The CGI-S (range 1-7) is a standardized, clinician-rated assessment to rate the severity of illness of the patient. The clinician assessed the severity of illness using the following categories: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill. The minimum score is 1 and maximum score is 7, with higher scores indicating more severe illness. | Day 1 - Day 62 | 
| Personal and Social Performance Score (PSP) Change From Baseline | The PSP (range 1-100) is a validated clinician-rated assessment of functioning. Four areas of functioning (socially useful activities, personal/social relationships, self-care, disturbing/aggressive behaviors) are assessed on a 6-point scale (0=absent to 5=very severe). A transformed score from 1 to 100 is generated from the raw score based on the clinical interpretation of the scores generated in the 4 areas of functioning, with a higher transformed score indicating better function. | Day 1 - Day 62 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antipsychotic, paliperidone ER, liver disease, Schizophrenia, Schizoaffective Disorder, Invega