Evaluation of Effectiveness and Safety of Flexible-dose Paliperidone Extended Release in Patients With Schizoaffective Disorder.

Study Overview
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Brief Summary
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The purpose of this study is to measure the effectiveness and assess the safety of different dosages (from 3 mg/day to 12 mg/day) of the antipsychotic paliperidone extended-release (ER) in patients who are experiencing an acute episode of schizoaffective disorder.

Detailed Description
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Schizophrenia and schizoaffective disorder are closely related in terms of symptoms, coexisting conditions, and genetic risk. In previous studies in patients with schizophrenia, treatment with paliperidone extended-release (ER) improved psychotic symptoms, as well as mood symptoms evaluated by anxiety/depression and hostility/excitement Positive and Negative Symptoms of Schizophrenia (PANSS) factor scores. Therefore, paliperidone ER may also be effective in treating symptoms of schizoaffective disorder. Paliperidone's limited potential for drug-drug interaction is particularly important in this patient population, in which multiple drug therapy is relatively common. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo-controlled, parallel-group study is designed to examine the effectiveness and safety of paliperidone ER in adult patients with schizoaffective disorder who are experiencing an acute episode of this disorder. Patients in the study will be randomly assigned to 1 of 2 groups to receive 6 weeks of oral treatment with flexible dosages of paliperidone ER (3-12 mg/day) or with placebo. The primary efficacy outcome will be the change from baseline to Week 6, or the last post-randomization assessment during double-blind treatment (endpoint), in the PANSS total score. Safety will be assessed by monitoring adverse events, clinical laboratory testing, pregnancy testing, vital signs measurements, physical examination, administration of a 12-lead ECG, movement disorders side effect scales, and the InterSePT Scale for Suicidal Thinking. Patients may also choose to participate in a pharmacogenomic (DNA) analysis. The primary study hypothesis is that flexible-dose paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder. Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or paliperidone ER 6 mg/day. After day 4, dosages may be adjusted, at defined intervals, to a dosage between 3 mg/day and 12 mg/day, inclusive.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel- Group Study to Evaluate the Efficacy and Safety of Flexible-dose Paliperidone ER in the Treatment of Patients With Schizoaffective Disorder.

Conditions
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Schizoaffective Disorder, Psychotic Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Paliperidone ER
* Drug: Paliperidone ER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnostic and Statistical Manual - Fourth Edition (DSM-IV) diagnosis of schizoaffective disorder A total Positive and Negative Symptoms of Schizophrenia (PANSS) score of >= 60 A score of >= 16 on Young Mania Rating Scale (YMRS) or a score of >= 16 on the Hamilton Depression Rating Scale (HAM-D 21) Exclusion Criteria: A primary active mental illness diagnosis other than schizoaffective disorder Patients with first episode psychosis Active substance dependence within previous 6 months Treatment with clozapine within 6 months of randomization A history of treatment resistance, defined by failure to respond to 2 adequate trials of antipsychotic medication Pregnancy, breast-feeding, or planning to become pregnant

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Paliperidone ER (3-12mg/day in 3 mg/day increments for 6 weeks) | Drug: Paliperidone ER<br>* (3-12mg/day in 3 mg/day increments for 6 weeks)<br>|
| Experimental: 003<br>Paliperidone ER (3-12mg/day in 3 mg/day increments for 6 weeks) | Drug: Paliperidone ER<br>* (3-12mg/day in 3 mg/day increments for 6 weeks)<br>|
| Placebo Comparator: 002<br>Placebo for 6 weeks | Drug: Placebo<br>* for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at 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 that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | Baseline | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | 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 that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening. | The primary efficacy endpoint was the change from baseline to week 6 or the last post-randomization assessment during double-blind treatment in the PANSS total score. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Positive Syndrome Scale (range 7-49): Sum of scores for items 1-7 in positive subscale: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Negative Syndrome Scale (range 7-49): Sum of scores for items 1-7 in negative subscale: blunted effect, emotional withdrawal, poor rapport, passive apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | General Psychopathology (range 16-112): Sum of scores for somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Positive PANSS Factor Score (range 8-56): Sum of scores for items 1, 3, 5, and 6 in positive subscale: delusions, hallucinatory behavior, grandiosity, suspiciousness; item 7 in negative subscale: stereotyped thinking; and items 1, 9, and 12 in general psychopathology subscale: somatic concern, unusual thought content, lack of judgment, and insight. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Negative PANSS Factor Score (range 7-49): Sum of scores for items 1, 2, 3, 4, and 6 in negative subscale: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity; and items 7 and 16 in general psychopathology subscale: motor retardation, and active social avoidance. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Disorganized Thoughts PANSS Factor Score (range 7-49): Sum of scores for item 2 in positive subscale:Conceptual disorganization; item 5 in negative subscale:difficulty in abstract thinking; and items 5, 10, 11, 13, and 15 in general psychopathology subscale: mannerisms/posturing, disorientation, poor attention, disturbance of volition, and preoccupation. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Uncontrolled Hostility/Excitement PANSS Factor Score (range 4-28): Sum of scores for items 4 and 7 in positive subscale: excitement, hostility; and items 8 and 14 in general psychopathology subscale: uncooperativeness, and poor impulse control. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Anxiety/Depression PANSS Factor Score (range 4-28): Sum of scores for items 2, 3, 4, and 6 in general psychopathology subscale: Anxiety, Guilt feelings, Tension, Depression. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline | 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 subject. 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 subjects. Higher scores indicate worsening. | Baseline | 
| Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | 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 subject. 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 subjects. Higher scores indicate worsening. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 
| Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | The CGI-C rating scale is a 7 point global assessment that measures the clinician's impression of the change occurring in the illness over a course of treatment, relative to baseline. A rating of 4 is equivalent to No change. Ratings of <4 are equivalent to improvement and ratings of > 4 are equivalent to worsening. Higher scores indicate worsening. | Week 6 or the last post-randomization assessment during double-blind treatment | 
| Participants With Response | Response is defined as a 30% or more reduction from baseline PANSS total score and CGI-C score of <= 2 (CGI-C-SCA: Clinical Global Impression of Change for Schizoaffective Disorder). | Week 6 LOCF End Point | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizoaffective Disorder, antipsychotic, paliperidone, placebo