A Study to Evaluate the Effect of Oral Paliperidone Extended-Release and Oral Risperidone Immediate-Release on Cognitive Function in Clinically Stable Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to compare the effect of oral paliperidone extended-release and oral risperidone immediate-release on cognitive function, especially the category fluency of Cognitive Abilities Screening Instrument, Chinese version (CASI C-2.0), in patients with an established diagnosis of schizophrenia.

Detailed Description
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This is a 28-week, randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), active-controlled (patients are assigned to either a recognized effective treatment or the study medication) comparative study. All patients will enter a run-in period to receive a stable therapeutic dose of oral risperidone immediate-release for at least 4 weeks. After the 4-week run-in period, patients will be randomly assigned to either remain on oral risperidone immediate-release (IR) or to receive a therapeutic dose of oral paliperidone extended-release (ER) and patients will be prospectively followed for a 24-week treatment phase. The treatment phase is composed of a 4-week flexible dose period followed by a 20-week stable dose period. During the 4-week flexible dose period, the dose of paliperidone ER or risperidone IR may be increased or decreased for each patient if clinically indicated (eg, significant side effects emerge or there is evidence of a lack of efficacy). At the end of 4-week flexible dose period, the final dose should be maintained for the 20-week fixed-dose period. Efficacy and safety will be assessed at baseline (Week 0) and Weeks 4, 12, and 24.

Official Title
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A Randomized, Open-Label, Study To Evaluate The Effect of Oral Paliperidone Extended-Release and Oral Risperidone Immediate-Release on Selected Cognitive Domains in Clinically Stable Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Paliperidone extended-release
* Drug: Risperidone immediate-release


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with schizophrenia Cognitive abilities screening instrument C-2.0 total score between 50 and 85 (inclusive) at baseline Baseline positive and negative syndrome scale score between 60 and 85 (inclusive) Clinical global impression-severity change less than or equal to 1 in the month prior to randomization Patients on a stable therapeutic dose of oral risperidone IR (between 3-6 mg/day) for at least 4 weeks prior to randomization Exclusion Criteria: Treatment refractory patients, defined as failure of more than or equal to 2 adequate trials of second generation antipsychotic treatment for schizophrenia History of neuroleptic malignant syndrome Allergy or hypersensitivity to risperidone or paliperidone, or to any of the excipients of oral risperidone IR or paliperidone ER tablets Participants who have taken paliperidone ER in the past Participants who have been treated with clozapine or any long-acting injectable (depot) antipsychotic within 3 months before randomization

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone extended-release<br> | Drug: Paliperidone extended-release<br>* Patients will receive 6 mg to 12 mg of paliperidone extended-release tablet once daily orally.<br>* Other names: Paliperidone;|
| Active Comparator: Risperidone immediate-release<br> | Drug: Risperidone immediate-release<br>* Patients will receive 3 mg to 7 mg of risperidone immediate-release tablet orally.<br>* Other names: Risperidone IR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in category fluency score of cognitive function scale (Cognitive Abilities Screening Instrument, Chinese version [CASI C-2.0]) from baseline to Week 24 | CASI C-2.0 will be used to measure patient's cognitive ability. The range of CASI score is 0 to 100 (a higher score indicating better performance and is influenced by patient's educational level). The CASI C-2.0 provides quantitative assessment on 9 cognitive domains and 20 questions, including attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, category fluency, abstraction, and judgment. | Baseline (Week 0), Week 4, Week 12 and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 24 in score of Modified Wisconsin Card Sorting Test (MWCST) short version | The WCST was developed to assess abstract reasoning and ability to shift cognitive strategies in response to environmental changes. The materials consist of a pack of 4 stimulus cards and 48 response cards which are devised so that each card contains from 1 to 4 identical figures of a single color. Individually administered, it requires the patient to sort the cards according to different principles (ie, by color, form, or number). As the test progresses, there are unannounced shifts in the sorting principle which require the patient to alter his or her approach. | Baseline, Week 4, Week 12 and Week 24 | 
| Change from baseline in score of Continuous Performance Test (CPT) | CPT is an attention test. Response patterns on the CPT II is used as an aid in monitoring treatment effectiveness. For example, some response patterns suggest inattentiveness or impulsivity, while other response patterns may indicate activation/arousal problems or difficulties maintaining vigilance. | Baseline, Week 4, Week 12 and Week 24 | 
| Change from baseline in score of Personal and Social Performance (PSP) scale | The PSP is a clinician-rated instrument providing an overall rating of personal and social functioning in subjects with schizophrenia on a scale of 1-100. Four domains of functioning are considered in the rating: 1) socially useful activities, including work and study, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. | Baseline, Week 4, Week 12 and Week 24 | 
| Change from baseline in score of Positive and Negative Syndrome Scale (PANSS) | The PANSS is a medical scale used for measuring symptom severity of patients with schizophrenia. The neuropsychiatric symptoms of schizophrenia will be assessed using the 30-item PANSS scale, which provides a total score (sum of the scores of all 30 items). Each scale is rated 1 (absent) to 7 (extreme). | Baseline, Week 4, Week 12 and Week 24 | 
| Change from baseline in score of Clinical Global Impression-severity (CGI-S) scale | The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the patient's condition at a given time. | Baseline, Week 4, Week 12 and Week 24 | 
| Change from baseline in score of Medication Satisfaction Questionnaire (MSQ) | MSQ is designed to assess treatment satisfaction among patients with schizophrenia. It consists of 1 question: Overall, how satisfied are you with your current antipsychotic medication(s)? with responses assessed on a 7-point scale rated as follows: 1=extremely dissatisfied, 2=very dissatisfied, 3=somewhat dissatisfied, 4=neither satisfied nor dissatisfied, 5=somewhat satisfied, 6=very satisfied, and 7=extremely satisfied. | Baseline, Week 4, Week 12 and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone, Risperidone, Paliperidone extended-release (ER), Risperidone immediate-release (IR)