An Efficacy and Safety Study of One Dosage of Paliperidone Extended Release (ER) in Treating Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of 1.5 mg/day dose of paliperidone Extended Release (ER) as compared with placebo when used to treat patients with schizophrenia.

Detailed Description
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Currently, treatment of acute symptoms in schizophrenia is less than ideal, up to one-third of patients with schizophrenia do not respond to current treatments, and poor drug tolerability can decrease a patient's ability to remain on treatment. Paliperidone ER doses in the range of 3 mg/day to 12 mg/day have been approved for the treatment of patients with schizophrenia. A lower dosage form of paliperidone ER be efficacious and may reduce the risk of certain adverse effects. This study will evaluate the efficacy of 1 fixed (ie, it does not change during the study) dosage of paliperidone ER (1.5 mg/day) compared with placebo. One fixed dosage of paliperidone ER (6.0 mg/day) will be given to some patients as an active (it has already been shown to have efficacy) control. This is a multicenter, double-blind (neither the patient nor the study-site personnel know which treatment the patient is receiving), randomized (patients are assigned to a treatment group by chance), placebo-controlled (some patients will receive placebo and no active drug), parallel-group (patients in all groups follow the same study design) study in adults who were diagnosed with schizophrenia at least 1 year before screening and who are experiencing an acute episode. The study starts with an up-to-5-day screening phase to find out if the patient is eligible for the study. The screening phase includes a 3- to 5-day washout (the medication dosage is tapered down and finally stopped) of any medications that are being taken by a patient but that are not allowed during the study. A 6-week double-blind treatment phase follows and finishes with an end-of-study visit. A post-study visit to collect additional safety data will be scheduled for 1 week after a patient receives his or her last dose of study drug. The length of the entire study is about 8 weeks. Patients who withdraw from the study before completing the double-blind treatment phase will complete the end-of-study visit procedures at the time they withdraw and the post-study visit 1 week after receiving their last dose of study drug. For all patients leaving the study, the investigator will make every effort to see that they receive adequate continuity of care. At baseline (the visit just before a patient takes the first dose of study drug), all patients will be randomly assigned to 1 of the 3 possible treatment groups to receive paliperidone ER 1.5 mg/day, paliperidone ER 6 mg/day, or placebo once daily for 6 weeks. Patients must be voluntary inpatients at the time of randomization, and they must remain in the hospital for a minimum of 8 days. Efficacy will be measured using the following rating scales: the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S), the Personal and Social Performance Scale (PSP), and the Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36). Safety will be evaluated using physical examinations, ECGs, clinical laboratory testing (hematology, serum chemistry, and urinalysis), testings for pregnancy, and monitoring for adverse events including extrapyramidal symptoms (EPS) using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Rating Scale (SAS). The study hypothesis is that Paliperidone ER at 1.5 mg per day will be effective in the treatment of schizophrenia as measured by the change in total PANSS score between baseline and endpoint in comparison with placebo. Oral paliperidone ER 1.5 mg or 6.0 mg tablets or matching oral placebo tablets taken once daily in the morning for 6 weeks.

Official Title
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A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed Dosage of 1.5 mg/Day of Paliperidone Extended Release (ER) in the Treatment of Subjects With Schizophrenia

Conditions
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Schizophrenia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (295.10, 295.20, 295.30, 295.60, 295.90) at least 1 year before screening Experiencing an acute episode with a total PANSS score at screening of between 70 and 120 Are otherwise physically healthy Agree to at least 8 days of voluntary hospitalization. Exclusion Criteria: Active comorbid DSM-IV axis I diagnosis other than schizophrenia (nicotine and caffeine dependence are not exclusionary) Treatment with antidepressants (unless a subject has been on a stable dosage for at least 3 months before baseline) other than monoamine oxidase inhibitors DSM-IV diagnosis of substance dependence within 6 months before screening evaluation (nicotine and caffeine dependence are not exclusionary) Any medical condition that could potentially alter the absorption, metabolism, or excretion of the study medication, such as Crohn's disease, liver disease, or renal disease Relevant history of any significant or unstable cardiovascular, respiratory, neurologic (including seizures or significant cerebrovascular), renal, hepatic, endocrine, or immunologic disease.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Paliperidone ER 1.5 mg tablet once daily for 6 weeks | Drug: Paliperidone ER<br>* 1.5 mg tablet once daily for 6 weeks<br>|
| Active Comparator: 002<br>Paliperidone ER 6 mg tablet once daily for 6 weeks | Drug: Paliperidone ER<br>* 6 mg tablet once daily for 6 weeks<br>|
| Placebo Comparator: 003<br>Placebo Once daily for 6 weeks | Drug: Placebo<br>* Once daily for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in PANSS Total Score at the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment). | The Positive and Negative Syndrome Scale (PANSS) is a tool used by psychiatrists to measure the symptoms of psychosis experienced by a patient with schizophrenia. It includes 30 items that produce a total score ranging from a minimum of 30 (indicating least severe symptoms of illness) to a maximum of 120 (indicating most severe symptoms of illness). A negative change in score from baseline to end point indicates improvement in the symptoms of illness. | Baseline, 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of the Double-blind Treatment Phase (Week 6 or the Last Assessment Obtained After the Baseline Assessment) in CGI-S | The Clinical Global Impression-Severity (CGI-S) rating scale is used by psychiatrists to rate the severity of a patient's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). The scale permits a global evaluation of the patient's condition at a given time. | Baseline, 6 weeks | 
| Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in PSP Score | The Personal and Social Performance (PSP) scale assesses the degree of difficulty (ranging from i [absent] to vi [very severe]) a patient exhibits over a 1-month period in socially useful activities, personal and social relationships, self care, and disturbing and aggressive behavior. The overall score ranges from 1 to 100. Patients with scores of 71 to 100 have a mild degree of difficulty; patients with scores from 31 to 70 have various degrees of disability; and patients with scores of 30 or less function so poorly as to require intensive supervision. | Baseline, 6 weeks | 
| Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Physical Component Summary Scale Score | The Medical Outcomes Study Short Form Health Survey-36 (MOS SF-36) is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 subscale scores: the Physical Component Summary and the Mental Component Summary. | Baseline, 6 weeks | 
| Change From Baseline to End Point (Week 6 or the Last Assessment After the Baseline Assessment) in MOS SF-36 Mental Component Summary Scale Score | The MOS SF-36 is a measure of patient-reported health status. It is a 36-item questionnaire measuring 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health). Each domain score ranges from 0 (worst) to 100 (best), with higher scores reflecting better health-related functional status. Two summary scale scores are computed based on weighted combinations of the 8 domain scores: the Physical Component Summary and the Mental Component Summary. | Baseline, 6 weeks | 

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