A Study of the Efficacy (Effectiveness) of Paliperidone Palmitate in the Prevention of Recurrence of the Symptoms of Schizophrenia.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of paliperidone palmitate compared with placebo in the prevention of recurrence of the symptoms of schizophrenia and to assess the safety and tolerability of paliperidone palmitate in patients with stable and symptomatic schizophrenia. The placebo used in this study was a nutritional substance known as 20% Intralipid emulsion given to patients requiring intravenous feedings.

Detailed Description
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Many patients with schizophrenia have difficulty adhering to a daily oral treatment regimen. Long-acting injectable formulations, such as long-acting injectable paliperidone palmitate, may provide therapeutic plasma concentrations over several weeks, thereby eliminating the need for daily oral medication and making compliance easier. This study is a randomized (patients will be assigned to different treatment groups based solely on chance), double-blind (neither the patient nor the physician will know if placebo or drug is being given and at what dose), placebo-controlled, parallel-group, multicenter study followed by an open-label extension period in patients with schizophrenia. The study is designed to evaluate the efficacy of paliperidone palmitate (a long-acting injectable formulation) in delaying the time to and decreasing the rate of recurrence compared with placebo in patients with schizophrenia. The study will consist of 5 periods: an up to 7-day screening/washout/tolerability period, a 9-week open-label transition period, a 24-week open-label maintenance period, a randomized, variable-length double-blind, placebo-controlled recurrence prevention period, and an up to 52-week open-label extension period. Patients will have intramuscular (i.m.) study drug injections and efficacy and safety evaluations performed every 4 weeks throughout the study. Efficacy will be evaluated during the study using a recurrence assessment, the Positive and Negative Symptom Scale for Schizophrenia (PANSS), the Clinical Global Impression - Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Safety will be assessed throughout the study by monitoring adverse events; use of extrapyramidal symptoms (EPS) rating scales (Abnormal Involuntary Movement Scale [AIMS], Barnes Akathisia Rating Scale [BARS], Simpson Angus Scale [SAS]); clinical laboratory testing; vital signs (temperature, blood pressure, and heart rate) measurements; electrocardiograms (ECGs); and physical examinations. Additionally, the patients will assess the tolerability of the injections by evaluating the pain of the injection and the pain at the injection sites. Tolerability test: 3 mg/day of oral ER OROS paliperidone for 4 days. Transition (9 wks): 50 mg eq. paliperidone palmitate i.m. dose on Day 1, then i.m. injections (25, 50, or 100 mg eq.) once every 4 wks (q4wk). Maintenance (24-wks): paliperidone palmitate i.m. injections (25, 50, or 100 mg eq.) q4wk. Recurrence Prevention: paliperidone palmitate i.m. injections (25, 50, or 100 mg eq. or placebo) q4wk. Open-label paliperidone palmitate (25, 50, 75, or 100 mg eq.) q4wk for 12 dosing periods.

Official Title
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A Randomized Double-blind Placebo-controlled Parallel Group Study Evaluating Paliperidone Palmitate in the Prevention of Recurrence in Patients With Schizophrenia. Placebo Consists of 20% Intralipid (200 mg/mL) Injectable Emulsion.

Conditions
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Schizophrenia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet the diagnostic criteria for schizophrenia according to DSM-IV-TM for at least 1 year before screening have a PANSS score of <120 have a body mass index (BMI) >/=15.0 kilogram (kg)/meter (m)2 and have resided at the same address for at least 30 days Exclusion Criteria: Patients unable to provide their own consent have been involuntarily committed to psychiatric hospitalization have primary, active DSM-IV-TM diagnosis other than schizophrenia who have a DSM-IV-TM diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary) have a history of treatment resistance as defined by failure to respond to 2 adequate trials (minimum of 4 weeks at a therapeutic dose) of different antipsychotic medications have a history of any severe preexisting gastrointestinal narrowing or inability to swallow the medication whole with water have a history of neuroleptic malignant syndrome (NMS) are at significant risk of suicidal or violent behavior current presence of any significant or unstable medication condition treatment with any protocol disallowed therapies clinically significant result from screening laboratory or ECG.

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>Paliperidone Palmitate 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo | Drug: Paliperidone Palmitate<br>* 25, 50, 75 or 100 mg eq every 4 wk for up to 24 mo<br>|
| Placebo Comparator: 002<br>Placebo Placebo every 4 wk up to 24 mo | Drug: Placebo<br>* Placebo every 4 wk up to 24 mo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy criteria for this study is the time from randomization to the first recurrence event during the double-blind recurrence prevention period |  | After 68 relapse events | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from randomization to the end of the recurrence prevention period in PANSS (total and subscales), CGI-S, and PSP. Incidence of adverse events, labs and ECGs throughout study. |  | After 68 relapse events | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone palmitate, R092670, antipsychotic, recurrence prevention