A Study of Paliperidone Palmitate 3 Month Formulation for the Treatment of Patients With 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 3 month formulation (PP3M) compared with placebo in delay of the time to first occurrence of relapse of the symptoms of schizophrenia.

Detailed Description
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This is a randomized (the study drug is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel group (each group of patients will be treated at the same time), placebo-controlled (an inactive substance is compared with a drug to test whether the drug has a real effect in a clinical trial) multicenter study. The study consists of 4 phases: a Screening Phase (up to 3 weeks); a 17-week flexible dose open-label Transition Phase (open-label phase means that all people know the identity of the intervention); a 12-week fixed dose open-label Maintenance Phase; and a randomized, double-blind, fixed dose, placebo-controlled relapse prevention phase (referred to as the Double-blind Phase). Patients who meet specific stabilization criteria will enter the Double-blind Phase at Week 29. Patients will be randomly assigned, in a 1:1 ratio, to receive either a fixed dose of PP3M or placebo. The Double-blind Phase will be of variable duration; patients will remain in the study until they experience a relapse event or meet discontinuation criteria.

Official Title
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A Randomized, Multicenter, Double-Blind, Relapse Prevention Study of Paliperidone Palmitate 3 Month Formulation for the Treatment of Subjects With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: PP3M 175 mg eq.
* Drug: PP3M 263 mg eq.
* Drug: PP3M 350 mg eq.
* Drug: PP3M 525 mg eq.
* Drug: Placebo (20% Intralipid emulsion)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with schizophrenia for more than 1 year A total score in the Positive and Negative Syndrome Scale (PANSS) < 120 Signed informed consent Women must not be pregnant, breastfeeding, and if capable of pregnancy must practice an effective method of birth control Men must agree to use a double-barrier method of birth control Be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs, and electrocardiogram (ECG) Exclusion Criteria: A diagnosis other than schizophrenia, e.g., dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia-related psychosis Relevant history or current presence of any significant or unstable medical condition(s) determined to be clinically significant by the Investigator (ie, obesity, diabetes, heart disease etc) A diagnosis of substance dependence within 6 months before screening History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia Clozapine use in the last 2 months when used for treatment-resistant or treatment-refractory illness Clinically significant findings in biochemistry, hematology, ECG or urinalysis results Any other disease or condition that, in the opinion of the investigator, would make participation not in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone palmitate 3-month (PP3M)<br> | Drug: PP3M 175 mg eq.<br>* Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.<br>Drug: PP3M 263 mg eq.<br>* Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.<br>Drug: PP3M 350 mg eq.<br>* Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.<br>Drug: PP3M 525 mg eq.<br>* Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo (20% Intralipid emulsion)<br>* Form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Relapse During the Double-Blind Phase | Time to relapse defined as the time between participant randomization into the double blind Phase and the first documentation of a relapse event. Median time to relapse was estimated by the Kaplan-Meier method. | Approximately Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item is rated 1 (absent) to 7 (extreme). The total score ranging from 30 to 210. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | 
| Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | The CGI-S rating scale is used to rate the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | 
| Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | The PSP scale measures personal and social functioning in the domains of: a) Socially useful activities, b) Personal and social relationships, c) Self-care, and d) Disturbing and aggressive behavior. The results of the assessment were converted to a numerical score which ranges from 1 to 100. A score lying between 71 and 100 indicates a mild degree of dysfunction; scores between 31 and 70 indicate varying degrees of difficulty, and a participant with a score of <=30 had functioning so poor that he or she required intensive supervision. | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, R092670, Paliperidone Palmitate, Paliperidone palmitate 3 month formulation (PP3M)