15 Month Study for Adults Who Have Been Diagnosed With Schizophrenia and Incarcerated

Study Overview
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Brief Summary
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The study will assess the use of paliperidone palmitate compared with oral antipsychotic treatment in delaying time to a protocol-defined treatment failure over 15 months, in patients diagnosed with schizophrenia who have been incarcerated.

Detailed Description
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The primary objective of this study is to compare the efficacy of paliperidone palmitate with oral antipsychotic treatment in delaying time to a protocol-defined treatment failure over 15 months, in patients diagnosed with schizophrenia who have been incarcerated. Protocol-defined treatment failure is defined as arrest, psychiatric hospitalization, increase in psychiatric services to prevent imminent hospitalization, discontinuation of antipsychotic treatment due to inadequate efficacy, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to safety or tolerability or completed suicide. Protocol was amended on March 15, 2011 to reflect changes in the inclusion/exclusion criteria as well as the study objectives. Patients will receive either paliperidone palmitate 78, 117, 156, or 234 mg monthly by injection for fifteen months OR oral aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, and risperidone at doses selected by the study doctor.

Official Title
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A Fifteen-month, Prospective, Randomized, Active-controlled, Open-label, Flexible Dose Study of Paliperidone Palmitate Compared With Oral Antipsychotic Treatment in Delaying Time to Treatment Failure in Adults With Schizophrenia Who Have Been Incarcerated

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: paliperidone
* Drug: risperidone
* Drug: haloperidole
* Drug: perphenazine
* Drug: aripiprazole
* Drug: quetiapine
* Drug: paliperidone palmitate
* Drug: olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to understand and sign the informed consent form approved by the Institutional Review Board (IRB) Must successfully answer all the questions on the Informed Consent quiz indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study Have a current diagnosis of schizophrenia Taking no more than 1 oral antipsychotic on the day before randomization Have been placed into custody at least twice with one of them leading to incarceration within the 24 months previous to study start, with the last release occurring within the 90 days before the first day of screening in the opinion of the investigator, may benefit from a change in their prior antipsychotic treatment Have available a designated individual (eg, family member, case manager, significant other, probation/parole officer) who has knowledge of the patient and is generally aware of the patient's daily activities, and who agrees to let the study site personnel know of changes in the patients circumstances when the patient is not able to provide this information, ie, arrests, protocol-defined hospitalizations, emergency room visits, becoming homeless, etc. Have either an address or phone number where they can be reached, or be accessible to the designated individual Must agree to receive regular injections for 15 months if randomly assigned to the paliperidone palmitate treatment group, or continue with oral study medication treatment for 15 months if randomly assigned to the oral antipsychotic treatment group Women must be postmenopausal (for at least 2 years), surgically sterile (hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or if sexually active, be practicing a highly effective method of birth control Exclusion Criteria: Allergies, hypersensitivity (anaphylaxis-type reaction), or intolerance to risperidone or paliperidone Actively abusing intravenous drugs within the past 3 months or have an opiate dependence disorder Have a positive urine drug screen test for barbiturates, cocaine, amphetamines, or opiates at screening Women who are pregnant or breast-feeding, or planning to become pregnant Have received injectable antipsychotic treatment within 2 injection cycles prior to screening Received treatment with clozapine within 3 months of screening Are at a high risk of violence in the next 15 months, in the opinion of the investigator who have a history of sex offenses including felony sex offenses, child molestation

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 001<br>paliperidone palmitate 78 117 156 or 234 mg monthly injection for 15 months | Drug: paliperidone palmitate<br>* 78, 117, 156, or 234 mg monthly injection for 15 months<br>|
| Active Comparator: 002<br>aripiprazole flexible dosing as prescribed by the study doctor for 15 months | Drug: aripiprazole<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 003<br>haloperidole flexible dosing as prescribed by the study doctor for 15 months | Drug: haloperidole<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 004<br>olanzapine flexible dosing as prescribed by the study doctor for 15 months | Drug: olanzapine<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 005<br>paliperidone flexible dosing as prescribed by the study doctor for 15 months | Drug: paliperidone<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 006<br>perphenazine flexible dosing as prescribed by the study doctor for 15 months | Drug: perphenazine<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 007<br>quetiapine flexible dosing as prescribed by the study doctor for 15 months | Drug: quetiapine<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|
| Active Comparator: 008<br>risperidone flexible dosing as prescribed by the study doctor for 15 months | Drug: risperidone<br>* flexible dosing as prescribed by the study doctor for 15 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Treatment Failure | Time to first treatment failure was the time from participant randomization to the first treatment failure, which was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event. | From date of randomization up to Month 15 | 
| Percentage of Participants in Each Event Category of First Treatment Failure | First treatment failure was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation (D/C) of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event. Percentage of participants who experienced treatment failure due to any event and for each specific category of event were assessed. | From date of randomization up to Month 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Psychiatric Hospitalization or Arrest/Incarceration | A time to parameter looking only at 2 component events of treatment failure: arrest or incarceration, and psychiatric hospitalization. An arrest was defined as the taking of a participant into custody by legal authority, for any reason. Incarceration was defined as involuntary confinement by an officer of the law. Psychiatric hospitalization was an inpatient psychiatric hospitalization that occurred due to the participant's clinically significant worsening of symptoms of schizophrenia. | From date of randomization up to Month 15 | 
| Change From Baseline in Personal and Social Performance (PSP) Total Score During Overall Treatment Duration | The PSP score assesses the degree of difficulty a participant exhibit over a 1 month period within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior. The investigators rate participants' degree of difficulty in each of the 4 domains using a 6-point Likert scale (from 0=absent to 5=very severe). The domain ratings were then transformed to PSP total score ranging from 1 to 100. Higher PSP total scores denote better functioning. A score between 71 and 100 represents normal to mild degree of dysfunction; a score between 31 and 70 represents varying degree of difficulty; and a score <=30 represents poor function that requires intensive supervision. | Baseline up to Month 15 | 
| Time to First Psychiatric Hospitalization | A time-to parameter looking only at 1 component event of treatment failure: psychiatric hospitalization. Time to first psychiatric hospitalization was admission date of the psychiatric hospitalization recorded in the Assessment of Treatment Failure - Psychiatric Hospitalization. | From date of randomization up to Month 15 | 
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Overall Treatment Duration | The CGI-S rating scale was a 7-point global assessment of symptom severity with scores determined by clinician as follows: 1=Not ill, 2=Very Mild, 3= Mild, 4= Moderate, 5= Marked, 6= Severe, and 7= Extremely Severe. The higher the score the worse the illness. | Baseline up to Month 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Risperidone, Risperdal, Paliperidone palmitate, Aripiprazole, Haloperidol, Olanzapine, Paliperidone, Perphenazine, Quetiapine