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

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

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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: paliperidone palmitate; Drug: aripiprazole; Drug: haloperidole; Drug: olanzapine; Drug: paliperidone; Drug: perphenazine; Drug: quetiapine; Drug: risperidone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 4

Contacts and Locations

Study Locations

• Puerto Rico
  • Rio Piedras, Puerto Rico
• United States
  • Arizona
    • Bullhead City, Arizona, United States
    • Tuscon, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Anaheim, California, United States
    • Escondido, California, United States
    • Glendale, California, United States
    • Imperial, California, United States
    • Long Beach, California, United States
    • National City, California, United States
    • Oakland, California, United States
    • Oceanside, California, United States
    • Pico Rivera, California, United States
    • Riverside, California, United States
    • San Bernadino, California, United States
    • San Diego, California, United States
    • San Fran Cisco, California, United States
  • Connecticut
    • New Britain, Connecticut, United States
    • New London, Connecticut, United States
  • Florida
    • Leesburg, Florida, United States
    • Miami, Florida, United States
    • Miami Gardens, Florida, United States
    • Pensacola, Florida, United States
    • Tamarac, Florida, United States
    • Tampa, Florida, United States
  • Hawaii
    • Honolulu, Hawaii, United States
  • Illinois
    • Chicago, Illinois, United States
    • Hoffman Estates, Illinois, United States
    • Naperville, Illinois, United States
    • Springfield, Illinois, United States
  • Kansas
    • Wichita, Kansas, United States
    • Witchita, Kansas, United States
  • Louisiana
    • New Orleans, Louisiana, United States
    • Shreveport, Louisiana, United States
  • Mississippi
    • Flowood, Mississippi, United States
  • Missouri
    • Kansas City, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • Paramus, New Jersey, United States
    • Willingboro, New Jersey, United States
  • New York
    • Buffalo, New York, United States
    • New York, New York, United States
  • Ohio
    • Cleveland, Ohio, United States
    • Middleburg Heights, Ohio, United States
    • Willoughby, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • Pennsylvania
    • Allentown, Pennsylvania, United States
    • Philadelphia, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Desoto, Texas, United States
    • Irving, Texas, United States
    • San Antonio, Texas, United States
    • Wharton, Texas, United States
  • Washington
    • Bothell, Washington, United States
    • Spokane, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 001; paliperidone palmitate 78 117 156 or 234 mg monthly injection for 15 months	Drug: paliperidone palmitate; 78, 117, 156, or 234 mg monthly injection for 15 months
ACTIVE_COMPARATOR: 002; aripiprazole flexible dosing as prescribed by the study doctor for 15 months	Drug: aripiprazole; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 003; haloperidole flexible dosing as prescribed by the study doctor for 15 months	Drug: haloperidole; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 004; olanzapine flexible dosing as prescribed by the study doctor for 15 months	Drug: olanzapine; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 005; paliperidone flexible dosing as prescribed by the study doctor for 15 months	Drug: paliperidone; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 006; perphenazine flexible dosing as prescribed by the study doctor for 15 months	Drug: perphenazine; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 007; quetiapine flexible dosing as prescribed by the study doctor for 15 months	Drug: quetiapine; flexible dosing as prescribed by the study doctor for 15 months
ACTIVE_COMPARATOR: 008; risperidone flexible dosing as prescribed by the study doctor for 15 months	Drug: risperidone; flexible dosing as prescribed by the study doctor for 15 months

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC

Publications and helpful links

General Publications

• Bell Lynum KS, Henderson DC, Wright HJ, Gogate JP, Kim E. Treatment Effect With Paliperidone Palmitate Compared With Oral Antipsychotics in Black/African American Patients With Schizophrenia and a History of Criminal Justice System Involvement: A Post Hoc Analysis of the PRIDE Study. J Clin Psychiatry. 2021 Feb 23;82(2):20m13356. doi: 10.4088/JCP.20m13356.
• Alphs L, Mao L, Lynn Starr H, Benson C. A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia. Schizophr Res. 2016 Feb;170(2-3):259-64. doi: 10.1016/j.schres.2015.12.012. Epub 2015 Dec 29.
• Alphs L, Bossie C, Mao L, Lee E, Starr HL. Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement. Early Interv Psychiatry. 2018 Feb;12(1):55-65. doi: 10.1111/eip.12271. Epub 2015 Sep 25.
• Alphs L, Benson C, Cheshire-Kinney K, Lindenmayer JP, Mao L, Rodriguez SC, Starr HL. Real-world outcomes of paliperidone palmitate compared to daily oral antipsychotic therapy in schizophrenia: a randomized, open-label, review board-blinded 15-month study. J Clin Psychiatry. 2015 May;76(5):554-61. doi: 10.4088/JCP.14m09584.
• Alphs L, Mao L, Rodriguez SC, Hulihan J, Starr HL. Design and rationale of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study: a novel comparative trial of once-monthly paliperidone palmitate versus daily oral antipsychotic treatment for delaying time to treatment failure in persons with schizophrenia. J Clin Psychiatry. 2014 Dec;75(12):1388-93. doi: 10.4088/JCP.13m08965.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: May 3, 2010
• First Submitted That Met QC Criteria: July 1, 2010
• First Posted (ESTIMATE): July 7, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 7, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Schizophrenia; Aripiprazole; Risperidone; Paliperidone; Quetiapine; Paliperidone palmitate; Haloperidol; Olanzapine; Risperdal; Perphenazine
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Olanzapine; Aripiprazole; Paliperidone Palmitate; Quetiapine Fumarate; Risperidone; Perphenazine
• Other Study ID Numbers: CR015625; R092670SCH3006 (OTHER: Janssen Scientific Affairs, LLC)