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A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform (DREaM)

This study is currently recruiting participants.
Verified November 2017 by Janssen Scientific Affairs, LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT02431702
First Posted: May 1, 2015
Last Update Posted: December 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen Scientific Affairs, LLC
  Purpose
The purpose of the study is to compare effectiveness of paliperidone palmitate (PP: paliperidone palmitate once-monthly and 3-month injections) versus oral antipsychotic (OAP [that is oral paliperidone extended release {ER}, oral risperidone, or another OAP]) in delaying time to treatment failure. The study will also evaluate changes in cognition, functioning, brain intracortical myelin (ICM) volume following treatment with PP compared with OAP in participants with recent-onset schizophrenia or schizophreniform disorder.

Condition Intervention Phase
Schizophrenia Psychotic Disorders Drug: Aripiprazole Drug: Haloperidol Drug: Olanzapine Drug: Oral Paliperidone ER Drug: Perphenazine Drug: Quetiapine Drug: Oral Risperidone Drug: Paliperidone Palmitate Injection (PP1M) Drug: Paliperidone Palmitate Injection (PP3M) Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Matched-Control, Randomized, Open-Label, Flexible-Dose, Study in Subjects With Recent-Onset Schizophrenia or Schizophreniform Disorder to Compare Disease Progression and Disease Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics

Resource links provided by NLM:


Further study details as provided by Janssen Scientific Affairs, LLC:

Primary Outcome Measures:
  • Part-2: Time to First Treatment Failure [ Time Frame: Up to Month 9 ]
    Time to first treatment failure will be the time from participant's randomization to the first treatment failure, which was a composite endpoint consisting of any of the following events: new 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.

  • Part-3: Change From Baseline in MATRICS Consensus Cognitive Battery (MCCB) Score [ Time Frame: Baseline up to Month 18 ]
    The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores.


Secondary Outcome Measures:
  • Part-2: Change From Baseline in MCCB Score [ Time Frame: Baseline up to Month 9 ]
    The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores.

  • Change From Baseline in Personal and Social Performance (PSP) Total Score [ Time Frame: Baseline up to Month 18 ]
    The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1, absent to 6, very severe) in each of the 4 domains. Based on 4 domains there will be 1 total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision.

  • Change From Baseline in Brain Intracortical Myelin (ICM) Volume [ Time Frame: Baseline up to Month 18 ]
    Intracortical myelin (ICM) volume is a potential biomarker of etiology and treatment response of schizophrenia, therefore is included in the study to evaluate disease progression and disease modification. Brain intracortical myelin (ICM) volume will be measured by inversion recovery (IR) and spin echo (SE) MRI.

  • Change From Baseline in Clinical Global Impression Severity (CGI-S) Score [ Time Frame: Baseline up to Month 18 ]
    The Clinical Global Impression Severity (CGI-S) rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher scores indicate worsening.

  • Change From Baseline in Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS) [ Time Frame: Baseline up to Month 18 ]
    The CRDPSS is an 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms. Each item on the measure is rated on a 5-point scale (0=none; 1=equivocal; 2=present, but mild; 3=present and moderate; and 4=present and severe).

  • Change From Baseline Medication Satisfaction Questionnaire (MSQ) Score [ Time Frame: Baseline up to Month 18 ]
    The Medication Satisfaction Questionnaire (MSQ) is a 7-point, verbally administered, Likert-type scale rated as follows: 1=Extremely Dissatisfied, 2=Very Dissatisfied, 3=Somewhat Dissatisfied, 4=Neither Satisfied Nor Dissatisfied, 5=Somewhat Satisfied, 6=Very Satisfied, 7=Extremely Satisfied. Worst value is 1 (Extremely Dissatisfied) and best value is 7 (Extremely Satisfied).

  • Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Baseline up to Month 18 ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.


Estimated Enrollment: 275
Actual Study Start Date: July 8, 2015
Estimated Study Completion Date: November 19, 2019
Estimated Primary Completion Date: July 20, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Part-1: Oral Antipsychotics (OAP)
All Participants will receive Paliperidone Extended Release (ER) 1.5 to 12 milligram (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Subjects who tolerate paliperidone ER/risperidone but find it inadequately efficacious after treatment for an adequate duration at an adequate dosage (per clinical judgment), may be switched to another protocol-specified OAP at the discretion of the investigator.
Drug: Aripiprazole
Aripiprazole will be administered in accordance with the label or Investigator's discretion
Drug: Haloperidol
Haloperidol will be administered in accordance with the label or Investigator's discretion
Drug: Olanzapine
Olanzapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Paliperidone ER
Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.
Drug: Perphenazine
Perphenazine will be administered in accordance with the label or Investigator's discretion
Drug: Quetiapine
Quetiapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Risperidone
Risperidone tablets 1-6 mg per day will be administered orally.
Experimental: Part-2: Paliperidone Palmitate (PP)
Participants who will complete Part-1 will be randomized to receive oral Paliperidone Palmitate (PP) treatment. Participants will receive 5 doses of PP1M (paliperidone palmitate once-monthly injection). First dose at a starting dose of 234 mg on Day 1 and thereafter second dose in second week and then, every month up to Day 92. Participants will be subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
Drug: Paliperidone Palmitate Injection (PP1M)
Participants will receive 5 doses of PP1M. First dose at a starting dose of 234 mg on Day 1 and a second dose of 156 mg on Day 8 and then 78 to 234 mg (in 3 flexible doses), every month up to Day 92.
Drug: Paliperidone Palmitate Injection (PP3M)
Paliperidone Palmitate injection (PP3M) will be administered once every 12 weeks intramuscularly. The initial dose will be calculated as 3.5 fold multiple of the final PP1M dose administered on Day 92 (or Day 176). Dose will be increased based on Investigator's discretion.
Active Comparator: Part-2: OAP
Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.
Drug: Aripiprazole
Aripiprazole will be administered in accordance with the label or Investigator's discretion
Drug: Haloperidol
Haloperidol will be administered in accordance with the label or Investigator's discretion
Drug: Olanzapine
Olanzapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Paliperidone ER
Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.
Drug: Perphenazine
Perphenazine will be administered in accordance with the label or Investigator's discretion
Drug: Quetiapine
Quetiapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Risperidone
Risperidone tablets 1-6 mg per day will be administered orally.
Experimental: Part-3: PP - PP
Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.
Drug: Paliperidone Palmitate Injection (PP3M)
Paliperidone Palmitate injection (PP3M) will be administered once every 12 weeks intramuscularly. The initial dose will be calculated as 3.5 fold multiple of the final PP1M dose administered on Day 92 (or Day 176). Dose will be increased based on Investigator's discretion.
Experimental: Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive PP treatment for 9 months. PP treatment includes PP1M and PP3M. Participants will be subsequently switched to PP3M following a minimum of 5 injections of PP1M. Participants receiving PP3M may go back to treatment with PP1M (monthly injections of 78, 117, 156 or 234 mg, flexibly dosed) for further dose adjustment or for the duration of the study with the approval of the medical monitor.
Drug: Paliperidone Palmitate Injection (PP1M)
Participants will receive 5 doses of PP1M. First dose at a starting dose of 234 mg on Day 1 and a second dose of 156 mg on Day 8 and then 78 to 234 mg (in 3 flexible doses), every month up to Day 92.
Drug: Paliperidone Palmitate Injection (PP3M)
Paliperidone Palmitate injection (PP3M) will be administered once every 12 weeks intramuscularly. The initial dose will be calculated as 3.5 fold multiple of the final PP1M dose administered on Day 92 (or Day 176). Dose will be increased based on Investigator's discretion.
Active Comparator: Part-3: OAP - OAP
Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.
Drug: Aripiprazole
Aripiprazole will be administered in accordance with the label or Investigator's discretion
Drug: Haloperidol
Haloperidol will be administered in accordance with the label or Investigator's discretion
Drug: Olanzapine
Olanzapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Paliperidone ER
Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.
Drug: Perphenazine
Perphenazine will be administered in accordance with the label or Investigator's discretion
Drug: Quetiapine
Quetiapine will be administered in accordance with the label or Investigator's discretion
Drug: Oral Risperidone
Risperidone tablets 1-6 mg per day will be administered orally.

Detailed Description:
A Prospective, matched-control, Randomized (assignment of study drug by chance), open-label, flexible-dose, study in participants with recent-onset schizophrenia or schizophreniform disorder to compare disease progression and disease modification following treatment with PP long-acting injection (once-monthly followed by 3-month injections) or OAP (Any of the following 7 OAPs are permitted: aripiprazole, haloperidol, olanzapine, paliperidone ER, perphenazine, quetiapine, and risperidone). The study consists of 3 parts. Part-1 (Oral Run-In Phase), Part-2 (Disease Progression) and Part-3 (Extended Disease Progression and Disease Modification) with unique endpoints. Screening period will be up to 4 Weeks. Duration of Parts will be as: 2 months for Part-1, 9 months for Part-2 and Part-3. All participants will initially receive oral paliperidone ER or oral risperidone in Part-1. After paliperidone/risperidone treatment in Part-1, participants will be randomized into 1:2 ratio to receive PP or OAP in Part-2. Participants who complete Part-2 will enter into Part-3 wherein OAP group participants of Part-2 will be re-randomized into 1:1 ratio to OAP-OAP group and OAP-PP group, and PP group will continue without further randomization. Treatment failures will be evaluated in Part-2 and Part-3 of the study. Also changes in cognition, functioning, brain intracortical myelin (ICM) volume will be evaluated in the study. Participants' safety will be monitored throughout.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participant must have a current diagnosis of schizophrenia (295.90) or schizophreniform disorder (295.40) as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and confirmed by the Structured Clinical Interview for DSM-5 Disorders (SCID) with a first psychotic episode within the last 24 months prior to the screening visit
  • Participant requires treatment with an antipsychotic medication
  • Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study
  • Participant must have available a designated individual (example, family member, significant other, friend) who has knowledge of the participant and is generally aware of the participants daily activities, and who agrees to let the study site personnel know of changes in the participants circumstances when the participant is not able to provide this information. The designated individual must sign an informed consent form
  • Participant is anticipated to have a stable place of residence for the duration of the trial

Exclusion Criteria:

  • Participant has a current DSM-5 diagnosis of dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, autistic disorder, or intellectual disabilities
  • Participant meets the DSM-5 definition of moderate or severe substance use disorder (except for nicotine) within 2 months prior to Screening
  • Participant has a history of neuroleptic malignant syndrome
  • Participant has received long-acting injectable (LAI) medication within 2 injection cycles prior to the Screening visit
  • Participant has mental retardation, defined as pre-morbid intelligence quotient (IQ) as measured by Wechsler Test of Adult Reading at Screening less than (<) 70
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02431702


Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

  Show 42 Study Locations
Sponsors and Collaborators
Janssen Scientific Affairs, LLC
Investigators
Study Director: Janssen Scientific Affairs, LLC Clinical Trial Janssen Scientific Affairs, LLC
  More Information

Additional Information:
Responsible Party: Janssen Scientific Affairs, LLC
ClinicalTrials.gov Identifier: NCT02431702     History of Changes
Other Study ID Numbers: CR106193
R092670SCH3013 ( Other Identifier: Janssen Scientific Affairs, LLC )
First Submitted: April 28, 2015
First Posted: May 1, 2015
Last Update Posted: December 4, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Scientific Affairs, LLC:
Paliperidone Palmitate
Oral Antipsychotics
Schizophrenia
Psychotic Disorders
Cognition in Schizophrenia
Brain intracortical myelin volume
Personal and Social Performance
Disease Modification

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Psychotic Disorders
Disease Progression
Schizophrenia Spectrum and Other Psychotic Disorders
Disease Attributes
Pathologic Processes
Risperidone
Paliperidone Palmitate
Antipsychotic Agents
Aripiprazole
Olanzapine
Quetiapine Fumarate
Haloperidol
Haloperidol decanoate
Perphenazine
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents