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

NCT02431702 | Completed Phase 3 Results

• 2 other identifiers: CR106193R092670SCH3013
• Study Type: interventional
• Target: 337
• Locations: 3 countries
• Sites: 38

Brief Summary

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.

Conditions

Schizophrenia; Psychotic Disorders

Keywords

Paliperidone Palmitate; Oral Antipsychotics; Schizophrenia; Psychotic Disorders; Cognition in Schizophrenia; Brain intracortical myelin volume; Personal and Social Performance; Disease Modification

Outcome Measures

Primary Outcomes (3)

• Part-2 (Disease Progression): Time to First Treatment Failure

  Treatment failure is defined as the time from participant's randomization to first treatment failure, which was a composite endpoint consisting of any of the following: 1) Psychiatric hospitalization due to worsening symptoms; 2) Any deliberate self-injury, suicidal ideation or behavior, homicidal ideation or violent behavior that is clinically significant and needs immediate intervention as determined by the study physician; 3) New arrest/incarceration; 4) Discontinuation of antipsychotic treatment due to inadequate efficacy as determined by the study physician; 5) Discontinuation of antipsychotic treatment due to safety or tolerability as determined by the study physician; 6) Treatment supplementation with another antipsychotic due to inadequate efficacy as determined by the study physician; 7) Increase in the level of psychiatric services in order to prevent imminent psychiatric hospitalization as determined by the study physician.

  From Day 1 up to 9 Months

• Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

  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. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

  Baseline and 18 Months

• Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

  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. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning.

  Baseline and Day 260

Secondary Outcomes (28)

• Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

  Baseline and Month 9

• Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

  Baseline and Month 9

• Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

  Baseline and Day 260

• Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain

  Baseline and Day 260

• Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain

  Baseline and Day 260

Study Arms (6)

Part-1: Oral Antipsychotics (OAP)

ACTIVE COMPARATOR

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; Drug: Haloperidol; Drug: Olanzapine; Drug: Oral Paliperidone ER; Drug: Perphenazine; Drug: Quetiapine; Drug: Oral Risperidone

Part-2: Paliperidone Palmitate (PP)

EXPERIMENTAL

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); Drug: Paliperidone Palmitate Injection (PP3M)

Part-2: OAP

ACTIVE COMPARATOR

Participants who will complete Part-1 will be randomized to receive Oral Antipsychotics for 9 months.

Drug: Aripiprazole; Drug: Haloperidol; Drug: Olanzapine; Drug: Oral Paliperidone ER; Drug: Perphenazine; Drug: Quetiapine; Drug: Oral Risperidone

Part-3: PP - PP

EXPERIMENTAL

Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.

Drug: Paliperidone Palmitate Injection (PP3M)

Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)

EXPERIMENTAL

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); Drug: Paliperidone Palmitate Injection (PP3M)

Part-3: OAP - OAP

ACTIVE COMPARATOR

Participants who will complete Part-2 (with OAP treatment) will be randomized to receive OAP treatment for additional 9 months.

Drug: Aripiprazole; Drug: Haloperidol; Drug: Olanzapine; Drug: Oral Paliperidone ER; Drug: Perphenazine; Drug: Quetiapine; Drug: Oral Risperidone

Interventions

Aripiprazole DRUG

Aripiprazole will be administered in accordance with the label or Investigator's discretion

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Haloperidol DRUG

Haloperidol will be administered in accordance with the label or Investigator's discretion

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Olanzapine DRUG

Olanzapine will be administered in accordance with the label or Investigator's discretion

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Oral Paliperidone ER DRUG

Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Perphenazine DRUG

Perphenazine will be administered in accordance with the label or Investigator's discretion

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Quetiapine DRUG

Quetiapine will be administered in accordance with the label or Investigator's discretion

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Oral Risperidone DRUG

Risperidone tablets 1-6 mg per day will be administered orally.

Part-1: Oral Antipsychotics (OAP); Part-2: OAP; Part-3: OAP - OAP

Paliperidone Palmitate Injection (PP1M) DRUG

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.

Part-2: Paliperidone Palmitate (PP); Part-3: OAP - Delayed Start Paliperidone Palmitate (PP)

Paliperidone Palmitate Injection (PP3M) DRUG

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.

Part-2: Paliperidone Palmitate (PP); Part-3: OAP - Delayed Start Paliperidone Palmitate (PP); Part-3: PP - PP

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: lead

Study Sites (38)

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Little Rock, Arkansas, United States

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Garden Grove, California, United States

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Lemon Grove, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Rafael, California, United States

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Stanford, California, United States

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Lauderdale Lakes, Florida, United States

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Leesburg, Florida, United States

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Miami, Florida, United States

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Tampa, Florida, United States

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West Palm Beach, Florida, United States

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Chicago, Illinois, United States

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Granite City, Illinois, United States

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Hoffman Estates, Illinois, United States

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Indianapolis, Indiana, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Worcester, Massachusetts, United States

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East Lansing, Michigan, United States

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Grand Rapids, Michigan, United States

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Muskegon, Michigan, United States

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Omaha, Nebraska, United States

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Albuquerque, New Mexico, United States

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Cedarhurst, New York, United States

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Rochester, New York, United States

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Staten Island, New York, United States

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Charlotte, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Eugene, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Houston, Texas, United States

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Bothell, Washington, United States

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Itapira, Brazil

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Rio de Janeiro, Brazil

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São José, Brazil

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México, Mexico

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Related Publications (4)

• Lopena OJ, Alphs LD, Sajatovic M, Turkoz I, Sun L, Johnston KL, Sliwa JK, Najarian DM, Starr HL. Earlier Use of Long-Acting Injectable Paliperidone Palmitate Versus Oral Antipsychotics in Patients With Schizophrenia: An Integrated Patient-Level Post Hoc Analysis. J Clin Psychiatry. 2023 Sep 25;84(6):23m14788. doi: 10.4088/JCP.23m14788.

  PMID: 37756123 DERIVED

• Tishler TA, Ellingson BM, Salvadore G, Baker P, Turkoz I, Subotnik KL, de la Fuente-Sandoval C, Nuechterlein KH, Alphs L. Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study. Schizophr Res. 2023 May;255:195-202. doi: 10.1016/j.schres.2023.03.023. Epub 2023 Mar 31.

  PMID: 37004331 DERIVED

• Alphs L, Baker P, Brown B, Fu DJ, Turkoz I, Nuechterlein KH. Evaluation of major treatment failure in patients with recent-onset schizophrenia or schizophreniform disorder: A post hoc analysis from the Disease Recovery Evaluation and Modification (DREaM) study. Schizophr Res. 2022 Oct;248:58-63. doi: 10.1016/j.schres.2022.07.015. Epub 2022 Aug 6.

  PMID: 35939921 DERIVED

• Alphs L, Brown B, Turkoz I, Baker P, Fu DJ, Nuechterlein KH. The Disease Recovery Evaluation and Modification (DREaM) study: Effectiveness of paliperidone palmitate versus oral antipsychotics in patients with recent-onset schizophrenia or schizophreniform disorder. Schizophr Res. 2022 May;243:86-97. doi: 10.1016/j.schres.2022.02.019. Epub 2022 Mar 2.

  PMID: 35247794 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Aripiprazole; Haloperidol; Olanzapine; Paliperidone Palmitate; Perphenazine; Quetiapine Fumarate; Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Butyrophenones; Ketones; Organic Chemicals; Benzodiazepines; Benzazepines; Isoxazoles; Azoles; Pyrimidines; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Dibenzothiazepines; Thiazepines; Thiepins; Pyrimidinones

Limitations and Caveats

The treatment failure (TF) definition for this study was very broad. For example, the TF reason, supplementation with another antipsychotic, was biased against PP as supplementing with oral paliperidone or risperidone was considered a TF which is usual clinical practice. Supplementation was the most common first TF criteria for PP. A designated individual of the subject was a requirement for study inclusion which may have also contributed to increased OAP adherence in the beginning of the study.

Results Point of Contact

• Title: Senior Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Scientific Affairs, LLC Clinical Trial

  Janssen Scientific Affairs, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2015
• First Posted: May 1, 2015
• Study Start: July 8, 2015
• Primary Completion: November 12, 2019
• Study Completion: November 12, 2019
• Last Updated: April 29, 2025
• Results First Posted: January 19, 2021

Record last verified: 2025-04

Locations

ME (1); BR (3); US (34)