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

NCT ID: NCT02431702

Last Updated: 2025-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 337 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-08
• Study Completion Date: 2019-11-12

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.

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. Healthy controls (comparable in age, sex, race, and highest parental education to the treated participants) were recruited at each of the 3 MRI centers as controls for the MRI machine calibration for the duration of the study. These healthy controls were to undergo MRI assessments, but were not otherwise involved with the study and did not receive study medication. No safety or efficacy data were collected for these healthy controls.

Conditions

Schizophrenia; Psychotic Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

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

Haloperidol

Intervention Type: DRUG

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

Olanzapine

Intervention Type: DRUG

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

Oral Paliperidone ER

Intervention Type: DRUG

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

Perphenazine

Intervention Type: DRUG

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

Quetiapine

Intervention Type: DRUG

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

Oral Risperidone

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Paliperidone Palmitate Injection (PP1M)

Intervention Type: 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.

Paliperidone Palmitate Injection (PP3M)

Intervention Type: 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: OAP

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

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

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

Haloperidol

Intervention Type: DRUG

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

Olanzapine

Intervention Type: DRUG

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

Oral Paliperidone ER

Intervention Type: DRUG

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

Perphenazine

Intervention Type: DRUG

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

Quetiapine

Intervention Type: DRUG

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

Oral Risperidone

Intervention Type: DRUG

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

Part-3: PP - PP

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

Group Type: EXPERIMENTAL

Paliperidone Palmitate Injection (PP3M)

Intervention Type: 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-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.

Group Type: EXPERIMENTAL

Paliperidone Palmitate Injection (PP1M)

Intervention Type: 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.

Paliperidone Palmitate Injection (PP3M)

Intervention Type: 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-3: OAP - OAP

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

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

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

Haloperidol

Intervention Type: DRUG

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

Olanzapine

Intervention Type: DRUG

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

Oral Paliperidone ER

Intervention Type: DRUG

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

Perphenazine

Intervention Type: DRUG

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

Quetiapine

Intervention Type: DRUG

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

Oral Risperidone

Intervention Type: DRUG

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

Interventions

Aripiprazole

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

Intervention Type: DRUG

Haloperidol

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

Intervention Type: DRUG

Olanzapine

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

Intervention Type: DRUG

Oral Paliperidone ER

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

Intervention Type: DRUG

Perphenazine

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

Intervention Type: DRUG

Quetiapine

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

Intervention Type: DRUG

Oral Risperidone

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Scientific Affairs, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Scientific Affairs, LLC

Locations

Little Rock, Arkansas, United States

Garden Grove, California, United States

Lemon Grove, California, United States

Los Angeles, California, United States

San Diego, California, United States

San Rafael, California, United States

Stanford, California, United States

Lauderdale Lakes, Florida, United States

Leesburg, Florida, United States

Miami, Florida, United States

Tampa, Florida, United States

West Palm Beach, Florida, United States

Chicago, Illinois, United States

Granite City, Illinois, United States

Hoffman Estates, Illinois, United States

Indianapolis, Indiana, United States

Louisville, Kentucky, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

East Lansing, Michigan, United States

Grand Rapids, Michigan, United States

Muskegon, Michigan, United States

Omaha, Nebraska, United States

Albuquerque, New Mexico, United States

Cedarhurst, New York, United States

Rochester, New York, United States

Staten Island, New York, United States

Charlotte, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Eugene, Oregon, United States

Philadelphia, Pennsylvania, United States

Houston, Texas, United States

Bothell, Washington, United States

Itapira, , Brazil

Rio de Janeiro, , Brazil

São José, , Brazil

México, , Mexico

Countries

United States; Brazil; Mexico

References

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.

Reference Type: DERIVED

PMID: 37756123 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37004331 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35939921 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35247794 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

R092670SCH3013

Identifier Type: OTHER

Identifier Source: secondary_id

CR106193

Identifier Type: -

Identifier Source: org_study_id