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
Condition: Schizophrenia; Psychotic Disorders
MeSH terms: Disease Progression; Schizophrenia; Mental Disorders; Psychotic Disorders
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Aripiprazole; Haloperidol; Olanzapine; Oral Paliperidone ER; Perphenazine; Quetiapine; Oral Risperidone; Paliperidone Palmitate Injection (PP1M); Paliperidone Palmitate Injection (PP3M)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Aripiprazole will be administered in accordance with the label or Investigator's discretion; Haloperidol will be administered in accordance with the label or Investigator's discretion; Olanzapine will be administered in accordance with the label or Investigator's discretion; Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.; Perphenazine will be administered in accordance with the label or Investigator's discretion; Quetiapine will be administered in accordance with the label or Investigator's discretion; Risperidone tablets 1-6 mg per day will be administered orally.; 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) 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 MeSH terms: Haloperidol; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Paliperidone Palmitate; Haloperidol decanoate; Perphenazine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Paliperidone Palmitate; Oral Antipsychotics; Schizophrenia; Psychotic Disorders; Cognition in Schizophrenia; Brain intracortical myelin volume; Personal and Social Performance; Disease Modification