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

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.

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