A Phase 3 interventional study of Aripiprazole and Haloperidol in Schizophrenia and Psychotic Disorders, sponsored by Janssen Scientific Affairs, LLC. Completed at 38 sites in 3 countries. Open to participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-29.
Sponsored by Janssen Scientific Affairs, LLC (part of Johnson & Johnson) · Phase 3, Interventional, and Treatment
Among 115 studies testing paliperidone in Schizophrenia — 6 open to participants now, 6 under way, none of them phase 3. paliperidone · Schizophrenia.
Among the 115 studies testing paliperidone in Schizophrenia, this one is the 33rd largest by enrollment, is one of 6 that started in 2015, is one of 41 in phase 3, and was the 94th registered.
3,563 studies on the registry are indexed under Schizophrenia; 491 are open to participants now.
This study's enrollment of 337 is above the median of 71 across 2,944 interventional studies indexed under Schizophrenia.
Browse Schizophrenia studies →6 of the 115 studies testing paliperidone in Schizophrenia are open now, in 4 countries. Each count lists the studies.
paliperidone: first FDA approval 2006 (INVEGA), first EMA approval 2007. What it is approved for, and how studies give it, is on its page →
Of the 331 Schizophrenia studies recruiting now, 63 (19%) set no upper age limit and 257 (78%) stop at 75 or younger; 42 take children under 18; 83 take healthy volunteers.
This study: 18 Years to 35 Years · all sexes · healthy volunteers too.
The full table on the hub →115 studies; the count open now beside each. This study's row is marked.
First in 2003; this study’s year is marked. 6 started in 2015.
Median enrollment 178 across the 115 interventional studies. Of the 104 that completed or were terminated, 42 (40%) have results posted.
93 of 115 have an industry lead sponsor. The 10 most frequent:
Janssen Scientific Affairs, LLC is the lead sponsor of 41 studies on the registry; 2 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 4 (57%) have results posted.
Janssen Scientific Affairs, LLC has 5 studies filed under Schizophrenia — fewer than ten, so there is no comparison to draw.
2 of the studies testing paliperidone in Schizophrenia that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07493551CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.A Bioequivalence Study of PP3M in Patients With Schizophrenia | 2026-12-31 |
| NCT04478838Centre for Addiction and Mental Health"Extended" (Alternate Day) Antipsychotic Dosing | 2027-09-30 |
Among the 115 studies testing paliperidone in Schizophrenia, from their registry updates:
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.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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)
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
Participants who will complete Part-2 (with PP treatment) will continue to receive Paliperidone Palmitate for 9 months.
Drug: Paliperidone Palmitate Injection (PP3M)
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)
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
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): 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.
Time frame: Baseline and Month 9
Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. 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. Higher score indicate better performance.
Time frame: 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)
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving of participants. The range of reasoning and problem solving 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score 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.
Time frame: Baseline and Day 260
Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The score ranges from 1 to 7, where 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.
Time frame: Baseline, up to 9 Months of Part 2
Part 2 (Disease Progression): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS)
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). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline.
Time frame: Baseline, up to 9 Months
Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score
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). Total score ranges from 1 to 7. Higher score indicate improvement.
Time frame: Baseline and endpoint Part 2 (up to 9 Months)
Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. 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. Higher score indicate better performance.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
Time frame: Baseline and 18 Months
Part 3 (EDP): 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.
Time frame: From Day 1 Up to 18 Months
Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving score of participants. The range of reasoning and problem solving 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score 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.
Time frame: Baseline and 18 Months
Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The total score ranges from 1 to 7, where 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.
Time frame: Baseline, up to 18 Months
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS
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). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline.
Time frame: Baseline, up to 18 Months
Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score
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). Total score ranges from 1 to 7. Higher score indicate improvement.
Time frame: Baseline, up to 18 Months
Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe) in each of the 4 domains. Based on 4 domains there will be 1 transformed 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.
Time frame: Month 9 of Part 3
Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
Time frame: Baseline and Month 9 of Part 3
A total of 337 participants were enrolled out of which 273 were randomized and received study medication while 64 did not and served as healthy controls. Healthy controls underwent MRI assessments as controls for the MRI machine calibration. They did not receive study medication and no safety or efficacy data were collected.
| Milestone | Part 1-Run-in: Oral Antipsychotics (OAP) | Part 2-Paliperidone Palmitate (PP) | Part 2-OAP | Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | Part 3-OAP to OAP (EDP and Disease Modification) | Healthy Controls |
|---|---|---|---|---|---|---|---|
| Started | 273 | 0 | 0 | 0 | 0 | 0 | 64 |
| Completed | 239 | 0 | 0 | 0 | 0 | 0 | 32 |
| Not completed | 34 | 0 | 0 | 0 | 0 | 0 | 32 |
| Withdrew: Adverse event | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 11 | 0 | 0 | 0 | 0 | 0 | 23 |
| Withdrew: Withdrawal of consent | 9 | 0 | 0 | 0 | 0 | 0 | 6 |
| Withdrew: Other | 5 | 0 | 0 | 0 | 0 | 0 | 3 |
| Withdrew: Does not tolerate paliperidone er | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part 1-Run-in: Oral Antipsychotics (OAP) | Part 2-Paliperidone Palmitate (PP) | Part 2-OAP | Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | Part 3-OAP to OAP (EDP and Disease Modification) | Healthy Controls |
|---|---|---|---|---|---|---|---|
| Started | 0 | 78 | 157 | 0 | 0 | 0 | 0 |
| Completed | 0 | 52 | 128 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 26 | 29 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 5 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 6 | 13 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 11 | 8 | 0 | 0 | 0 | 0 |
| Withdrew: Assigned pp, but required oap | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Other | 0 | 2 | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Assigned oap, but required pp | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| Milestone | Part 1-Run-in: Oral Antipsychotics (OAP) | Part 2-Paliperidone Palmitate (PP) | Part 2-OAP | Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | Part 3-OAP to OAP (EDP and Disease Modification) | Healthy Controls |
|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 49 | 57 | 63 | 0 |
| Completed | 0 | 0 | 0 | 40 | 47 | 46 | 0 |
| Not completed | 0 | 0 | 0 | 9 | 10 | 17 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 2 | 3 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 1 | 0 | 5 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 5 | 6 | 6 | 0 |
| Withdrew: Other | 0 | 0 | 0 | 1 | 1 | 6 | 0 |
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.
| days | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part-2 (Disease Progression): Time to First Treatment Failure | NA (263.0 to NA) | NA (NA to NA) |
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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 1.6 ± 1.19 | 3.2 ± 1.11 |
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.
| T-score | Part 3- PP to PP | Part 3- OAP to PP (or Delayed-Start PP) | Part 3-OAP to OAP |
|---|---|---|---|
| Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | -0.7 ± 1.02 | -0.2 ± 0.95 | 0.5 ± 0.96 |
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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 2.0 ± 1.01 | 2.8 ± 0.73 |
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. 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. Higher score indicate better performance.
| units on a scale | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 2.5 ± 1.60 | 2.9 ± 1.13 |
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
| ratio | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| 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) | -0.001 ± 0.002 | -0.004 ± 0.001 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain | -0.2 ± 1.08 | -0.8 ± 0.77 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain | 1.3 ± 1.22 | 1.0 ± 0.85 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain | 1.8 ± 1.21 | 3.5 ± 0.87 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 3.2 ± 1.18 | 0.7 ± 0.85 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain | 1.3 ± 1.29 | 1.4 ± 0.93 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving of participants. The range of reasoning and problem solving 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 0.2 ± 1.16 | 2.8 ± 0.83 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score 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.
| T-score | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain | 0.3 ± 1.25 | 1.6 ± 0.89 |
The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The score ranges from 1 to 7, where 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.
| units on a scale | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.2 ± 1.06 | -0.3 ± 0.94 |
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). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline.
| Participants | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Hallucinations — Worsened | 7 | 19 |
| Hallucinations — Unchanged | 29 | 73 |
| Hallucinations — Improved | 14 | 33 |
| Delusions — Worsened | 10 | 20 |
| Delusions — Unchanged | 23 | 70 |
| Delusions — Improved | 17 | 35 |
| Disorganized Speech — Worsened | 2 | 13 |
| Disorganized Speech — Unchanged | 36 | 85 |
| Disorganized Speech — Improved | 12 | 27 |
| Abnormal Psychomotor Behavior — Worsened | 9 | 14 |
| Abnormal Psychomotor Behavior — Unchanged | 37 | 86 |
| Abnormal Psychomotor Behavior — Improved | 4 | 25 |
| Negative Symptoms — Worsened | 17 | 25 |
| Negative Symptoms — Unchanged | 16 | 61 |
| Negative Symptoms — Improved | 17 | 39 |
| Impaired Cognition — Worsened | 13 | 29 |
| Impaired Cognition — Unchanged | 22 | 52 |
| Impaired Cognition — Improved | 15 | 44 |
| Mania — Worsened | 1 | 7 |
| Mania — Unchanged | 47 | 107 |
| Mania — Improved | 2 | 11 |
| Depression — Worsened | 7 | 28 |
| Depression — Unchanged | 33 | 74 |
| Depression — Improved | 10 | 23 |
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). Total score ranges from 1 to 7. Higher score indicate improvement.
| units on a scale | Part-2: Paliperidone Palmitate (PP) | Part-2: OAP |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score | -0.2 ± 1.44 | 0.1 ± 1.16 |
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. 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. Higher score indicate better performance.
| units on a scale | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 7.5 ± 1.94 | 7.0 ± 1.82 |
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
| ratio | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI) | -0.001 ± 0.001 | -0.003 ± 0.001 |
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.
| days | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Time to First Treatment Failure | NA (NA to NA) | NA (376.0 to NA) |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain | -1.7 ± 1.24 | 0.7 ± 1.16 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain | 0.3 ± 1.24 | 0.8 ± 1.15 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain | 2.5 ± 1.32 | 4.9 ± 1.24 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 2.4 ± 1.46 | 0.7 ± 1.35 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain | 0.2 ± 1.42 | -0.2 ± 1.35 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving score of participants. The range of reasoning and problem solving 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 3.4 ± 1.46 | 4.7 ± 1.34 |
MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score 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.
| T-score | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain | -0.2 ± 1.36 | 1.4 ± 1.26 |
The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The total score ranges from 1 to 7, where 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.
| units on a scale | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.7 ± 0.14 | -0.7 ± 0.14 |
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). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline.
| Participants | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Hallucinations — Worsened | 3 | 8 |
| Hallucinations — Unchanged | 27 | 29 |
| Hallucinations — Improved | 11 | 10 |
| Delusions — Worsened | 6 | 10 |
| Delusions — Unchanged | 21 | 20 |
| Delusions — Improved | 14 | 17 |
| Disorganized Speech — Worsened | 2 | 3 |
| Disorganized Speech — Unchanged | 27 | 36 |
| Disorganized Speech — Improved | 12 | 8 |
| Abnormal Psychomotor Behavior — Worsened | 4 | 2 |
| Abnormal Psychomotor Behavior — Unchanged | 32 | 37 |
| Abnormal Psychomotor Behavior — Improved | 5 | 8 |
| Negative Symptoms — Worsened | 11 | 4 |
| Negative Symptoms — Unchanged | 11 | 22 |
| Negative Symptoms — Improved | 19 | 21 |
| Impaired Cognition — Worsened | 10 | 9 |
| Impaired Cognition — Unchanged | 14 | 23 |
| Impaired Cognition — Improved | 17 | 15 |
| Mania — Worsened | 0 | 3 |
| Mania — Unchanged | 40 | 39 |
| Mania — Improved | 1 | 5 |
| Depression — Worsened | 7 | 6 |
| Depression — Unchanged | 26 | 29 |
| Depression — Improved | 8 | 12 |
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). Total score ranges from 1 to 7. Higher score indicate improvement.
| units on a scale | Part 3-PP to PP | Part 3-OAP to OAP |
|---|---|---|
| Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score | 0.3 ± 0.18 | 0.4 ± 0.18 |
The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe) in each of the 4 domains. Based on 4 domains there will be 1 transformed 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.
| units on a scale | Part 3-PP to PP | Part 3- OAP to PP (or Delayed-Start PP) | Part 3-OAP to OAP |
|---|---|---|---|
| Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score | 67.6 ± 1.81 | 66.1 ± 1.70 | 66.6 ± 1.70 |
The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of "IR volume minus PD volume". 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression.
| ratio | Part 3-PP to PP | Part 3- OAP to PP (or Delayed-Start PP) | Part 3-OAP to OAP |
|---|---|---|---|
| Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI) | -0.7 ± 1.02 | -0.2 ± 0.95 | 0.5 ± 0.96 |
Collected over Up to 20 Months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1-Run-in: Oral Antipsychotics (OAP) | 0/273 (0%) | 10/273 (3.7%) | 116/273 (42.5%) |
| Part 2-Paliperidone Palmitate (PP) | 1/78 (1.3%) | 10/78 (12.8%) | 50/78 (64.1%) |
| Part 2-OAP | 0/157 (0%) | 19/157 (12.1%) | 89/157 (56.7%) |
| Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | 0/49 (0%) | 1/49 (2%) | 18/49 (36.7%) |
| Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | 0/57 (0%) | 3/57 (5.3%) | 34/57 (59.6%) |
| Part 3-OAP to OAP (EDP and Disease Modification) | 0/63 (0%) | 8/63 (12.7%) | 27/63 (42.9%) |
| Event | Part 1-Run-in: Oral Antipsychotics (OAP) | Part 2-Paliperidone Palmitate (PP) | Part 2-OAP | Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | Part 3-OAP to OAP (EDP and Disease Modification) |
|---|---|---|---|---|---|---|
| Psychotic DisorderPsychiatric disorders | 1/273 | 4/78 | 5/157 | 0/49 | 0/57 | 4/63 |
| SchizophreniaPsychiatric disorders | 3/273 | 3/78 | 6/157 | 0/49 | 0/57 | 1/63 |
| Suicidal IdeationPsychiatric disorders | 0/273 | 3/78 | 4/157 | 0/49 | 2/57 | 0/63 |
| Psychotic SymptomPsychiatric disorders | 1/273 | 0/78 | 3/157 | 0/49 | 0/57 | 2/63 |
| GangliogliomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/273 | 0/78 | 0/157 | 1/49 | 0/57 | 0/63 |
| Completed SuicidePsychiatric disorders | 0/273 | 0/78 | 0/157 | 0/49 | 1/57 | 0/63 |
| CatatoniaPsychiatric disorders | 0/273 | 0/78 | 0/157 | 0/49 | 0/57 | 1/63 |
| AstheniaGeneral disorders | 0/273 | 1/78 | 0/157 | 0/49 | 0/57 | 0/63 |
| Exposure Via InhalationInjury, poisoning and procedural complications | 0/273 | 1/78 | 0/157 | 0/49 | 0/57 | 0/63 |
| AgitationPsychiatric disorders | 0/273 | 1/78 | 0/157 | 0/49 | 0/57 | 0/63 |
| Event | Part 1-Run-in: Oral Antipsychotics (OAP) | Part 2-Paliperidone Palmitate (PP) | Part 2-OAP | Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) | Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) | Part 3-OAP to OAP (EDP and Disease Modification) |
|---|---|---|---|---|---|---|
| Weight IncreasedInvestigations | 44/273 | 22/78 | 50/157 | 7/49 | 9/57 | 5/63 |
| AnxietyPsychiatric disorders | 5/273 | 5/78 | 4/157 | 0/49 | 6/57 | 3/63 |
| InsomniaPsychiatric disorders | 9/273 | 4/78 | 9/157 | 5/49 | 6/57 | 4/63 |
| AkathisiaNervous system disorders | 10/273 | 7/78 | 8/157 | 0/49 | 4/57 | 0/63 |
| HeadacheNervous system disorders | 11/273 | 7/78 | 12/157 | 1/49 | 2/57 | 4/63 |
| SomnolenceNervous system disorders | 19/273 | 7/78 | 4/157 | 1/49 | 3/57 | 1/63 |
| FatigueGeneral disorders | 10/273 | 4/78 | 1/157 | 0/49 | 5/57 | 1/63 |
| TremorNervous system disorders | 6/273 | 1/78 | 7/157 | 2/49 | 5/57 | 2/63 |
| NauseaGastrointestinal disorders | 5/273 | 4/78 | 11/157 | 2/49 | 2/57 | 5/63 |
| Injection Site PainGeneral disorders | 4/273 | 6/78 | 2/157 | 0/49 | 0/57 | 0/63 |
| Age, Continuous(years) | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| Mean | 23.2 ± 4.38 |
| Sex: Female, Male(Participants) | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| Female | 60 |
| Male | 213 |
| Ethnicity (NIH/OMB)(Participants) | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| Hispanic or Latino | 95 |
| Not Hispanic or Latino | 173 |
| Unknown or Not Reported | 5 |
| Race/Ethnicity, Customized(Participants) | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 17 |
| Black or African American | 91 |
| Native Hawaiian or Other Pacific Islander | 2 |
| White | 124 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Other | 39 |
| Region of Enrollment(Participants) | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| BRAZIL | 40 |
| MEXICO | 26 |
| UNITED STATES | 207 |
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Studies of the drug tested here: Paliperidone
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