Schizophrenia, Psychotic Disorders
Conditions
Keywords
Paliperidone Palmitate, Oral Antipsychotics, Schizophrenia, Psychotic Disorders, Cognition in Schizophrenia, Brain intracortical myelin volume, Personal and Social Performance, Disease Modification
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.
Interventions
DRUGAripiprazole
Aripiprazole will be administered in accordance with the label or Investigator's discretion
DRUGHaloperidol
Haloperidol will be administered in accordance with the label or Investigator's discretion
DRUGOlanzapine
Olanzapine will be administered in accordance with the label or Investigator's discretion
DRUGOral Paliperidone ER
Paliperidone Extended Release (ER) tablets 1.5 to 12 milligram (mg) per day will be administered orally.
DRUGPerphenazine
Perphenazine will be administered in accordance with the label or Investigator's discretion
DRUGQuetiapine
Quetiapine will be administered in accordance with the label or Investigator's discretion
DRUGOral Risperidone
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.
DRUGPaliperidone 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.
Sponsors
Janssen Scientific Affairs, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part-2 (Disease Progression): Time to First Treatment Failure | From Day 1 up to 9 Months | 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. |
| Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Baseline and 18 Months | 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. |
| Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Baseline and Day 260 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain | Baseline and Day 260 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | Baseline, up to 9 Months of Part 2 | 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. |
| 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) | Baseline, up to 9 Months | 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. |
| Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score | Baseline and endpoint Part 2 (up to 9 Months) | 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. |
| Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | Baseline and 18 Months | 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. |
| 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) | Baseline and 18 Months | 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. |
| Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | Baseline and Month 9 | 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. |
| Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain | Baseline and 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | Baseline, up to 18 Months | 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. |
| Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Baseline, up to 18 Months | 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. |
| Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score | Baseline, up to 18 Months | 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. |
| Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score | Month 9 of Part 3 | 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. |
| 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) | Baseline and Month 9 of Part 3 | 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. |
| Part 3 (EDP): Time to First Treatment Failure | From Day 1 Up to 18 Months | 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. |
| Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | Baseline and Month 9 | 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. |
| Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI) | Baseline and Day 260 | 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. |
Countries
Brazil, Mexico, United States
Participant flow
Recruitment details
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.
Pre-assignment details
To ensure that the total number of participants equal 337, another group is created called Healthy Controls to the table below and their completion status is reported in Part 1 and not in other parts.
Participants by arm
| Arm | Count |
|---|---|
| Part 1-Oral Antipsychotics (OAP) All participants received paliperidone extended Release (ER) 1.5 to 12 milligrams (mg) or risperidone 1 to 6 mg once daily orally for 2 months. Participants who tolerated paliperidone ER/risperidone but found 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. | 273 |
| Total | 273 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Part 1: 2-Month Oral Run-in Phase | Adverse Event | 7 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: 2-Month Oral Run-in Phase | Does not Tolerate Paliperidone ER | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: 2-Month Oral Run-in Phase | Lost to Follow-up | 11 | 0 | 0 | 0 | 0 | 0 | 23 |
| Part 1: 2-Month Oral Run-in Phase | Other | 5 | 0 | 0 | 0 | 0 | 0 | 3 |
| Part 1: 2-Month Oral Run-in Phase | Withdrawal of Consent | 9 | 0 | 0 | 0 | 0 | 0 | 6 |
| Part 2: 9Month Disease Progression Phase | Adverse Event | 0 | 5 | 1 | 0 | 0 | 0 | 0 |
| Part 2: 9Month Disease Progression Phase | Assigned OAP, but required PP | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| Part 2: 9Month Disease Progression Phase | Assigned PP, but required OAP | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Part 2: 9Month Disease Progression Phase | Lost to Follow-up | 0 | 6 | 13 | 0 | 0 | 0 | 0 |
| Part 2: 9Month Disease Progression Phase | Other | 0 | 2 | 2 | 0 | 0 | 0 | 0 |
| Part 2: 9Month Disease Progression Phase | Withdrawal by Subject | 0 | 11 | 8 | 0 | 0 | 0 | 0 |
| Part 3: 9 Month of Additional Treatment | Adverse Event | 0 | 0 | 0 | 2 | 3 | 0 | 0 |
| Part 3: 9 Month of Additional Treatment | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 5 | 0 |
| Part 3: 9 Month of Additional Treatment | Other | 0 | 0 | 0 | 1 | 1 | 6 | 0 |
| Part 3: 9 Month of Additional Treatment | Withdrawal by Subject | 0 | 0 | 0 | 5 | 6 | 6 | 0 |
Baseline characteristics
| Characteristic | Part 1-Oral Antipsychotics (OAP) |
|---|---|
| Age, Continuous | 23.2 years STANDARD_DEVIATION 4.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 95 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 173 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 17 Participants |
| Race/Ethnicity, Customized Black or African American | 91 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Other | 39 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 124 Participants |
| Region of Enrollment BRAZIL | 40 Participants |
| Region of Enrollment MEXICO | 26 Participants |
| Region of Enrollment UNITED STATES | 207 Participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 273 | 1 / 78 | 0 / 157 | 0 / 49 | 0 / 57 | 0 / 63 |
| other Total, other adverse events | 116 / 273 | 50 / 78 | 89 / 157 | 18 / 49 | 34 / 57 | 27 / 63 |
| serious Total, serious adverse events | 10 / 273 | 10 / 78 | 19 / 157 | 1 / 49 | 3 / 57 | 8 / 63 |
Outcome results
Primary
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
Population: Part 2 Intent-to-Treat (ITT) analysis set included all randomized participants who received at least one dose of study medication (or any portion of the dose) in Part 2, regardless of their compliance with the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part-2 (Disease Progression): Time to First Treatment Failure | NA days |
| Part-2: OAP | Part-2 (Disease Progression): Time to First Treatment Failure | NA days |
Primary
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
Population: Part 3 ITT analysis set included all randomized participants who received at least one dose of study medication (or any portion of the dose) in Part 3, regardless of their compliance with the protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | -0.7 T-score | Standard Error 1.02 |
| Part-2: OAP | Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | -0.2 T-score | Standard Error 0.95 |
| 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 | 0.5 T-score | Standard Error 0.96 |
Primary
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
Population: Part 3 ITT analysis set included all randomized participants who received at least one dose of study medication (or any portion of the dose) in Part 3, regardless of their compliance with the protocol. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 1.6 T-score | Standard Error 1.19 |
| Part-2: OAP | Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 3.2 T-score | Standard Error 1.11 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | 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 ratio | Standard Error 0.002 |
| 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) | -0.004 ratio | Standard Error 0.001 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 3.2 T-score | Standard Error 1.18 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 0.7 T-score | Standard Error 0.85 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.2 units on a scale | Standard Deviation 1.06 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.3 units on a scale | Standard Deviation 0.94 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 2.0 T-score | Standard Error 1.01 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score | 2.8 T-score | Standard Error 0.73 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 2.5 units on a scale | Standard Error 1.6 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 2.9 units on a scale | Standard Error 1.13 |
Secondary
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)
Population: Analysis was performed on Part 2 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score | -0.2 units on a scale | Standard Deviation 1.44 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score | 0.1 units on a scale | Standard Deviation 1.16 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 0.2 T-score | Standard Error 1.16 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 2.8 T-score | Standard Error 0.83 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain | 0.3 T-score | Standard Error 1.25 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain | 1.6 T-score | Standard Error 0.89 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain | 1.8 T-score | Standard Error 1.21 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain | 3.5 T-score | Standard Error 0.87 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain | 1.3 T-score | Standard Error 1.22 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain | 1.0 T-score | Standard Error 0.85 |
Secondary
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
Population: Analysis was performed on part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain | 1.3 T-score | Standard Error 1.29 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain | 1.4 T-score | Standard Error 0.93 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain | -0.2 T-score | Standard Error 1.08 |
| Part-2: OAP | Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain | -0.8 T-score | Standard Error 0.77 |
Secondary
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
Population: Analysis was performed on Part 2 ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | 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) | Negative Symptoms | Unchanged | 16 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Delusions | Worsened | 10 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Negative Symptoms | Improved | 17 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Delusions | Improved | 17 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Impaired Cognition | Worsened | 13 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Abnormal Psychomotor Behavior | Worsened | 9 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Impaired Cognition | Unchanged | 22 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Hallucinations | Improved | 14 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Impaired Cognition | Improved | 15 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Abnormal Psychomotor Behavior | Unchanged | 37 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Mania | Worsened | 1 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Disorganized Speech | Worsened | 2 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Mania | Unchanged | 47 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Abnormal Psychomotor Behavior | Improved | 4 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Mania | Improved | 2 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Delusions | Unchanged | 23 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Depression | Worsened | 7 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Disorganized Speech | Improved | 12 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Depression | Unchanged | 33 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Negative Symptoms | Worsened | 17 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Depression | Improved | 10 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Hallucinations | Worsened | 7 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Disorganized Speech | Unchanged | 36 Participants |
| Part-2: Paliperidone Palmitate (PP) | 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) | Hallucinations | Unchanged | 29 Participants |
| Part-2: OAP | 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) | Depression | Worsened | 28 Participants |
| Part-2: OAP | 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) | Depression | Improved | 23 Participants |
| Part-2: OAP | 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) | Hallucinations | Unchanged | 73 Participants |
| Part-2: OAP | 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) | Hallucinations | Improved | 33 Participants |
| Part-2: OAP | 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) | Delusions | Worsened | 20 Participants |
| Part-2: OAP | 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) | Delusions | Unchanged | 70 Participants |
| Part-2: OAP | 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) | Delusions | Improved | 35 Participants |
| Part-2: OAP | 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) | Disorganized Speech | Worsened | 13 Participants |
| Part-2: OAP | 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) | Disorganized Speech | Unchanged | 85 Participants |
| Part-2: OAP | 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) | Disorganized Speech | Improved | 27 Participants |
| Part-2: OAP | 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) | Abnormal Psychomotor Behavior | Worsened | 14 Participants |
| Part-2: OAP | 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) | Abnormal Psychomotor Behavior | Unchanged | 86 Participants |
| Part-2: OAP | 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) | Abnormal Psychomotor Behavior | Improved | 25 Participants |
| Part-2: OAP | 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) | Negative Symptoms | Worsened | 25 Participants |
| Part-2: OAP | 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) | Negative Symptoms | Unchanged | 61 Participants |
| Part-2: OAP | 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) | Negative Symptoms | Improved | 39 Participants |
| Part-2: OAP | 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) | Impaired Cognition | Worsened | 29 Participants |
| Part-2: OAP | 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) | Impaired Cognition | Unchanged | 52 Participants |
| Part-2: OAP | 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) | Impaired Cognition | Improved | 44 Participants |
| Part-2: OAP | 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) | Mania | Worsened | 7 Participants |
| Part-2: OAP | 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) | Mania | Unchanged | 107 Participants |
| Part-2: OAP | 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) | Mania | Improved | 11 Participants |
| Part-2: OAP | 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) | Depression | Unchanged | 74 Participants |
| Part-2: OAP | 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) | Hallucinations | Worsened | 19 Participants |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | 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 ratio | Standard Error 1.02 |
| Part-2: 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) | -0.2 ratio | Standard Error 0.95 |
| 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) | 0.5 ratio | Standard Error 0.96 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score | 67.6 units on a scale | Standard Error 1.81 |
| Part-2: OAP | Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score | 66.1 units on a scale | Standard Error 1.7 |
| Part 3-OAP to OAP | Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score | 66.6 units on a scale | Standard Error 1.7 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | 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 ratio | Standard Error 0.001 |
| Part-2: 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) | -0.003 ratio | Standard Error 0.001 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 2.4 T-score | Standard Error 1.46 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain | 0.7 T-score | Standard Error 1.35 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.7 units on a scale | Standard Deviation 0.14 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score | -0.7 units on a scale | Standard Deviation 0.14 |
Secondary
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
Population: Analysis was performed on part 3 ITT analysis set. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 7.5 units on a scale | Standard Error 1.94 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score | 7.0 units on a scale | Standard Error 1.82 |
Secondary
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
Population: Analysis was performed on part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score | 0.3 units on a scale | Standard Deviation 0.18 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score | 0.4 units on a scale | Standard Deviation 0.18 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 3.4 T-score | Standard Error 1.46 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain | 4.7 T-score | Standard Error 1.34 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain | -0.2 T-score | Standard Error 1.36 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain | 1.4 T-score | Standard Error 1.26 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain | 2.5 T-score | Standard Error 1.32 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain | 4.9 T-score | Standard Error 1.24 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain | 0.3 T-score | Standard Error 1.24 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain | 0.8 T-score | Standard Error 1.15 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain | 0.2 T-score | Standard Error 1.42 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain | -0.2 T-score | Standard Error 1.35 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain | -1.7 T-score | Standard Error 1.24 |
| Part-2: OAP | Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain | 0.7 T-score | Standard Error 1.16 |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set. Here, N (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Worsened | 2 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Unchanged | 27 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Improved | 11 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Worsened | 6 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Unchanged | 21 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Improved | 14 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Worsened | 3 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Unchanged | 27 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Improved | 12 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Worsened | 4 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Unchanged | 32 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Improved | 5 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Worsened | 11 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Unchanged | 11 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Improved | 19 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Worsened | 10 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Unchanged | 14 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Improved | 17 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Worsened | 0 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Unchanged | 40 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Improved | 1 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Worsened | 7 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Unchanged | 26 Participants |
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Improved | 8 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Unchanged | 29 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Worsened | 8 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Worsened | 4 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Unchanged | 29 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Worsened | 3 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Hallucinations | Improved | 10 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Unchanged | 22 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Worsened | 10 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Worsened | 6 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Unchanged | 20 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Negative Symptoms | Improved | 21 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Delusions | Improved | 17 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Unchanged | 39 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Worsened | 3 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Worsened | 9 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Unchanged | 36 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Depression | Improved | 12 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Disorganized Speech | Improved | 8 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Unchanged | 23 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Worsened | 2 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Mania | Improved | 5 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Unchanged | 37 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Impaired Cognition | Improved | 15 Participants |
| Part-2: OAP | Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS | Abnormal Psychomotor Behavior | Improved | 8 Participants |
Secondary
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
Population: Analysis was performed on Part 3 ITT analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part-2: Paliperidone Palmitate (PP) | Part 3 (EDP): Time to First Treatment Failure | NA days |
| Part-2: OAP | Part 3 (EDP): Time to First Treatment Failure | NA days |