Trial Outcomes & Findings for A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform (NCT NCT02431702)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

337 participants

Primary outcome timeframe

From Day 1 up to 9 Months

Results posted on

2025-04-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Part 1-Run-in: 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.	Part 2-Paliperidone Palmitate (PP) Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months.	Part 2-OAP Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) Participants who completed Part 2 and who were eligible based on matched criteria identified in Part 1 continued on the PP Treatment Group in Part 3. Participants continued to receive Paliperidone Palmitate for another 9 months (up to Day 260 Part 3).	Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive PP treatment for additional 9 months (up to Day 260). PP treatment includes PP1M or PP3M. Participants subsequently switched to PP3M following a minimum of 5 injections of PP1M.	Part 3-OAP to OAP (EDP and Disease Modification) Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).	Healthy Controls Participants did not receive any study medication and did not fall into any of the 3 parts of the study. For reporting purposes, the completion of the Healthy Controls were entered in Part 1 and not in the other parts.
Part 1: 2-Month Oral Run-in Phase STARTED	273	0	0	0	0	0	64
Part 1: 2-Month Oral Run-in Phase COMPLETED	239	0	0	0	0	0	32
Part 1: 2-Month Oral Run-in Phase NOT COMPLETED	34	0	0	0	0	0	32
Part 2: 9Month Disease Progression Phase STARTED	0	78	157	0	0	0	0
Part 2: 9Month Disease Progression Phase COMPLETED	0	52	128	0	0	0	0
Part 2: 9Month Disease Progression Phase NOT COMPLETED	0	26	29	0	0	0	0
Part 3: 9 Month of Additional Treatment STARTED	0	0	0	49	57	63	0
Part 3: 9 Month of Additional Treatment COMPLETED	0	0	0	40	47	46	0
Part 3: 9 Month of Additional Treatment NOT COMPLETED	0	0	0	9	10	17	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1-Run-in: 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.	Part 2-Paliperidone Palmitate (PP) Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months.	Part 2-OAP Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) Participants who completed Part 2 and who were eligible based on matched criteria identified in Part 1 continued on the PP Treatment Group in Part 3. Participants continued to receive Paliperidone Palmitate for another 9 months (up to Day 260 Part 3).	Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive PP treatment for additional 9 months (up to Day 260). PP treatment includes PP1M or PP3M. Participants subsequently switched to PP3M following a minimum of 5 injections of PP1M.	Part 3-OAP to OAP (EDP and Disease Modification) Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).	Healthy Controls Participants did not receive any study medication and did not fall into any of the 3 parts of the study. For reporting purposes, the completion of the Healthy Controls were entered in Part 1 and not in the other parts.
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 Lost to Follow-up	11	0	0	0	0	0	23
Part 1: 2-Month Oral Run-in Phase Withdrawal of Consent	9	0	0	0	0	0	6
Part 1: 2-Month Oral Run-in Phase Other	5	0	0	0	0	0	3
Part 1: 2-Month Oral Run-in Phase Does not Tolerate Paliperidone ER	2	0	0	0	0	0	0
Part 2: 9Month Disease Progression Phase Adverse Event	0	5	1	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 Withdrawal by Subject	0	11	8	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 Other	0	2	2	0	0	0	0
Part 2: 9Month Disease Progression Phase Assigned OAP, but required PP	0	0	5	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 Withdrawal by Subject	0	0	0	5	6	6	0
Part 3: 9 Month of Additional Treatment Other	0	0	0	1	1	6	0

Baseline Characteristics

A Study to Compare Disease Progression and Modification Following Treatment With Paliperidone Palmitate Long-Acting Injection or Oral Antipsychotics in Participant's With Recent-onset Schizophrenia or Schizophreniform

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1-Oral Antipsychotics (OAP) n=273 Participants 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.
Age, Continuous	23.2 years STANDARD_DEVIATION 4.38 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	213 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	95 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	173 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	91 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants
Race/Ethnicity, Customized White	124 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	39 Participants n=5 Participants
Region of Enrollment BRAZIL	40 Participants n=5 Participants
Region of Enrollment MEXICO	26 Participants n=5 Participants
Region of Enrollment UNITED STATES	207 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part-2 (Disease Progression): Time to First Treatment Failure	NA days Interval 263.0 to Here, NA signifies median or upper limit of CI was not estimable due to less than 50% of participants experienced an event..	NA days Here, NA signifies that median or upper/lower limit of CI was not estimable due to less than 50% of participants experienced an event.	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=39 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=44 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	3.2 T-score Standard Error 1.11	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=57 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP n=63 Participants Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	-0.2 T-score Standard Error 0.95	0.5 T-score Standard Error 0.96

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=52 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=118 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	2.8 T-score Standard Error 0.73	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=51 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=125 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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 1.60	2.9 units on a scale Standard Error 1.13	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=9 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=25 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	-0.004 ratio Standard Error 0.001	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain	-0.2 T-score Standard Error 1.08	-0.8 T-score Standard Error 0.77	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain	1.3 T-score Standard Error 1.22	1.0 T-score Standard Error 0.85	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain	1.8 T-score Standard Error 1.21	3.5 T-score Standard Error 0.87	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain	3.2 T-score Standard Error 1.18	0.7 T-score Standard Error 0.85	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain	1.3 T-score Standard Error 1.29	1.4 T-score Standard Error 0.93	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain	0.2 T-score Standard Error 1.16	2.8 T-score Standard Error 0.83	—

SECONDARY outcome

Timeframe: Baseline and Day 260

Population: Analysis was performed on Part 2 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=78 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=157 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain	0.3 T-score Standard Error 1.25	1.6 T-score Standard Error 0.89	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=52 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=126 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	-0.3 units on a scale Standard Deviation 0.94	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=50 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=125 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	70 Participants	—
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	35 Participants	—
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	13 Participants	—
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	85 Participants	—
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	27 Participants	—
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	14 Participants	—
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	86 Participants	—
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	25 Participants	—
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	25 Participants	—
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	61 Participants	—
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	39 Participants	—
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	29 Participants	—
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	52 Participants	—
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	44 Participants	—
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	107 Participants	—
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	7 Participants	—
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	11 Participants	—
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	28 Participants	—
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	74 Participants	—
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	23 Participants	—
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	19 Participants	—
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	73 Participants	—
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	33 Participants	—
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	20 Participants	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=73 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=156 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score	-0.2 units on a scale Standard Deviation 1.44	0.1 units on a scale Standard Deviation 1.16	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=41 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=47 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	7.0 units on a scale Standard Error 1.82	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
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	-0.003 ratio Standard Error 0.001	—

SECONDARY outcome

Timeframe: From Day 1 Up to 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Time to First Treatment Failure	NA days Here, NA signifies that median and upper/lower limit of CI was not estimable due to less number of events.	NA days Interval 376.0 to Here, NA signifies that median and upper/lower limit of CI was not estimable due to less number of events.	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain	-1.7 T-score Standard Error 1.24	0.7 T-score Standard Error 1.16	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain	0.3 T-score Standard Error 1.24	0.8 T-score Standard Error 1.15	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain	2.5 T-score Standard Error 1.32	4.9 T-score Standard Error 1.24	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain	2.4 T-score Standard Error 1.46	0.7 T-score Standard Error 1.35	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain	0.2 T-score Standard Error 1.42	-0.2 T-score Standard Error 1.35	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain	3.4 T-score Standard Error 1.46	4.7 T-score Standard Error 1.34	—

SECONDARY outcome

Timeframe: Baseline and 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain	-0.2 T-score Standard Error 1.36	1.4 T-score Standard Error 1.26	—

SECONDARY outcome

Timeframe: Baseline, up to 18 Months

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score	-0.7 units on a scale Standard Deviation 0.14	-0.7 units on a scale Standard Deviation 0.14	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=41 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=47 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Hallucinations · Worsened	3 Participants	8 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Hallucinations · Unchanged	27 Participants	29 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Hallucinations · Improved	11 Participants	10 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Delusions · Worsened	6 Participants	10 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Delusions · Unchanged	21 Participants	20 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Delusions · Improved	14 Participants	17 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Disorganized Speech · Worsened	2 Participants	3 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Disorganized Speech · Unchanged	27 Participants	36 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Disorganized Speech · Improved	12 Participants	8 Participants	—
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	2 Participants	—
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	37 Participants	—
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	8 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Negative Symptoms · Worsened	11 Participants	4 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Negative Symptoms · Unchanged	11 Participants	22 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Negative Symptoms · Improved	19 Participants	21 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Impaired Cognition · Worsened	10 Participants	9 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Impaired Cognition · Unchanged	14 Participants	23 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Impaired Cognition · Improved	17 Participants	15 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Mania · Worsened	0 Participants	3 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Mania · Unchanged	40 Participants	39 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Mania · Improved	1 Participants	5 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Depression · Worsened	7 Participants	6 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Depression · Unchanged	26 Participants	29 Participants	—
Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS Depression · Improved	8 Participants	12 Participants	—

SECONDARY outcome

Timeframe: Baseline, up to 18 Months

Population: Analysis was performed on part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=63 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score	0.3 units on a scale Standard Deviation 0.18	0.4 units on a scale Standard Deviation 0.18	—

SECONDARY outcome

Timeframe: Month 9 of Part 3

Population: Analysis was performed on Part 3 ITT analysis set.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=49 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=57 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP n=63 Participants Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score	67.6 units on a scale Standard Error 1.81	66.1 units on a scale Standard Error 1.70	66.6 units on a scale Standard Error 1.70

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part-2: Paliperidone Palmitate (PP) n=10 Participants Participants who completed part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months. Participants were subsequently switched to PP3M (paliperidone palmitate three-monthly injection) following a minimum of 5 injections of PP1M.	Part-2: OAP n=8 Participants Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were re-randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-OAP to OAP n=9 Participants Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)	-0.7 ratio Standard Error 1.02	-0.2 ratio Standard Error 0.95	0.5 ratio Standard Error 0.96

Adverse Events

Part 1-Run-in: Oral Antipsychotics (OAP)

Serious events: 10 serious events

Other events: 116 other events

Deaths: 0 deaths

Part 2-Paliperidone Palmitate (PP)

Serious events: 10 serious events

Other events: 50 other events

Deaths: 1 deaths

Part 2-OAP

Serious events: 19 serious events

Other events: 89 other events

Deaths: 0 deaths

Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification)

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification)

Serious events: 3 serious events

Other events: 34 other events

Deaths: 0 deaths

Part 3-OAP to OAP (EDP and Disease Modification)

Serious events: 8 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part 1-Run-in: Oral Antipsychotics (OAP) n=273 participants at risk 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.	Part 2-Paliperidone Palmitate (PP) n=78 participants at risk Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months.	Part 2-OAP n=157 participants at risk Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) n=49 participants at risk Participants who completed Part 2 and who were eligible based on matched criteria identified in Part 1 continued on the PP Treatment Group in Part 3. Participants continued to receive Paliperidone Palmitate for another 9 months (up to Day 260 Part 3).	Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) n=57 participants at risk Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive PP treatment for additional 9 months (up to Day 260). PP treatment includes PP1M or PP3M. Participants subsequently switched to PP3M following a minimum of 5 injections of PP1M.	Part 3-OAP to OAP (EDP and Disease Modification) n=63 participants at risk Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
General disorders Asthenia	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Injury, poisoning and procedural complications Exposure Via Inhalation	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Injury, poisoning and procedural complications Overdose	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.64% 1/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ganglioglioma	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Agitation	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Catatonia	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Completed Suicide	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.8% 1/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Depressed Mood	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Homicidal Ideation	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Mania	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Mental Status Changes	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.64% 1/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Psychotic Disorder	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 4/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.2% 5/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.3% 4/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Psychotic Symptom	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.9% 3/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.2% 2/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Schizophrenia	1.1% 3/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.8% 3/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.8% 6/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Suicidal Ideation	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.8% 3/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.5% 4/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.5% 2/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Suicide Attempt	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Cardiac disorders Tachycardia	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Infections and infestations Appendicitis	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.

Other adverse events

Other adverse events
Measure	Part 1-Run-in: Oral Antipsychotics (OAP) n=273 participants at risk 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.	Part 2-Paliperidone Palmitate (PP) n=78 participants at risk Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who were randomized to the PP treatment group received a minimum of 5 doses of PP1M with fixed initial doses of 234 mg on Day 1 and 156 mg on Day 8, followed by 3 injections of flexible doses. On Day 120, participants received PP3M for the remaining 9 months.	Part 2-OAP n=157 participants at risk Participants who completed Part 1 with acceptable run-in dosages were eligible to enter Part 2. Participants who completed Part 1 were randomized to OAP treatment group and continued their OAP treatment from Part 1 for another 9 months (up to Day 260 of Part 2).	Part 3-PP to PP (Extended Disease Progression [EDP] and Disease Modification) n=49 participants at risk Participants who completed Part 2 and who were eligible based on matched criteria identified in Part 1 continued on the PP Treatment Group in Part 3. Participants continued to receive Paliperidone Palmitate for another 9 months (up to Day 260 Part 3).	Part 3- OAP to PP (or Delayed-Start PP) (Disease Modification) n=57 participants at risk Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive PP treatment for additional 9 months (up to Day 260). PP treatment includes PP1M or PP3M. Participants subsequently switched to PP3M following a minimum of 5 injections of PP1M.	Part 3-OAP to OAP (EDP and Disease Modification) n=63 participants at risk Participants who completed Part 2 (with OAP treatment) and who were eligible based on matched criteria identified in Part 1 were re-randomized to receive OAP treatment for another 9 months (up to Day 260 of Part 3).
Gastrointestinal disorders Nausea	1.8% 5/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 4/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.0% 11/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	4.1% 2/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.5% 2/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.9% 5/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
General disorders Fatigue	3.7% 10/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 4/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.64% 1/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	8.8% 5/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
General disorders Injection Site Pain	1.5% 4/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.7% 6/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 2/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Infections and infestations Nasopharyngitis	0.37% 1/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.4% 5/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.5% 4/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.1% 3/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.3% 4/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Infections and infestations Upper Respiratory Tract Infection	2.2% 6/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	4.5% 7/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.3% 3/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.2% 2/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Investigations Blood Prolactin Increased	2.9% 8/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.8% 3/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.7% 9/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Investigations Weight Increased	16.1% 44/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	28.2% 22/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	31.8% 50/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	14.3% 7/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	15.8% 9/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.9% 5/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Musculoskeletal and connective tissue disorders Musculoskeletal Stiffness	0.73% 2/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 4/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.9% 3/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.8% 1/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.2% 2/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Nervous system disorders Akathisia	3.7% 10/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	9.0% 7/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 8/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.0% 4/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Nervous system disorders Headache	4.0% 11/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	9.0% 7/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	7.6% 12/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.5% 2/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.3% 4/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Nervous system disorders Sedation	5.9% 16/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.8% 3/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.9% 3/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.5% 2/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Nervous system disorders Somnolence	7.0% 19/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	9.0% 7/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.5% 4/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.3% 3/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Nervous system disorders Tremor	2.2% 6/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	4.5% 7/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	4.1% 2/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	8.8% 5/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	3.2% 2/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Anxiety	1.8% 5/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.4% 5/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.5% 4/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	10.5% 6/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	4.8% 3/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Insomnia	3.3% 9/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.1% 4/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.7% 9/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	10.2% 5/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	10.5% 6/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.3% 4/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Paranoia	0.00% 0/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	6.1% 3/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	0.00% 0/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.
Psychiatric disorders Schizophrenia	1.1% 3/273 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.3% 1/78 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.5% 4/157 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	2.0% 1/49 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	5.3% 3/57 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.	1.6% 1/63 • Up to 20 Months Safety analysis was based on Part 1, 2 and 3 Intent-to-Treat (ITT) analysis set. Part 1, 2 and 3 ITT analysis set included all randomized subjects who received at least one dose of study medication (or any portion of the dose) in Part 1, 2 and 3 regardless of their compliance with the protocol.

Additional Information

Senior Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER