Trial Outcomes & Findings for Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Patients With Schizophrenia (NCT NCT01515423)

Last Updated: 2016-05-02

Results Overview

Relapse defined as: Psychiatric hospitalization;participant had an increase of 25 percent in total PANSS score from randomization for 2 consecutive assessments separated by 3-7 days if score at randomization was greater than (\>) 40; had a 10 point increase in total PANSS score from randomization for 2 consecutive assessments separated by 3-7 days if score at randomization was less than or equal to (\<=) 40; deliberate self-injury or exhibited violent behavior resulting in suicide, clinically significant injury;suicidal or homicidal ideation and aggressive behavior;For PANSS items-had a score of greater than or equal to (\>=) 5 after randomization for 2 consecutive assessments separated by 3-7 days on any of above items if maximum score for these above PANSS items was \<=3 at randomization; had a score of \>=6 after randomization for 2 consecutive assessments separated by 3-7 days on any of above items if maximum score for these above PANSS items was 4 at randomization.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1429 participants

Primary outcome timeframe

Up to 48 weeks

Results posted on

2016-05-02

Participant Flow

1429 participants received at least 1 dose of the study agent in the Open-label Phase, out of which 1016 participants were randomized into the Double blind Phase (Safety population).

Participant milestones

Participant milestones
Measure	Open-Label: Paliperidone Palmitate (PP1M) 1-month Formulation Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a dose of 150 milligram equivalent (mg eq.) on Day 1 and 100 mg eq. on Day 8, both as an injection in the deltoid muscle. The injections at Week 5 (Day 36) and Week 9 (Day 64) given in either the deltoid or gluteal muscle and were flexibly dosed (50, 75, 100, or 150 mg eq.). At Week 13 (Day 92) participants received the same dose of PP1M that was administered at Week 9.	Double-Blind: Paliperidone Palmitate(PP3M) 3-month Formulation Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double-Blind: Paliperidone Palmitate(PP1M) 1-month Formulation Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Open Label Phase STARTED	1429	0	0
Open Label Phase COMPLETED	1016	0	0
Open Label Phase NOT COMPLETED	413	0	0
DOUBLE BLIND STARTED	0	504	512
DOUBLE BLIND COMPLETED	0	422	420
DOUBLE BLIND NOT COMPLETED	0	82	92

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-Label: Paliperidone Palmitate (PP1M) 1-month Formulation Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a dose of 150 milligram equivalent (mg eq.) on Day 1 and 100 mg eq. on Day 8, both as an injection in the deltoid muscle. The injections at Week 5 (Day 36) and Week 9 (Day 64) given in either the deltoid or gluteal muscle and were flexibly dosed (50, 75, 100, or 150 mg eq.). At Week 13 (Day 92) participants received the same dose of PP1M that was administered at Week 9.	Double-Blind: Paliperidone Palmitate(PP3M) 3-month Formulation Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double-Blind: Paliperidone Palmitate(PP1M) 1-month Formulation Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Open Label Phase Adverse Event	57	0	0
Open Label Phase Death	2	0	0
Open Label Phase Lack of Efficacy	117	0	0
Open Label Phase Lost to Follow-up	21	0	0
Open Label Phase Withdrawal by Subject	118	0	0
Open Label Phase excluded from DB Phase	70	0	0
Open Label Phase Other	28	0	0
DOUBLE BLIND Adverse Event	0	15	13
DOUBLE BLIND Death	0	1	2
DOUBLE BLIND Lost to Follow-up	0	7	12
DOUBLE BLIND Pregnancy	0	2	0
DOUBLE BLIND Withdrawal by Subject	0	50	53
DOUBLE BLIND Other	0	6	12
DOUBLE BLIND Blind broken by investigator	0	1	0

Baseline Characteristics

Study of Paliperidone Palmitate 3 Month and 1 Month Formulations for the Treatment of Patients With Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-Blind: Paliperidone Palmitate(PP3M) 3-month Formulation n=504 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double-Blind: Paliperidone Palmitate(PP1M) 1-month Formulation n=512 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.	Total n=1016 Participants Total of all reporting groups
Age, Continuous	39.0 years STANDARD_DEVIATION 11.89 • n=5 Participants	38.3 years STANDARD_DEVIATION 12.24 • n=7 Participants	38.6 years STANDARD_DEVIATION 12.06 • n=5 Participants
Sex: Female, Male Female	246 Participants n=5 Participants	231 Participants n=7 Participants	477 Participants n=5 Participants
Sex: Female, Male Male	258 Participants n=5 Participants	281 Participants n=7 Participants	539 Participants n=5 Participants
Region of Enrollment China	104 participants n=5 Participants	106 participants n=7 Participants	210 participants n=5 Participants
Region of Enrollment Russian Federation	75 participants n=5 Participants	75 participants n=7 Participants	150 participants n=5 Participants
Region of Enrollment Japan	52 participants n=5 Participants	56 participants n=7 Participants	108 participants n=5 Participants
Region of Enrollment United States	41 participants n=5 Participants	48 participants n=7 Participants	89 participants n=5 Participants
Region of Enrollment Ukraine	35 participants n=5 Participants	29 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Czech Republic	31 participants n=5 Participants	29 participants n=7 Participants	60 participants n=5 Participants
Region of Enrollment Hungary	21 participants n=5 Participants	19 participants n=7 Participants	40 participants n=5 Participants
Region of Enrollment Poland	17 participants n=5 Participants	20 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Argentina	14 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Bulgaria	12 participants n=5 Participants	16 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment Brazil	13 participants n=5 Participants	12 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Spain	11 participants n=5 Participants	14 participants n=7 Participants	25 participants n=5 Participants
Region of Enrollment Slovakia	12 participants n=5 Participants	10 participants n=7 Participants	22 participants n=5 Participants
Region of Enrollment Portugal	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment Mexico	7 participants n=5 Participants	9 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Taiwan	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Region of Enrollment Romania	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Germany	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment South Korea	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Belgium	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Greece	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Australia	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment France	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Austria	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 48 weeks

Population: Modified intent-to-treat (mITT) analysis set included all participants who were randomly assigned to treatment during Double-blind Phase, received at least 1 dose of study drug and did not have any errors in delivery of active treatment. Here,N=number of participants analysed is the total participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Double Blind: Paliperidone Palmitate 3 Month Formulation n=458 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=490 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Percentage of Participants Without Relapse at Week 48 During the Double-Blind Phase	91.5 Percentage of Participants	90.0 Percentage of Participants

SECONDARY outcome

Timeframe: DB Baseline (Week 17) and 48 week or DB Endpoint

Population: mITT analysis set included all participants who were randomly assigned to treatment during Double-blind Phase, received at least 1 dose of study drug and did not have any errors in the delivery of active treatment. Here,N=number of participants analysed is the total participants who were evaluable for this outcome measure.

The neuropsychiatric symptoms of schizophrenia were assessed by means of the 30-item Positive and Negative Syndrome Scale (PANSS). The PANSS provides a total score (sum of the scores of all 30 items) ranging from 30 to 210, higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology).

Outcome measures

Outcome measures
Measure	Double Blind: Paliperidone Palmitate 3 Month Formulation n=481 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=503 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Change From Double-Blind (DB) Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 48 Change from Baseline at DB End point	-3.5 Units on a scale Standard Deviation 12.50	-4.3 Units on a scale Standard Deviation 11.78
Change From Double-Blind (DB) Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 48 Baseline	57.4 Units on a scale Standard Deviation 8.56	58.1 Units on a scale Standard Deviation 8.88

SECONDARY outcome

Timeframe: DB Baseline (Week 17) and 48 week or DB Endpoint

The Clinical Global Impression Severity (CGI-S) rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 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	Double Blind: Paliperidone Palmitate 3 Month Formulation n=481 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=504 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Change From DB Baseline in Clinical Global Impression Severity (CGI-S) Scale Score at Week 48 Baseline	2.9 Units on a scale Standard Deviation 0.57	2.9 Units on a scale Standard Deviation 0.66
Change From DB Baseline in Clinical Global Impression Severity (CGI-S) Scale Score at Week 48 Change from Baseline at DB End point	-0.1 Units on a scale Standard Deviation 0.84	-0.1 Units on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: DB Baseline (Week 17) and 48 week or DB Endpoint

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Score ranges from 1 to 100. Participants with a 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	Double Blind: Paliperidone Palmitate 3 Month Formulation n=474 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=495 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Change From DB Baseline in Personal and Social Performance (PSP) Total Score at Week 48 Baseline	65.5 Units on a scale Standard Deviation 10.40	65.0 Units on a scale Standard Deviation 11.06
Change From DB Baseline in Personal and Social Performance (PSP) Total Score at Week 48 Change from Baseline at DB End point	1.3 Units on a scale Standard Deviation 10.22	1.9 Units on a scale Standard Deviation 9.21

SECONDARY outcome

Timeframe: Weeks 41 to 65

Symptomatic remission criterion was defined as having a simultaneous score of mild or less on all selected PANSS items (P1, P2, P3, N1, N4, N6, G5, and G9). Symptomatic remission was defined for the last 6 months of the Double-blind Phase as meeting the remission criterion during the 6 months prior to the End of study visit during the Double-blind Phase, with one excursion allowed.

Outcome measures

Outcome measures
Measure	Double Blind: Paliperidone Palmitate 3 Month Formulation n=483 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=512 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Percentage of Participants Who Met the Criteria for Symptomatic Remission Based on Andreasen Criteria	58.4 Percentage of Participants Interval 0.89 to 1.08	59.2 Percentage of Participants Interval 0.89 to 1.08

SECONDARY outcome

Timeframe: DB Baseline (Week 17) and 48 week or DB Endpoint

Outcome measures

Outcome measures
Measure	Double Blind: Paliperidone Palmitate 3 Month Formulation n=483 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=512 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 Positive subscale: Baseline	11.9 Units on a scale Standard Deviation 3.12	12.0 Units on a scale Standard Deviation 3.19
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 Positive subscale:Change at Endpoint	-0.6 Units on a scale Standard Deviation 4.31	-0.9 Units on a scale Standard Deviation 3.70
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 Negative subscale: Baseline	17.3 Units on a scale Standard Deviation 4.27	17.3 Units on a scale Standard Deviation 4.11
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 Negative subscale:Change at Endpoint	-1.4 Units on a scale Standard Deviation 3.63	-1.4 Units on a scale Standard Deviation 3.67
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 General psychopathology : Baseline	28.2 Units on a scale Standard Deviation 4.55	28.8 Units on a scale Standard Deviation 4.79
Change From Baseline in Positive and Negative Syndrome Subscales Score at Week 48 General psychopathology : Change at Endpoint	-1.4 Units on a scale Standard Deviation 6.77	-2.0 Units on a scale Standard Deviation 6.57

SECONDARY outcome

Timeframe: DB Baseline (Week 17) and 48 week or DB Endpoint

5 PANSS Marder factor scores (positive symptoms \[range:8 to 56\], negative symptoms \[range: 7 to 49\], disorganized thoughts \[range: 7 to 49\], uncontrolled hostility/excitement \[range: 4 to 28\], and anxiety/depression \[range: 4 to 28\]) were examined to gain insight into the symptoms affected by treatment with the study drug. Negative change from baseline in subscales score for positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression indicates improvement in various symptoms of schizophrenia.

Outcome measures

Outcome measures
Measure	Double Blind: Paliperidone Palmitate 3 Month Formulation n=483 Participants Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double Blind: Paliperidone Palmitate 1 Month Formulation n=512 Participants Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
Change From Baseline in Marder Factor Subscale Score at Week 48 Positive symptoms factor: Baseline	15.7 Units on a scale Standard Deviation 3.66	15.8 Units on a scale Standard Deviation 3.88
Change From Baseline in Marder Factor Subscale Score at Week 48 Positive symptoms factor:Change at Endpoint	-1.1 Units on a scale Standard Deviation 4.61	-1.4 Units on a scale Standard Deviation 4.16
Change From Baseline in Marder Factor Subscale Score at Week 48 Negative symptoms factor: Baseline	16.2 Units on a scale Standard Deviation 4.03	16.3 Units on a scale Standard Deviation 3.90
Change From Baseline in Marder Factor Subscale Score at Week 48 Negative symptoms factor : Change at Endpoint	-1.4 Units on a scale Standard Deviation 3.57	-1.3 Units on a scale Standard Deviation 3.80
Change From Baseline in Marder Factor Subscale Score at Week 48 Disorganized thoughts factor :Baseline	14.2 Units on a scale Standard Deviation 3.20	14.3 Units on a scale Standard Deviation 3.17
Change From Baseline in Marder Factor Subscale Score at Week 48 Disorganized thoughts factor:Change at Endpoint	-1.2 Units on a scale Standard Deviation 3.36	-1.2 Units on a scale Standard Deviation 3.24
Change From Baseline in Marder Factor Subscale Score at Week 48 Uncontrolled hostility Factor:Baseline	5.2 Units on a scale Standard Deviation 1.64	5.4 Units on a scale Standard Deviation 1.77
Change From Baseline in Marder Factor Subscale Score at Week 48 Uncontrolled hostility Factor:Change at Endpoint	0.2 Units on a scale Standard Deviation 2.31	-0.2 Units on a scale Standard Deviation 2.21
Change From Baseline in Marder Factor Subscale Score at Week 48 Anxiety/depression factor:Baseline	6.1 Units on a scale Standard Deviation 2.02	6.3 Units on a scale Standard Deviation 2.12
Change From Baseline in Marder Factor Subscale Score at Week 48 Anxiety/depression factor:Change at Endpoint	-0.0 Units on a scale Standard Deviation 2.69	-0.2 Units on a scale Standard Deviation 2.43

Adverse Events

Open-Label: Paliperidone Palmitate (PP1M) 1-month Formulation

Serious events: 101 serious events

Other events: 457 other events

Deaths: 0 deaths

Double-Blind: Paliperidone Palmitate(PP3M) 3-month Formulation

Serious events: 26 serious events

Other events: 212 other events

Deaths: 0 deaths

Double-Blind: Paliperidone Palmitate(PP1M) 1-month Formulation

Serious events: 37 serious events

Other events: 208 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Open-Label: Paliperidone Palmitate (PP1M) 1-month Formulation n=1429 participants at risk Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a dose of 150 milligram equivalent (mg eq.) on Day 1 and 100 mg eq. on Day 8, both as an injection in the deltoid muscle. The injections at Week 5 (Day 36) and Week 9 (Day 64) given in either the deltoid or gluteal muscle and were flexibly dosed (50, 75, 100, or 150 mg eq.). At Week 13 (Day 92) participants received the same dose of PP1M that was administered at Week 9.	Double-Blind: Paliperidone Palmitate(PP3M) 3-month Formulation n=504 participants at risk Participants received Paliperidone Palmitate 3-month formulation (PP3M) in a fixed dose of 3.5 fold multiple of the PP1M dose administered at Week 13, that is participants received fixed dose injections of PP3M (175, 263, 350, or 525 mg eq.) on Week 17, 29, 41, and 53 as injection in deltoid muscle or gluteal muscle.	Double-Blind: Paliperidone Palmitate(PP1M) 1-month Formulation n=512 participants at risk Participants received Paliperidone Palmitate 1-month formulation (PP1M) in a fixed dose that was administered at Week 9 at every month for 48 weeks, that is, participants received fixed dose injections of PP1M (50, 75, 100, or 150 mg eq.) as injection on deltoid muscle or gluteal muscle.
General disorders Injection Site Induration	2.8% 40/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.8% 14/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	1.2% 6/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
General disorders Injection Site Pain	8.9% 127/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.4% 12/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.7% 14/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Infections and infestations Nasopharyngitis	4.6% 66/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	7.1% 36/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	6.4% 33/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Investigations Weight Decreased	0.70% 10/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.8% 14/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.7% 14/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Investigations Weight Increased	4.5% 64/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	20.8% 105/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	21.3% 109/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Nervous system disorders Akathisia	5.5% 78/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	4.0% 20/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.7% 14/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Nervous system disorders Headache	3.2% 46/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	3.6% 18/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	5.1% 26/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Psychiatric disorders Anxiety	5.5% 79/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	5.4% 27/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	4.3% 22/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Psychiatric disorders Insomnia	6.6% 94/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	3.2% 16/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	4.7% 24/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.
Vascular disorders Hypertension	0.77% 11/1429 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	2.4% 12/504 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.	1.4% 7/512 • From signing of informed consent form up to Follow-Up Visit (4 or 12 Weeks after study drug administration) For Double-blind (DB) phase, safety analysis set included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study drug. For Open-label Phase, all participants who received at least 1 dose of open-label study drug and were included in summary of safety assessments for that phase.

Additional Information

Director Clinical Research

Janssen Research & Development, LLC

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER