Trial Outcomes & Findings for Evaluation of Effectiveness and Safety of Flexible-dose Paliperidone Extended Release in Patients With Schizoaffective Disorder. (NCT NCT00412373)

NCT ID: NCT00412373

Last Updated: 2014-05-09

Results Overview

The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 307 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2014-05-09

Participant Flow

391 subjects were enrolled in the study. There were 80 screen fails (did not meet inclusion/exclusion criteria). 311 subjects were randomized. 309 subjects were included in the Safety Analysis Set (randomized and took at least one dose of study drug). 304 subjects were included in the Intent-to-Treat analysis set (had baseline/postbase PANSS).

Participant milestones

Measure	Placebo A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Overall Study STARTED	93	211
Overall Study COMPLETED	52	134
Overall Study NOT COMPLETED	41	77

Reasons for withdrawal

Measure	Placebo A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Overall Study Adverse Event	8	13
Overall Study Lack of Efficacy	16	22
Overall Study Lost to Follow-up	7	13
Overall Study Withdrawal by Subject	8	27
Overall Study Other	2	2

Baseline Characteristics

Evaluation of Effectiveness and Safety of Flexible-dose Paliperidone Extended Release in Patients With Schizoaffective Disorder.

Baseline characteristics by cohort

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).	Total n=304 Participants Total of all reporting groups
Age, Continuous	37.3 years STANDARD_DEVIATION 9.4 • n=5 Participants	37.7 years STANDARD_DEVIATION 9.1 • n=7 Participants	37.6 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	95 Participants n=7 Participants	134 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	116 Participants n=7 Participants	170 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	29 Participants n=5 Participants	61 Participants n=7 Participants	90 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	38 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants	109 Participants n=7 Participants	156 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Population: The Intent-to-Treat population included all randomly assigned subjects who received at least 1 dose of study medication (or any portion of a dose) and had both baseline and at least 1 postbaseline PANSS assessment.

The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline.	91.7 points on a scale Standard Deviation 12.1	92.3 points on a scale Standard Deviation 13.5

PRIMARY outcome

Timeframe: The primary efficacy endpoint was the change from baseline to week 6 or the last post-randomization assessment during double-blind treatment in the PANSS total score.

Population: The Intent-to-Treat population included all randomly assigned subjects who received at least 1 dose of study medication (or any portion of a dose) and had both baseline and at least 1 postbaseline PANSS assessment.

The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-10.8 points on a scale Standard Deviation 18.7	-20.0 points on a scale Standard Deviation 18.9

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Positive Syndrome Scale (range 7-49): Sum of scores for items 1-7 in positive subscale: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-4.6 points on a scale Standard Deviation 6.3	-7.3 points on a scale Standard Deviation 6.9

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Negative Syndrome Scale (range 7-49): Sum of scores for items 1-7 in negative subscale: blunted effect, emotional withdrawal, poor rapport, passive apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-1.1 points on a scale Standard Deviation 5.5	-3.0 points on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

General Psychopathology (range 16-112): Sum of scores for somatic concern, anxiety, guilt feelings, tension, mannerisms/posturing, depression, motor retardation, uncooperativeness, unusual thought content, disoriented, poor attention, lack of judgment/insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-5.2 points on a scale Standard Deviation 9.4	-9.7 points on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Positive PANSS Factor Score (range 8-56): Sum of scores for items 1, 3, 5, and 6 in positive subscale: delusions, hallucinatory behavior, grandiosity, suspiciousness; item 7 in negative subscale: stereotyped thinking; and items 1, 9, and 12 in general psychopathology subscale: somatic concern, unusual thought content, lack of judgment, and insight. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-3.3 points on a scale Standard Deviation 5.8	-6.0 points on a scale Standard Deviation 6.9

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Negative PANSS Factor Score (range 7-49): Sum of scores for items 1, 2, 3, 4, and 6 in negative subscale: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity; and items 7 and 16 in general psychopathology subscale: motor retardation, and active social avoidance. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-1.1 points on a scale Standard Deviation 5.7	-3.1 points on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Disorganized Thoughts PANSS Factor Score (range 7-49): Sum of scores for item 2 in positive subscale:Conceptual disorganization; item 5 in negative subscale:difficulty in abstract thinking; and items 5, 10, 11, 13, and 15 in general psychopathology subscale: mannerisms/posturing, disorientation, poor attention, disturbance of volition, and preoccupation. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-1.4 points on a scale Standard Deviation 4.3	-3.3 points on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Uncontrolled Hostility/Excitement PANSS Factor Score (range 4-28): Sum of scores for items 4 and 7 in positive subscale: excitement, hostility; and items 8 and 14 in general psychopathology subscale: uncooperativeness, and poor impulse control. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-2.7 points on a scale Standard Deviation 4.2	-4.3 points on a scale Standard Deviation 4.4

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Anxiety/Depression PANSS Factor Score (range 4-28): Sum of scores for items 2, 3, 4, and 6 in general psychopathology subscale: Anxiety, Guilt feelings, Tension, Depression. Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-2.3 points on a scale Standard Deviation 3.6	-3.3 points on a scale Standard Deviation 3.7

SECONDARY outcome

Timeframe: Baseline

Population: Intent-to-Treat

The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. 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 subjects". Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline	4.6 points on a scale Standard Deviation 0.6	4.6 points on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. 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 subjects". Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-0.7 points on a scale Standard Deviation 1.2	-1.2 points on a scale Standard Deviation 1.2

SECONDARY outcome

Timeframe: Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

The CGI-C rating scale is a 7 point global assessment that measures the clinician's impression of the change occurring in the illness over a course of treatment, relative to baseline. A rating of 4 is equivalent to "No change". Ratings of <4 are equivalent to "improvement" and ratings of > 4 are equivalent to "worsening". Higher scores indicate worsening.

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder	3.4 points on a scale Standard Deviation 1.5	2.8 points on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Week 6 LOCF End Point

Population: Intent-to-Treat

Response is defined as a 30% or more reduction from baseline PANSS total score and CGI-C score of <= 2 (CGI-C-SCA: Clinical Global Impression of Change for Schizoaffective Disorder).

Outcome measures

Measure	Placebo n=93 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=211 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Participants With Response	26 participants	85 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: Intent-to-Treat

Clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on either a 5-point (0 to 4) or a 3-point (0 to 2) scale. The 5-point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. The responses are summed to yield the HAM-D-21 score that ranges from 0-63.

Outcome measures

Measure	Placebo n=65 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=145 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Baseline Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16	24.6 points on a scale Standard Deviation 5.3	24.6 points on a scale Standard Deviation 6.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

Clinician-rated scale that evaluates depressed mood as well as the vegetative and cognitive symptoms of depression. The items are rated on either a 5-point (0 to 4) or a 3-point (0 to 2) scale. The 5-point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. The responses are summed to yield the HAM-D-21 score that ranges from 0-63.

Outcome measures

Measure	Placebo n=65 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=145 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-6.2 points on a scale Standard Deviation 8.6	-10.2 points on a scale Standard Deviation 8.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: Intent-to-Treat

11-item scale (elevated mood, increased motor activity, sexual interest, sleep, irritability, speech [rate/amount], language-thought disorder, content, disruptive-aggressive behaviors, appearance, and insight) based on subject's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. The responses are summed to yield the YMRS total score, which ranges from 0 to 60.

Outcome measures

Measure	Placebo n=70 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=161 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16	26.9 points on a scale Standard Deviation 8.1	27.5 points on a scale Standard Deviation 7.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment

Population: Intent-to-Treat

11-item scale (elevated mood, increased motor activity, sexual interest, sleep, irritability, speech [rate/amount], language-thought disorder, content, disruptive-aggressive behaviors, appearance, and insight) based on subject's report of his or her condition and clinician's behavioral observations during the interview, with emphasis on the latter. Higher scores indicate worsening. The responses are summed to yield the YMRS total score, which ranges from 0 to 60.

Outcome measures

Measure	Placebo n=70 Participants A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=161 Participants Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.	-5.7 points on a scale Standard Deviation 10.0	-10.6 points on a scale Standard Deviation 10.8

Adverse Events

Placebo

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Paliperidone Extended-Release (ER)

Serious events: 11 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=95 participants at risk A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=214 participants at risk Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.47% 1/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.47% 1/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Anxiety	0.00% 0/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.47% 1/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Mania	2.1% 2/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	1.4% 3/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Persecutory delusion	0.00% 0/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.47% 1/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Psychotic disorder	2.1% 2/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.00% 0/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Schizoaffective disorder	3.2% 3/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	2.3% 5/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Suicidal ideation	1.1% 1/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.00% 0/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/95 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	0.47% 1/214 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.

Other adverse events

Measure	Placebo n=95 participants at risk A placebo control was used to establish the frequency and magnitude of changes in clinical endpoints that could occur in the absence of active treatment.	Paliperidone Extended-Release (ER) n=214 participants at risk Paliperidone (9-hydroxy-risperidone, R076477) is an atypical antipsychotic agent approved for the treatment of schizophrenia and is in development for the treatment of bipolar disorder and schizoaffective disorder. Paliperidone is a monoaminergic antagonist that exhibits the characteristic dopamine type 2 (D2) and serotonin (5-hydroxytryptamine \[5-HT\]) type 2A (5HT2A) antagonism of the newer, or second-generation, antipsychotic drugs. Paliperidone is available in an oral formulation using extended-release (ER).
Gastrointestinal disorders Dyspepsia	5.3% 5/95 • Number of events 5 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	5.6% 12/214 • Number of events 13 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Nervous system disorders Akathisia	1.1% 1/95 • Number of events 1 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	6.1% 13/214 • Number of events 14 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Nervous system disorders Dizziness	5.3% 5/95 • Number of events 5 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	8.4% 18/214 • Number of events 19 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Nervous system disorders Headache	12.6% 12/95 • Number of events 15 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	15.0% 32/214 • Number of events 38 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.
Psychiatric disorders Insomnia	5.3% 5/95 • Number of events 7 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.	6.5% 14/214 • Number of events 21 Safety Population. Safety population for Placebo is 95 subjects and for PALI ER is 214 subjects.

Additional Information

Vice President, Medical Affairs, CNS

Ortho McNeil Janssen Scientific Affairs, LLC

Phone: 609-730-2136

Email: jhulihan@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60