Psychotic Disorder, Schizoaffective Disorder
Conditions
Keywords
Schizoaffective Disorder, antipsychotic, paliperidone, placebo
Brief summary
The purpose of this study is to measure the effectiveness and assess the safety of different dosages (from 3 mg/day to 12 mg/day) of the antipsychotic paliperidone extended-release (ER) in patients who are experiencing an acute episode of schizoaffective disorder.
Detailed description
Schizophrenia and schizoaffective disorder are closely related in terms of symptoms, coexisting conditions, and genetic risk. In previous studies in patients with schizophrenia, treatment with paliperidone extended-release (ER) improved psychotic symptoms, as well as mood symptoms evaluated by anxiety/depression and hostility/excitement Positive and Negative Symptoms of Schizophrenia (PANSS) factor scores. Therefore, paliperidone ER may also be effective in treating symptoms of schizoaffective disorder. Paliperidone's limited potential for drug-drug interaction is particularly important in this patient population, in which multiple drug therapy is relatively common. This multicenter, double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo-controlled, parallel-group study is designed to examine the effectiveness and safety of paliperidone ER in adult patients with schizoaffective disorder who are experiencing an acute episode of this disorder. Patients in the study will be randomly assigned to 1 of 2 groups to receive 6 weeks of oral treatment with flexible dosages of paliperidone ER (3-12 mg/day) or with placebo. The primary efficacy outcome will be the change from baseline to Week 6, or the last post-randomization assessment during double-blind treatment (endpoint), in the PANSS total score. Safety will be assessed by monitoring adverse events, clinical laboratory testing, pregnancy testing, vital signs measurements, physical examination, administration of a 12-lead ECG, movement disorders side effect scales, and the InterSePT Scale for Suicidal Thinking. Patients may also choose to participate in a pharmacogenomic (DNA) analysis. The primary study hypothesis is that flexible-dose paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder. Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or paliperidone ER 6 mg/day. After day 4, dosages may be adjusted, at defined intervals, to a dosage between 3 mg/day and 12 mg/day, inclusive.
Interventions
DRUGPlacebo
for 6 weeks
DRUGPaliperidone ER
(3-12mg/day in 3 mg/day increments for 6 weeks)
Sponsors
Janssen, LP
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Diagnostic and Statistical Manual - Fourth Edition (DSM-IV) diagnosis of schizoaffective disorder * A total Positive and Negative Symptoms of Schizophrenia (PANSS) score of \>= 60 * A score of \>= 16 on Young Mania Rating Scale (YMRS) or a score of \>= 16 on the Hamilton Depression Rating Scale (HAM-D 21)
Exclusion criteria
* A primary active mental illness diagnosis other than schizoaffective disorder * Patients with first episode psychosis * Active substance dependence within previous 6 months * Treatment with clozapine within 6 months of randomization * A history of treatment resistance, defined by failure to respond to 2 adequate trials of antipsychotic medication * Pregnancy, breast-feeding, or planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline. | Baseline | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline | Baseline | 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. |
| Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Participants With Response | Week 6 LOCF End Point | 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). |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| 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. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | Baseline | 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. |
| 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. | Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment | 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. |
| Baseline Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | Baseline | 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. |
Countries
India, Malaysia, Philippines, Romania, South Korea, United States
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 93 |
| 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). | 211 |
| Total | 304 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 13 |
| Overall Study | Lack of Efficacy | 16 | 22 |
| Overall Study | Lost to Follow-up | 7 | 13 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 27 |
Baseline characteristics
| Characteristic | Paliperidone Extended-Release (ER) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 9.1 | 37.6 years STANDARD_DEVIATION 9.2 | 37.3 years STANDARD_DEVIATION 9.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 61 Participants | 90 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 55 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 109 Participants | 156 Participants | 47 Participants |
| Sex: Female, Male Female | 95 Participants | 134 Participants | 39 Participants |
| Sex: Female, Male Male | 116 Participants | 170 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 95 | 66 / 214 |
| serious Total, serious adverse events | 8 / 95 | 11 / 214 |
Outcome results
Primary
Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline.
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline. | 91.7 points on a scale | Standard Deviation 12.1 |
| Paliperidone Extended-Release (ER) | Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score at Baseline. | 92.3 points on a scale | Standard Deviation 13.5 |
p-value: 0.77495% CI: [-2.7, 3.7]ANOVA
Primary
Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -20.0 points on a scale | Standard Deviation 18.9 |
p-value: <0.00195% CI: [-13.8, -4.9]ANCOVA
Secondary
Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder
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.
Time frame: Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | 3.4 points on a scale | Standard Deviation 1.5 |
| Paliperidone Extended-Release (ER) | Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | 2.8 points on a scale | Standard Deviation 1.3 |
p-value: <0.00195% CI: [-0.9, -0.3]ANOVA
Secondary
Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -1.2 points on a scale | Standard Deviation 1.2 |
p-value: 0.00295% CI: [-0.7, -0.2]ANCOVA
Secondary
Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline
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.
Time frame: Baseline
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline | 4.6 points on a scale | Standard Deviation 0.6 |
| Paliperidone Extended-Release (ER) | Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline | 4.6 points on a scale | Standard Deviation 0.7 |
Secondary
Participants With Response
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).
Time frame: Week 6 LOCF End Point
Population: Intent-to-Treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Participants With Response | 26 participants |
| Paliperidone Extended-Release (ER) | Participants With Response | 85 participants |
p-value: 0.046Cochran-Mantel-Haenszel
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -3.3 points on a scale | Standard Deviation 3.7 |
p-value: 0.01695% CI: [-1.8, -0.2]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -3.3 points on a scale | Standard Deviation 4.5 |
p-value: <0.00195% CI: [-2.9, -0.9]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -9.7 points on a scale | Standard Deviation 9.9 |
p-value: <0.00195% CI: [-6.8, -2.3]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -3.1 points on a scale | Standard Deviation 5.2 |
p-value: <0.00195% CI: [-3.3, -0.9]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -3.0 points on a scale | Standard Deviation 4.9 |
p-value: <0.00195% CI: [-3.1, -0.8]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -6.0 points on a scale | Standard Deviation 6.9 |
p-value: <0.00195% CI: [-4.2, -1.1]ANCOVA
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -7.3 points on a scale | Standard Deviation 6.9 |
p-value: <0.00195% CI: [-4.4, -1.2]ANCOVA
Secondary
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.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -4.3 points on a scale | Standard Deviation 4.4 |
p-value: 0.00195% CI: [-2.6, -0.6]ANCOVA
Other Pre-specified
Baseline Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16
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.
Time frame: Baseline
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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 6 |
Other Pre-specified
Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16
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.
Time frame: Baseline
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | 26.9 points on a scale | Standard Deviation 8.1 |
| Paliperidone Extended-Release (ER) | Baseline Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | 27.5 points on a scale | Standard Deviation 7 |
Other Pre-specified
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.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -10.2 points on a scale | Standard Deviation 8.7 |
p-value: <0.00195% CI: [-6.4, -1.7]ANCOVA
Other Pre-specified
Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 - Change From Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point.
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.
Time frame: Change from baseline to Week 6 or the last post-randomization assessment during double-blind treatment
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| Paliperidone 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. | -10.6 points on a scale | Standard Deviation 10.8 |
p-value: 0.00195% CI: [-7.7, -2]ANCOVA