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 two dosages 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 3 groups to receive 6 weeks of oral treatment with 1 of 2 dosages of paliperidone ER or 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 hypotheses are that at least one of the two dosages of paliperidone ER is better than placebo on the change from baseline in the PANSS total score in acutely ill patients with schizoaffective disorder at the end of 6 weeks of treatment. Patients will receive study drug by mouth for a total of 43 days. Beginning on Day 1, patients will take either placebo or 1 of 2 doses of paliperidone: 6 mg/day (low randomized dosage) or 12 mg/day (high randomized dosage). During the first 2 weeks, dosages may be adjusted.
Interventions
DRUGPaliperidone ER
6mg/day paliperidone er for 6 weeks
DRUGPlacebo
Placebo 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 |
|---|---|---|
| Baseline Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score | 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. |
| The Change From Baseline to Week 6 or the Last Post-randomization Assessment During Double-blind Treatment in the Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score | Baseline to Week 6 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score | Baseline to Week 6 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. |
| 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. |
| Change in Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder | Baseline to Week 6 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. |
| Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | Week 6 LOCF End Point | 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. |
| Number of Participants With Response | Baseline to Week 6 LOCF End Point | Response is defined as a 30% or more reduction from baseline in PANSS total score and a CGI-C score of \<= 2. (CGI-C-SCA: Clinical Global Impression of Change for Schizoaffective Disorder). 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 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score | Baseline to Week 6 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score | Baseline to Week 6 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score | Baseline to Week 6 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. |
| Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score | Baseline to Week 6 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score | Baseline to Week 6 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. |
| Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score | Baseline to Week 6 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | Baseline to Week 6 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. |
| 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. |
| Change in Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | Baseline to Week 6 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. |
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 107 |
| Paliperidone Extended Release (ER) Low Dose Paliperidone Extended Release (ER) Low Dose - 6mg/day with option to reduce to 3mg/day | 105 |
| Paliperidone Extended Release (ER) High Dose Paliperidone Extended Release (ER) High Dose - 12mg/day with option to reduce to 9mg/day | 98 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 10 | 4 |
| Overall Study | Lack of Efficacy | 22 | 12 | 9 |
| Overall Study | Lost to Follow-up | 3 | 3 | 3 |
| Overall Study | Other | 0 | 5 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 7 | 5 |
Baseline characteristics
| Characteristic | Placebo | Paliperidone Extended Release (ER) Low Dose | Paliperidone Extended Release (ER) High Dose | Total |
|---|---|---|---|---|
| Age Continuous | 37.1 years STANDARD_DEVIATION 11.1 | 38.1 years STANDARD_DEVIATION 10 | 36.5 years STANDARD_DEVIATION 10.5 | 37.3 years STANDARD_DEVIATION 10.5 |
| Region of Enrollment India | 33 participants | 34 participants | 31 participants | 98 participants |
| Region of Enrollment Russian Federation | 12 participants | 13 participants | 11 participants | 36 participants |
| Region of Enrollment Ukraine | 23 participants | 19 participants | 21 participants | 63 participants |
| Region of Enrollment United States | 39 participants | 39 participants | 35 participants | 113 participants |
| Sex: Female, Male Female | 40 Participants | 35 Participants | 34 Participants | 109 Participants |
| Sex: Female, Male Male | 67 Participants | 70 Participants | 64 Participants | 201 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 61 / 107 | 78 / 108 | 68 / 98 |
| serious Total, serious adverse events | 6 / 107 | 10 / 108 | 2 / 98 |
Outcome results
Primary
Baseline Positive and Negative Symptoms of Schizophrenia (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.
Time frame: Baseline
Population: The Intent-to-Treat population included all randomized participants 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 | Baseline Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score | 91.6 points on a scale | Standard Deviation 12.5 |
| Paliperidone Extended Release (ER) Low Dose | Baseline Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score | 95.9 points on a scale | Standard Deviation 13 |
| Paliperidone Extended Release (ER) High Dose | Baseline Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score | 92.7 points on a scale | Standard Deviation 12.6 |
Primary
The Change From Baseline to Week 6 or the Last Post-randomization Assessment During Double-blind Treatment in the Positive and Negative Symptoms of Schizophrenia (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.
Time frame: Baseline to Week 6 Last Observation Carried Forward (LOCF) End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Change From Baseline to Week 6 or the Last Post-randomization Assessment During Double-blind Treatment in the Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score. | -21.7 points on scale | Standard Deviation 21.4 |
| Paliperidone Extended Release (ER) Low Dose | The Change From Baseline to Week 6 or the Last Post-randomization Assessment During Double-blind Treatment in the Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score. | -27.4 points on scale | Standard Deviation 22.1 |
| Paliperidone Extended Release (ER) High Dose | The Change From Baseline to Week 6 or the Last Post-randomization Assessment During Double-blind Treatment in the Positive and Negative Symptoms of Schizophrenia (PANSS) Total Score. | -30.6 points on scale | Standard Deviation 19.1 |
Comparison: One of the primary pairwise comparisons was paliperidone ER high dose vs. placebo. The Hochberg step-up procedure was used to address multiplicity. P-value for between treatment group comparisons is from an ANCOVA model with fixed-effects for treatment, concomitant medication stratum and country, and baseline value as a covariate.p-value: 0.00395% CI: [-13.8, -2.9]ANCOVA
Comparison: One of the primary pairwise comparisons was paliperidone ER low dose vs. placebo. The Hochberg step-up procedure was used to address multiplicity. P-value for between treatment group comparisons is from an ANCOVA model with fixed-effects for treatment, concomitant medication stratum and country, and baseline value as a covariate.p-value: 0.18795% CI: [-9, 1.8]ANCOVA
Secondary
Change in Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder
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.
Time frame: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population. One patient was not evaluable in the Paliperidone ER Low Dose treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder | -1.1 points on scale | Standard Deviation 1.3 |
| Paliperidone Extended Release (ER) Low Dose | Change in Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder | -1.4 points on scale | Standard Deviation 1.2 |
| Paliperidone Extended Release (ER) High Dose | Change in Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder | -1.8 points on scale | Standard Deviation 1 |
p-value: <0.00195% CI: [-0.9, -0.3]ANCOVA
p-value: 0.08395% CI: [-0.6, 0]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score | -3.4 points on a subscale | Standard Deviation 4 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score | -4.5 points on a subscale | Standard Deviation 3.8 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Anxiety/Depression Factor Score | -4.3 points on a subscale | Standard Deviation 3.7 |
p-value: 0.07195% CI: [-1.8, 0.1]ANCOVA
p-value: 0.09995% CI: [-1.7, 0.1]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score | -3.7 points on a subscale | Standard Deviation 5.2 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score | -5.0 points on a subscale | Standard Deviation 5 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Disorganized Thought Factor Score | -5.7 points on a subscale | Standard Deviation 4.8 |
p-value: 0.00495% CI: [-3.1, -0.6]ANCOVA
p-value: 0.26995% CI: [-1.9, 0.5]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score | -10.7 points on a subscale | Standard Deviation 11.6 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score | -13.9 points on a subscale | Standard Deviation 12 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) General Psychopathology Subscale Score | -15.1 points on a subscale | Standard Deviation 10.3 |
p-value: 0.00895% CI: [-6.7, -1]ANCOVA
p-value: 0.17595% CI: [-4.8, 0.9]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score | -3.0 points on a subscale | Standard Deviation 5 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score | -4.5 points on a subscale | Standard Deviation 5.7 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Factor Score | -4.0 points on a subscale | Standard Deviation 5.1 |
p-value: 0.23295% CI: [-2, 0.5]ANCOVA
p-value: 0.3195% CI: [-1.8, 0.6]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score | -3.1 points on a subscale | Standard Deviation 5.1 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score | -4.4 points on a subscale | Standard Deviation 5.6 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Negative Subscale Score | -4.2 points on a subscale | Standard Deviation 5.1 |
p-value: 0.10895% CI: [-2.3, 0.2]ANCOVA
p-value: 0.4395% CI: [-1.7, 0.7]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score | -7.9 points on subscale | Standard Deviation 6.6 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score | -9.1 points on subscale | Standard Deviation 7.1 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Subscale Score | -11.3 points on subscale | Standard Deviation 6.3 |
p-value: <0.00195% CI: [-5.1, -1.7]ANCOVA
p-value: 0.21795% CI: [-2.8, 0.6]ANCOVA
Secondary
Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score | -4.8 points on a subscale | Standard Deviation 4.4 |
| Paliperidone Extended Release (ER) Low Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score | -5.4 points on a subscale | Standard Deviation 4.8 |
| Paliperidone Extended Release (ER) High Dose | Change in Positive and Negative Symptoms of Schizophrenia (PANSS) Uncontrolled Hostility/Excitement Factor Score | -7.0 points on a subscale | Standard Deviation 4.2 |
p-value: <0.00195% CI: [-3.2, -1]ANCOVA
p-value: 0.31495% CI: [-1.7, 0.5]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.
Time frame: Week 6 LOCF End Point
Population: Intent-to-Treat population. One patient was not evaluable in the Paliperidone ER Low Dose treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | 2.9 points on a scale | Standard Deviation 1.4 |
| Paliperidone Extended Release (ER) Low Dose | Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | 2.6 points on a scale | Standard Deviation 1.3 |
| Paliperidone Extended Release (ER) High Dose | Clinical Global Impression (CGI-C) - Change for Schizoaffective Disorder | 2.2 points on a scale | Standard Deviation 1.1 |
p-value: <0.00195% CI: [-1.1, -0.4]ANOVA
p-value: 0.02995% CI: [-0.7, 0]ANOVA
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.
Time frame: Baseline
Population: Intent-to-Treat population.
| 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) Low Dose | 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) High Dose | Clinical Global Impression (CGI-S) - Severity for Schizoaffective Disorder Score at Baseline | 4.6 points on a scale | Standard Deviation 0.6 |
Secondary
Number of Participants With Response
Response is defined as a 30% or more reduction from baseline in PANSS total score and a CGI-C score of \<= 2. (CGI-C-SCA: Clinical Global Impression of Change for Schizoaffective Disorder). 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 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.
Time frame: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population. One patient was not evaluable in the Paliperidone ER Low Dose treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Response | 40 count of participants |
| Paliperidone Extended Release (ER) Low Dose | Number of Participants With Response | 57 count of participants |
| Paliperidone Extended Release (ER) High Dose | Number of Participants With Response | 62 count of participants |
p-value: 0.001Cochran-Mantel-Haenszel
p-value: 0.008Cochran-Mantel-Haenszel
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score
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: Baseline to Week 6 LOCF End Point
Population: Intent-to-Treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score | -6.7 points on a subscale | Standard Deviation 6.9 |
| Paliperidone Extended Release (ER) Low Dose | Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score | -8.0 points on a subscale | Standard Deviation 6.8 |
| Paliperidone Extended Release (ER) High Dose | Positive and Negative Symptoms of Schizophrenia (PANSS) Positive Factor Score | -9.6 points on a subscale | Standard Deviation 6.4 |
p-value: 0.00195% CI: [-4.6, -1.1]ANCOVA
p-value: 0.20995% CI: [-2.8, 0.6]ANCOVA
Other Pre-specified
Change in 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 to Week 6 LOCF End Point
Population: Intent-to-Treat population with a baseline HAM-D-21 total score of \>= 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | -9.9 points on scale | Standard Deviation 10.7 |
| Paliperidone Extended Release (ER) Low Dose | Change in Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | -13.6 points on scale | Standard Deviation 9.2 |
| Paliperidone Extended Release (ER) High Dose | Change in Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | -14.5 points on scale | Standard Deviation 9.2 |
p-value: 0.03295% CI: [-6.5, -0.3]ANCOVA
p-value: 0.01395% CI: [-6.8, -0.8]ANCOVA
Other Pre-specified
Change in 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 to Week 6 LOCF End Point
Population: Intent-to-Treat population with a baseline YMRS total score of \>= 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | -11.5 points on scale | Standard Deviation 11.4 |
| Paliperidone Extended Release (ER) Low Dose | Change in Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | -14.3 points on scale | Standard Deviation 11.8 |
| Paliperidone Extended Release (ER) High Dose | Change in Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | -19.4 points on scale | Standard Deviation 11.7 |
p-value: <0.00195% CI: [-9.9, -3.7]ANCOVA
p-value: 0.06695% CI: [-5.8, 0.2]ANCOVA
Other Pre-specified
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 population with a baseline HAM-D-21 total score of \>= 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | 24.4 points on a scale | Standard Deviation 5.9 |
| Paliperidone Extended Release (ER) Low Dose | Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | 25.2 points on a scale | Standard Deviation 6.8 |
| Paliperidone Extended Release (ER) High Dose | Hamilton Rating Scale for Depression (HAM-D-21) With Baseline HAM-D-21 Total Score >= 16 | 26.9 points on a scale | Standard Deviation 7.3 |
Other Pre-specified
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 population with a baseline YMRS total score of \>= 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | 28.5 points on a scale | Standard Deviation 6.9 |
| Paliperidone Extended Release (ER) Low Dose | Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | 28.4 points on a scale | Standard Deviation 7.4 |
| Paliperidone Extended Release (ER) High Dose | Young Mania Rating Scale (YMRS) With Baseline YMRS Total Score >= 16 | 29.9 points on a scale | Standard Deviation 8.2 |