Bipolar Disorder
Conditions
Keywords
Bipolar Disorder, Mania, Depression, Manic-Depressive Disorder
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of oral extended-release (ER) paliperidone compared with placebo in the prevention of the recurrence of mood symptoms in patients with Bipolar I Disorder who initially respond to treatment of an acute manic or mixed episode with paliperidone ER. Olanzapine was included as an active control arm, although the study is not designed to allow for a direct comparison of olanzapine with paliperidone.
Detailed description
This is a randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken), active- and placebo-controlled, parallel-group, multicenter study to evaluate the efficacy (effectiveness) and safety of paliperidone ER relative to placebo in the prevention of recurrent mood symptoms associated with Bipolar I Disorder. There are 5 phases in this study: a screening phase (lasting up to 7 days) to establish a subject's eligibility for the study,; a 3-week double-blind acute treatment phase to treat the acute or manic episode; a 12-week double-blind treatment continuation phase to establish a patient's clinical stability,; a double-blind treatment maintenance phase to measure the time to symptom recurrence that will last until the patient experiences a recurrence,; and a follow-up phase consisting of a visit approximately 1 week after the last study visit. All antipsychotic drugs and all mood stabilizers other than study drug must be discontinued before the first study drug administration. Hospitalization is required for at least the first 7 days of the acute treatment phase. At the beginning of the acute treatment phase, patients will be randomly assigned to receive ER paliperidone or olanzapine in a 4:1 ratio. Patients in the ER paliperidone group who have a clinical response at the end of the acute treatment phase, remain clinically stable throughout the continuation phase, and achieve remission for each of the last 3 weeks of the continuation phase will again be randomly assigned: they will be assigned in a 1:1 ratio to receive ER paliperidone or placebo in the maintenance phase. Patients in the olanzapine treatment group who fulfill the same criteria will continue receiving double-blind treatment with olanzapine in the maintenance phase. Measures of efficacy used are the Young Mania Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Clinical Global Impression - Bipolar Disorder - Severity of Illness Scale (CGI-BP-S), Global Assessment of Functioning (GAF), the Short Form-36 to measure health-related functional status, and the sleep visual analog scale (VAS). Safety evaluations include monitoring of adverse events, clinical laboratory tests (including urine pregnancy testing and hemoglobin A1c), 12-lead ECG, vital signs measurements, measurement of orthostatic changes in pulse and blood pressure, physical examinations (including height, body weight, and waist circumference), and monitoring of extrapyramidal symptoms using the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Rating Scale (BARS), and the Simpson Angus Scale (SAS). In addition, the Scale for Suicidal Ideation will be administered to assess suicidality. The primary hypothesis for this study is that, during the long-term treatment of patients with Bipolar I Disorder who maintain clinical stability after an acute manic or mixed episode, ER paliperidone is superior to placebo in delaying the time to recurrence of any mood symptoms associated with Bipolar I Disorder. Patients begin the acute treatment phase at 6.0 mg/day of oral ER paliperidone or 10 mg/day of oral olanzapine. Dosages may be adjusted, as needed, between 3 to 12 mg/day of ER paliperidone or 5 to 20 mg/day of olanzapine, through the end of the continuation phase. Then, in the maintenance phase, patients receive the dosage of ER paliperidone (or ER paliperidone placebo) or olanzapine reached at the end of the continuation phase. They remain on those dosages until the end of the study.
Interventions
DRUGOlanzapine
Once daily in dose range of 5 to 20 mg/day for 15 weeks, then until recurrence
DRUGPaliperidone ER
Once daily in dose range of 3 to 12 mg/day for 15 weeks, then until recurrence
DRUGPlacebo
Once daily until recurrence (only after initial 15 weeks on paliperidone ER)
Sponsors
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
* Meet DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for Bipolar I Disorder Most Recent Episode Manic or Mixed (with or without psychotic features) * have a history of at least 2 previously documented mood episodes associated with Bipolar I Disorder (1 of which must be a manic or mixed episode) that required medical treatment within the past 3 years * a total score of at least 20 on the YMRS at screening and at Day 1 of the study.
Exclusion criteria
* Meet DSM-IV criteria for any type of episode associated with bipolar disorder other than Bipolar I Disorder Most Recent Episode Manic or Mixed * Meet DSM-IV criteria for rapid cycling * Meet DSM-IV criteria for schizoaffective disorder * Known or suspected borderline or antisocial personality disorder * be, in the opinion of the investigator, at significant immediate risk for suicidal or violent behavior during the course of the study based on current status or prior history (e.g., suicide attempts during previous episodes).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | Date of randomization into the maintenance phase until the first occurrence of recurrence of any symptoms or discontinuation from the study, assessed over a period of 41 months. | Time to first recurrence of any mood symptoms (ie, manic or depressive) associated with bipolar I disorder during the maintenance phase, after maintaining clinical stability during continued treatment with paliperidone ER over a period of 15 weeks. The time period was from occurrence of acute manic or mixed episode to Week 15. This outcome was measured using combination of various scales, hospitalization for any mood symptoms, use of any medicines for an mood episode and clinical events suggestive of recurrent mood episode associated with bipolar I disorder. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | Date of randomization into the maintenance phase until the first occurrence of recurrence of manic symptoms or discontinuation from the study, assessed over a period of 41 months. | This was the key secondary efficacy end-point. Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of manic symptoms. The criterias used for this analysis were similar to criterias used for primary analysis. |
| Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder | Date of randomization into the maintenance phase until the first occurrence of recurrence of depressive symptoms or discontinuation from the study, assessed over a period of 41 months. | Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of depressive symptoms. The criterias used for this analysis were similar to criterias used for primary analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS): Change From Baseline | From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization). | This is method by which condition of patient suffering with mania is checked. In this scale patient's condition is assessed using 11 items. A severity rating is assigned to each of 11 items based on the how subject feels of his or her condition and the physicians observation of patients behavior. The range of the scale is 0 to 60. A higher score indicates a more severe condition. Change from baseline (Day 105) in the double-blind maintenance phase to the last postbaseline assessment. |
| Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization). | The CGI-BP-S rating scale is used to rate the severity of bipolar disorder, including both depressed and manic components, on a 7-point scale ranging from 1 (not ill) to 7 (very severely ill). This scale permits a global evaluation of the subject's bipolar condition at a given time. Negative Change in Score Indicates Improvement. |
| Montgomery-Asberg Depression Rating Scale (MADRS) | From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization). | The MADRS consists of 10 items covering all the important complaints which patient with depression have (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Item is scored from 0 (normal) to 6 (severe). Total score (0 to 60) is calculated by adding the scores of all 10 items. A higher score represents a more severe condition. Negative Change in Score Indicates Improvement. |
| Global Assessment of Functioning (GAF): Change From Baseline | From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization). | This scale is used when the clinical progress of a subject needs to be assessed in global terms, using a single measure. The GAF scale is rated with respect to psychological, social, and occupational functioning at the time of the assessment only. A higher score indicates a better functioning, with an overall range from 1 to 100. Positive Change in Score Indicates Improvement. |
Countries
Bulgaria, China, Costa Rica, France, Germany, India, Malaysia, Panama, Poland, Romania, Russia, Serbia, South Africa, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
The double-blind (ie, niether physician nor patient knows the treatment that the patient receives) study has 15-week acute/continuation phase followed by variable-duration maintenance phase (lasting until patient had recurrence or discontinued treatment) to assess effect of paliperidone on maintenance of remission of Bipolar I Disorder
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone ER Acute and continuation period. Paliperidone ER: Oral tablet, 3 mg/day to 12 mg/day, Once daily. | 614 |
| Olanzapine Acute and continuation period. Olanzapine: Oral tablet, 5 mg/day to 20 mg/day, Once daily. | 148 |
| Total | 762 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Acute/Continuation | Adverse Event | 62 | 13 | 0 | 0 | 0 |
| Acute/Continuation | Death | 2 | 0 | 0 | 0 | 0 |
| Acute/Continuation | Lack of Efficacy | 106 | 12 | 0 | 0 | 0 |
| Acute/Continuation | Lost to Follow-up | 23 | 7 | 0 | 0 | 0 |
| Acute/Continuation | Other | 11 | 4 | 0 | 0 | 0 |
| Acute/Continuation | Protocol Violation | 10 | 2 | 0 | 0 | 0 |
| Acute/Continuation | Withdrawal by Subject | 92 | 24 | 0 | 0 | 0 |
| Maintenance | Adverse Event | 0 | 0 | 4 | 5 | 7 |
| Maintenance | Death | 0 | 0 | 0 | 2 | 0 |
| Maintenance | Lost to Follow-up | 0 | 0 | 5 | 8 | 10 |
| Maintenance | Other | 0 | 0 | 11 | 9 | 3 |
| Maintenance | Pregnancy | 0 | 0 | 1 | 0 | 0 |
| Maintenance | Protocol Violation | 0 | 0 | 4 | 1 | 1 |
| Maintenance | Withdrawal by Subject | 0 | 0 | 26 | 28 | 18 |
Baseline characteristics
| Characteristic | Paliperidone ER | Total | Olanzapine |
|---|---|---|---|
| AgeCategorical <18 | 0 participants | 0 participants | 0 participants |
| AgeCategorical 18-25 | 98 participants | 123 participants | 25 participants |
| AgeCategorical 26-50 | 378 participants | 474 participants | 96 participants |
| AgeCategorical 51-65 | 138 participants | 165 participants | 27 participants |
| AgeCategorical >65 | 0 participants | 0 participants | 0 participants |
| Age, Categorical <=18 years | 7 Participants | 10 Participants | 3 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 606 Participants | 751 Participants | 145 Participants |
| Age, Continuous | 39.7 years STANDARD_DEVIATION 11.93 | 39.6 years STANDARD_DEVIATION 11.84 | 39.2 years STANDARD_DEVIATION 11.49 |
| Region of Enrollment Asia | 162 participants | 198 participants | 36 participants |
| Region of Enrollment Bulgaria | 27 participants | 33 participants | 6 participants |
| Region of Enrollment China | 86 participants | 106 participants | 20 participants |
| Region of Enrollment Costa Rica | 12 participants | 16 participants | 4 participants |
| Region of Enrollment Eastern Europe | 129 participants | 160 participants | 31 participants |
| Region of Enrollment European Union | 71 participants | 90 participants | 19 participants |
| Region of Enrollment Germany | 6 participants | 9 participants | 3 participants |
| Region of Enrollment India | 69 participants | 83 participants | 14 participants |
| Region of Enrollment Malaysia | 7 participants | 9 participants | 2 participants |
| Region of Enrollment Morocco | 6 participants | 8 participants | 2 participants |
| Region of Enrollment North America | 177 participants | 218 participants | 41 participants |
| Region of Enrollment Other | 75 participants | 96 participants | 21 participants |
| Region of Enrollment Panama | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Poland | 16 participants | 21 participants | 5 participants |
| Region of Enrollment Romania | 22 participants | 27 participants | 5 participants |
| Region of Enrollment Russian Federation | 51 participants | 62 participants | 11 participants |
| Region of Enrollment Serbia | 32 participants | 40 participants | 8 participants |
| Region of Enrollment South Africa | 26 participants | 32 participants | 6 participants |
| Region of Enrollment Tunisia | 10 participants | 14 participants | 4 participants |
| Region of Enrollment Turkey | 18 participants | 22 participants | 4 participants |
| Region of Enrollment Ukraine | 46 participants | 58 participants | 12 participants |
| Region of Enrollment United States | 177 participants | 218 participants | 41 participants |
| Sex: Female, Male Female | 310 Participants | 390 Participants | 80 Participants |
| Sex: Female, Male Male | 304 Participants | 372 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 351 / 614 | 79 / 148 | 38 / 147 | 38 / 149 | 26 / 83 |
| serious Total, serious adverse events | 42 / 614 | 10 / 148 | 33 / 147 | 16 / 149 | 8 / 83 |
Outcome results
Primary
Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder
Time to first recurrence of any mood symptoms (ie, manic or depressive) associated with bipolar I disorder during the maintenance phase, after maintaining clinical stability during continued treatment with paliperidone ER over a period of 15 weeks. The time period was from occurrence of acute manic or mixed episode to Week 15. This outcome was measured using combination of various scales, hospitalization for any mood symptoms, use of any medicines for an mood episode and clinical events suggestive of recurrent mood episode associated with bipolar I disorder.
Time frame: Date of randomization into the maintenance phase until the first occurrence of recurrence of any symptoms or discontinuation from the study, assessed over a period of 41 months.
Population: Intent-to-treat analysis set (ITT) in maintenance (MA) phase, which included participants who entered the MA phase and took at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pali/Placebo | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | 85.0 Days |
| Pali/Placebo | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | Median Time to Recurrence | 283.0 Days |
| Pali/Pali | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | 140.0 Days |
| Pali/Pali | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | Median Time to Recurrence | 558.0 Days |
| Olan/Olan | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | 541 Days |
| Olan/Olan | Time to Recurrence of Any Mood Symptoms (Manic or Depressive) Associated With Bipolar I Disorder | Median Time to Recurrence | NA Days |
Comparison: Null hypothesis: there is no difference between Pali/Pali and Pali/Placebo in the time to recurrence of any mood symptoms related to bipolar I disorder. An interim analysis was performed when approximately 85% of the required number of recurrences were reported in Pali/Pali and Pali/Placebo treatment groups. A flexible group-sequential approach was adopted. The general family of alpha spending function based on the rho-family with rho=2.5 at overall type I error of 0.025 (1-sided) was employed.p-value: 0.017Weighted Z- test
Secondary
Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder
Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of depressive symptoms. The criterias used for this analysis were similar to criterias used for primary analysis.
Time frame: Date of randomization into the maintenance phase until the first occurrence of recurrence of depressive symptoms or discontinuation from the study, assessed over a period of 41 months.
Population: Intent-to-treat analysis set in MA period, which included participants who entered the maintenance phase and took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pali/Placebo | Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder | 503.0 Days |
| Pali/Pali | Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder | 448.0 Days |
| Olan/Olan | Time to Recurrence of Depressive Symptoms Associated With Bipolar I Disorder | NA Days |
95% CI: [0.53, 1.46]Regression, Cox
Secondary
Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder
This was the key secondary efficacy end-point. Pali/Pali and Pali/Placebo were compared with each other with respect to time to recurrence of manic symptoms. The criterias used for this analysis were similar to criterias used for primary analysis.
Time frame: Date of randomization into the maintenance phase until the first occurrence of recurrence of manic symptoms or discontinuation from the study, assessed over a period of 41 months.
Population: Intent-to-treat analysis set in MA phase, which included participants who entered the MA phase and took at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pali/Placebo | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | 194.0 Days |
| Pali/Placebo | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | Median Time to Recurrence | 550.0 Days |
| Pali/Pali | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | 498.0 Days |
| Pali/Pali | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | Median Time to Recurrence | NA Days |
| Olan/Olan | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | 25% Quantile of Time to Recurrence | NA Days |
| Olan/Olan | Time to Recurrence of Manic Symptoms Associated With Bipolar I Disorder | Median Time to Recurrence | NA Days |
Comparison: At the time of interim analysis of the primary efficacy endpoint, the proportion of recurrence of manic symptoms was 81.9% of the number of recurrence of manic symptoms at final analysis. A flexible group-sequential approach was adopted. The general family of alpha spending function based on the rho-family with rho=2.5 at overall type I error of 0.025 (1-sided) was employed.p-value: <0.001Weighted z-test
Other Pre-specified
Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline
The CGI-BP-S rating scale is used to rate the severity of bipolar disorder, including both depressed and manic components, on a 7-point scale ranging from 1 (not ill) to 7 (very severely ill). This scale permits a global evaluation of the subject's bipolar condition at a given time. Negative Change in Score Indicates Improvement.
Time frame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Population: Intent-to-Treat
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paliperidone ER | Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | -2 Scores on the scale |
| Olanzapine | Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | -3 Scores on the scale |
| Pali/Placebo | Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | 2 Scores on the scale |
| Pali/Pali | Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | 0 Scores on the scale |
| Olan/Olan | Clinical Global Impression - Bipolar Disorder - Severity of Illness (CGI-BP-S): Change From Baseline | 0 Scores on the scale |
Comparison: Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)p-value: 0.007ANCOVA
Other Pre-specified
Global Assessment of Functioning (GAF): Change From Baseline
This scale is used when the clinical progress of a subject needs to be assessed in global terms, using a single measure. The GAF scale is rated with respect to psychological, social, and occupational functioning at the time of the assessment only. A higher score indicates a better functioning, with an overall range from 1 to 100. Positive Change in Score Indicates Improvement.
Time frame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Global Assessment of Functioning (GAF): Change From Baseline | 19.6 Scores on the scale | Standard Deviation 17.38 |
| Olanzapine | Global Assessment of Functioning (GAF): Change From Baseline | 20.8 Scores on the scale | Standard Deviation 18.26 |
| Pali/Placebo | Global Assessment of Functioning (GAF): Change From Baseline | -15.2 Scores on the scale | Standard Deviation 20.93 |
| Pali/Pali | Global Assessment of Functioning (GAF): Change From Baseline | -8.9 Scores on the scale | Standard Deviation 17.75 |
| Olan/Olan | Global Assessment of Functioning (GAF): Change From Baseline | -4.2 Scores on the scale | Standard Deviation 13.98 |
Comparison: Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)p-value: 0.0195% CI: [1.4, 10.09]ANCOVA
Other Pre-specified
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS consists of 10 items covering all the important complaints which patient with depression have (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts). Item is scored from 0 (normal) to 6 (severe). Total score (0 to 60) is calculated by adding the scores of all 10 items. A higher score represents a more severe condition. Negative Change in Score Indicates Improvement.
Time frame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Montgomery-Asberg Depression Rating Scale (MADRS) | -2.7 Scores on the scale | Standard Deviation 8.21 |
| Olanzapine | Montgomery-Asberg Depression Rating Scale (MADRS) | -2.7 Scores on the scale | Standard Deviation 7.82 |
| Pali/Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | 6.0 Scores on the scale | Standard Deviation 9.16 |
| Pali/Pali | Montgomery-Asberg Depression Rating Scale (MADRS) | 6.1 Scores on the scale | Standard Deviation 10.1 |
| Olan/Olan | Montgomery-Asberg Depression Rating Scale (MADRS) | 2.5 Scores on the scale | Standard Deviation 7.1 |
Comparison: Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)p-value: 0.76395% CI: [-1.87, 2.55]ANCOVA
Other Pre-specified
Young Mania Rating Scale (YMRS): Change From Baseline
This is method by which condition of patient suffering with mania is checked. In this scale patient's condition is assessed using 11 items. A severity rating is assigned to each of 11 items based on the how subject feels of his or her condition and the physicians observation of patients behavior. The range of the scale is 0 to 60. A higher score indicates a more severe condition. Change from baseline (Day 105) in the double-blind maintenance phase to the last postbaseline assessment.
Time frame: From 1st randomization into acute phase to end of acute/continuation phase (ie, up to 15 weeks after 1st randomization), or from randomization into maintenance (MA) phase to the end of MA phase (ie, up to 175 weeks (or 41 months) after 2nd randomization).
Population: Intent-to-Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone ER | Young Mania Rating Scale (YMRS): Change From Baseline | -19.2 Scores on the scale | Standard Deviation 11.23 |
| Olanzapine | Young Mania Rating Scale (YMRS): Change From Baseline | -19.3 Scores on the scale | Standard Deviation 10.25 |
| Pali/Placebo | Young Mania Rating Scale (YMRS): Change From Baseline | 9.0 Scores on the scale | Standard Deviation 11.78 |
| Pali/Pali | Young Mania Rating Scale (YMRS): Change From Baseline | 4.2 Scores on the scale | Standard Deviation 9.33 |
| Olan/Olan | Young Mania Rating Scale (YMRS): Change From Baseline | 1.3 Scores on the scale | Standard Deviation 6.26 |
Comparison: Change from Baseline (Maintenance Phase) to Endpoint (Maintenance Phase)p-value: <0.00195% CI: [-6.92, -1.98]ANCOVA