Bipolar Disorder Mania
Conditions
Brief summary
The purpose of the study is to determine whether aripiprazole provides additional clinical benefit to patients with Bipolar I disorder when combined with lithium or valproate over 12 weeks.
Interventions
DRUGAripiprazole
5-, 10-, or 15-mg oral tablets in titrated doses for 12 weeks
DRUGPlacebo
Tablets, Oral, 0 mg, once daily, 12 weeks
DRUGLithium
Participant's ongoing dose
DRUGValproate
Participant's ongoing dose
Sponsors
Otsuka America Pharmaceutical
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: * Clinical diagnosis of bipolar I disorder mania, manic or mixed episode, with or without psychotic features * Current ongoing lithium or valproate treatment with the possibility of benefiting, based on the investigator's clinical judgment, from adjunctive treatment with aripiprazole * Therapeutic serum levels of lithium or valproate and a Young Mania Rating Total Score of 16 or higher at screening and baseline * Participants taking current lithium or valproate treatment combined with antipsychotic medication other than aripiprazole are acceptable, provided that the other antipsychotic medication is washed out at least 3 days prior to the blood draw for therapeutic plasma levels of lithium and valproate determination. Long-acting antipsychotics must be washed out prior to entering the double-blind treatment. Key
Exclusion criteria
* Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks after the last dose of investigational product * A diagnosis of delirium, dementia, amnesia or other cognitive disorder, or a psychotic disorder * Current diagnosis of delirium, dementia, a cognitive disorder (ie, amnesia), or a psychotic disorder (ie, schizophrenia or schizoaffective disorder) * Current diagnosis of bipolar II disorder, bipolar disorder not otherwise specified, or any other primary psychiatric disorder other than bipolar I disorder mania * Thyroid pathology * Demonstrated cocaine abuse or dependence within the past 3 months prior to screening. * History of neuroleptic malignant syndrome from antipsychotic agents * Manic symptoms that investigator considers refractory to treatment * Previous nonresponsive (by investigator judgment) to aripiprazole for manic symptoms * Significant risk of suicide based on history, mental status exam, or investigator judgment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set) | Baseline to Week 12 | The YMRS is a clinician-administered scale, consisting of 11 multiple choice items, and used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-though disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Baseline to Weeks 3, 6, 9, and 12 | Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward. |
| Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set) | Baseline to Week 12 | Adjusted mean change. The CGI-BP is scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward. |
| Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Baseline to Weeks 3, 6, 9, and 12 | The FAST is an interview-administered instrument used to assess the main functioning problems that patients with bipolar disorder experience. Participants are rated at Baseline, Week 3, Week 6, Week 9, and Week 12/End of Study Visit. The FAST consists of 24 items that assess impairment or disability in 6 specific areas of functioning, categorized as the subscales: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal (IP) relationships, and leisure time. All items are rated using a 4-point scale, 0=no difficulty, 1=mild difficulty, 2=moderate difficulty, and 3=severe difficulty. The global score is the sum of the scores of all items and ranges from 0 (0\*24)to 96 (4\*24). The higher the global score, the higher the level of impairment. function=functioning. LOCF=last observation carried forward. |
| Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Baseline to Weeks 3, 6, 9, and 12 | Response on the YMRS is defined as a 50% or greater improvement from baseline in YMRS total score. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. OC=observed cases. |
| Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Baseline to Weeks 3,6, 9, and 12 | Remission is defined as a YMRS total score of 12 or less. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward. |
| Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Baseline to Weeks 3, 6, 9, and 12 | Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward. |
| Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Baseline to Weeks 3, 6, 9, and 12 | Adjusted Mean Scores. The PGI-I is a self-administered 7-point scale, with scores ranging from 1 (very much improved) to 7 (very much worse), that assesses the improvement or worsening of a patient's illness relative to baseline at the beginning of the intervention. Scores: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. OC=observed cases. |
| Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Baseline to Weeks 3, 6, 9, and 12 | Adjusted mean change.OC=observed cases; LOCF=last observation carried forward. |
| Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set) | Baseline to Weeks 3, 6, 9, and12 | Relevant weight gain=7% or greater increase in weight; relevant weight loss=7% or greater decrease in weight. LOCF=last observation carried forward. |
| Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set) | Baseline to Week 12 | BMI=Weight in kilograms /(Height in meters\^2). LOCF=last observation carried forward. |
| Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Baseline to Weeks 6 and 12 | Adjusted mean change. The LIFE-RIFT total score ranges from 4 to 20 and is the sum of scores of 4 items: work, interpersonal relations, satisfaction, and recreation. A negative change score signifies improvement. OC=observed cases; LOCF=last observation carried forward. |
Countries
Austria, Czechia, France, Germany, Greece, Hungary, Italy, Poland, Romania, Russia, South Africa, Spain, Turkey (Türkiye)
Participant flow
Pre-assignment details
Of 493 participants enrolled, 370 were randomized, and 369 received treatment with double-blind study medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Valproate or Lithium Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. | 189 |
| Aripiprazole + Valproate or Lithium Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12. | 181 |
| Total | 370 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 25 | 23 |
| Overall Study | Lack of Efficacy | 11 | 10 |
| Overall Study | Lost to Follow-up | 3 | 5 |
| Overall Study | No longer meets study criteria | 0 | 1 |
| Overall Study | Other reasons | 4 | 1 |
| Overall Study | Poor compliance/noncompliance | 3 | 5 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 14 |
Baseline characteristics
| Characteristic | Aripiprazole + Valproate or Lithium | Total | Placebo + Valproate or Lithium |
|---|---|---|---|
| Age Continuous | 44.37 Years STANDARD_DEVIATION 12.13 | 44.65 Years STANDARD_DEVIATION 12.57 | 44.92 Years STANDARD_DEVIATION 12.99 |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 6 Participants | 12 Participants | 6 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 172 Participants | 351 Participants | 179 Participants |
| Sex: Female, Male Female | 101 Participants | 200 Participants | 99 Participants |
| Sex: Female, Male Male | 80 Participants | 170 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 180 | 29 / 189 |
| serious Total, serious adverse events | 11 / 180 | 17 / 189 |
Outcome results
Primary
Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)
The YMRS is a clinician-administered scale, consisting of 11 multiple choice items, and used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-though disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
Time frame: Baseline to Week 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set) | -11.54 Units on a scale | Standard Error 0.78 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set) | -13.57 Units on a scale | Standard Error 0.78 |
p-value: 0.05895% CI: [-4.14, 0.07]ANCOVA
Secondary
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Adjusted mean change.OC=observed cases; LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 6 (n=152,144) | -0.02 Kilograms | Standard Error 0.2 |
| Placebo + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 12 (n=133, 123) | 0.22 Kilograms | Standard Error 0.29 |
| Placebo + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 9 (n=142, 128) | 0.07 Kilograms | Standard Error 0.26 |
| Placebo + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 12 (LOCF) (n=183, 174) | 0.11 Kilograms | Standard Error 0.24 |
| Placebo + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 3 (n=177, 171) | -0.06 Kilograms | Standard Error 0.16 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 12 (LOCF) (n=183, 174) | 0.11 Kilograms | Standard Error 0.23 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 3 (n=177, 171) | 0.14 Kilograms | Standard Error 0.15 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 6 (n=152,144) | 0.29 Kilograms | Standard Error 0.21 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 9 (n=142, 128) | -0.01 Kilograms | Standard Error 0.26 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set) | Week 12 (n=133, 123) | 0.02 Kilograms | Standard Error 0.29 |
p-value: 0.98395% CI: [-0.63, 0.64]ANOVA/ANCOVA model
Secondary
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 3 (n=183, 174) | -0.01 Units on a scale | Standard Error 0.05 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 6 (n=186, 176) | -0.02 Units on a scale | Standard Error 0.06 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 9 (n=186, 176) | -0.04 Units on a scale | Standard Error 0.07 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 12 (n=186, 176) | -0.03 Units on a scale | Standard Error 0.08 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 12 (n=186, 176) | 0.14 Units on a scale | Standard Error 0.08 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 3 (n=183, 174) | -0.09 Units on a scale | Standard Error 0.05 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 9 (n=186, 176) | 0.11 Units on a scale | Standard Error 0.07 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set) | Week 6 (n=186, 176) | -0.01 Units on a scale | Standard Error 0.06 |
p-value: 0.2495% CI: [-0.22, 0.06]ANOVA/ANCOVA model
p-value: 0.84395% CI: [-0.15, 0.19]ANOVA/ANCOVA model
p-value: 0.11795% CI: [-0.04, 0.35]ANOVA/ANCOVA model
p-value: 0.10995% CI: [-0.04, 0.38]ANOVA/ANCOVA model
Secondary
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 3 (n=183, 174) | -0.97 Units on a scale | Standard Error 0.08 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 6 (n=186, 176) | -1.35 Units on a scale | Standard Error 0.09 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 9 (n=186, 176) | -1.55 Units on a scale | Standard Error 0.1 |
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 12 (n=186, 176) | -1.78 Units on a scale | Standard Error 0.11 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 12 (n=186, 176) | -2.07 Units on a scale | Standard Error 0.11 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 3 (n=183, 174) | -0.93 Units on a scale | Standard Error 0.08 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 9 (n=186, 176) | -1.83 Units on a scale | Standard Error 0.11 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set) | Week 6 (n=186, 176) | -1.46 Units on a scale | Standard Error 0.1 |
p-value: 0.66995% CI: [-0.16, 0.25]ANOVA/ANCOVA
p-value: 0.43695% CI: [-0.36, 0.16]ANOVA/ANCOVA
p-value: 0.05395% CI: [-0.56, 0]ANOVA/ANCOVA
p-value: 0.04495% CI: [-0.59, -0.01]ANOVA/ANCOVA
Secondary
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set)
Adjusted mean change. The CGI-BP is scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Time frame: Baseline to Week 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set) | -1.51 Units on a scale | Standard Error 0.11 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set) | -1.59 Units on a scale | Standard Error 0.11 |
p-value: 0.56795% CI: [-0.37, 0.2]ANOVA/ANCOVA model
Secondary
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
The FAST is an interview-administered instrument used to assess the main functioning problems that patients with bipolar disorder experience. Participants are rated at Baseline, Week 3, Week 6, Week 9, and Week 12/End of Study Visit. The FAST consists of 24 items that assess impairment or disability in 6 specific areas of functioning, categorized as the subscales: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal (IP) relationships, and leisure time. All items are rated using a 4-point scale, 0=no difficulty, 1=mild difficulty, 2=moderate difficulty, and 3=severe difficulty. The global score is the sum of the scores of all items and ranges from 0 (0\*24)to 96 (4\*24). The higher the global score, the higher the level of impairment. function=functioning. LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 outcomes research evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 9 (n=182, 171) | -2.30 Units on a scale | Standard Error 0.26 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 3 (n=179, 169) | -0.93 Units on a scale | Standard Error 0.18 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 12 (n=182, 171) | -2.59 Units on a scale | Standard Error 0.27 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 3 (n=179, 169) | -0.65 Units on a scale | Standard Error 0.25 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 3 (n=179,169) | -1.57 Units on a scale | Standard Error 0.25 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 6 (n=182, 171) | -8.59 Units on a scale | Standard Error 0.98 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 6 (n=182, 171) | -2.20 Units on a scale | Standard Error 0.28 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 6 (n=182, 171) | -1.23 Units on a scale | Standard Error 0.29 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 9 (n=182, 171) | -2.41 Units on a scale | Standard Error 0.31 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 6 (n=182, 171) | -1.44 Units on a scale | Standard Error 0.19 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 12 (n=182, 171) | -2.57 Units on a scale | Standard Error 0.31 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 9 (n=182, 171) | -1.20 Units on a scale | Standard Error 0.3 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 3 (n=179, 169) | -0.50 Units on a scale | Standard Error 0.11 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 12 (n=182, 171) | -10.39 Units on a scale | Standard Error 1.09 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 6 (n=182, 171) | -0.53 Units on a scale | Standard Error 0.13 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 12 (n=182, 171) | -1.49 Units on a scale | Standard Error 0.3 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 9 (n=182, 171) | -0.52 Units on a scale | Standard Error 0.13 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 9 (n=182, 171) | -1.56 Units on a scale | Standard Error 0.21 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 12 (n=182, 171) | -0.68 Units on a scale | Standard Error 0.13 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 3 (n=179, 169) | -1.33 Units on a scale | Standard Error 0.23 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 3 (n=179, 169) | -0.78 Units on a scale | Standard Error 0.12 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 9 (n=182, 171) | -9.18 Units on a scale | Standard Error 1.06 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 6 (n=182, 171) | -1.16 Units on a scale | Standard Error 0.12 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 6 (n=182, 171) | -2.12 Units on a scale | Standard Error 0.26 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 9 (n=182, 171) | -1.25 Units on a scale | Standard Error 0.13 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 12 (n=182, 171) | -1.84 Units on a scale | Standard Error 0.21 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 12 (n=182, 171) | -1.30 Units on a scale | Standard Error 0.12 |
| Placebo + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 3 (n=179, 169) | -5.68 Units on a scale | Standard Error 0.86 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 12 (n=182, 171) | -1.07 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 3 (n=179, 169) | -5.00 Units on a scale | Standard Error 0.87 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 6 (n=182, 171) | -6.93 Units on a scale | Standard Error 0.99 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 9 (n=182, 171) | -7.71 Units on a scale | Standard Error 1.07 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Total score: Week 12 (n=182, 171) | -8.51 Units on a scale | Standard Error 1.1 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 3 (n=179, 169) | -0.93 Units on a scale | Standard Error 0.18 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 6 (n=182, 171) | -1.11 Units on a scale | Standard Error 0.19 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 9 (n=182, 171) | -1.20 Units on a scale | Standard Error 0.21 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Autonomy score: Week 12 (n=182, 171) | -1.45 Units on a scale | Standard Error 0.21 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 3 (n=179, 169) | -1.00 Units on a scale | Standard Error 0.25 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 6 (n=182, 171) | -1.40 Units on a scale | Standard Error 0.29 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 9 (n=182, 171) | -1.22 Units on a scale | Standard Error 0.3 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Occupational function score: Week 12 (n=182, 171) | -1.24 Units on a scale | Standard Error 0.3 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 3 (n=179, 169) | -0.99 Units on a scale | Standard Error 0.23 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 6 (n=182, 171) | -1.46 Units on a scale | Standard Error 0.26 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 9 (n=182, 171) | -1.68 Units on a scale | Standard Error 0.27 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Cognitive function score: Week 12 (n=182, 171) | -1.91 Units on a scale | Standard Error 0.28 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 3 (n=179,169) | -1.33 Units on a scale | Standard Error 0.26 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 6 (n=182, 171) | -1.91 Units on a scale | Standard Error 0.29 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 9 (n=182, 171) | -2.14 Units on a scale | Standard Error 0.31 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | IP relationships score: Week 12 (n=182, 171) | -2.31 Units on a scale | Standard Error 0.31 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 3 (n=179, 169) | -0.28 Units on a scale | Standard Error 0.11 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 6 (n=182, 171) | -0.34 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 9 (n=182, 171) | -0.52 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Leisure time score: Week 12 (n=182, 171) | -0.59 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 3 (n=179, 169) | -0.48 Units on a scale | Standard Error 0.12 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 6 (n=182, 171) | -0.76 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set) | Financial issues score: Week 9 (n=182, 171) | -0.99 Units on a scale | Standard Error 0.13 |
p-value: 0.56695% CI: [-1.66, 3.03]ANCOVA
p-value: 0.22195% CI: [-1, 4.32]ANCOVA
p-value: 0.31595% CI: [-1.4, 4.35]ANCOVA
p-value: 0.21295% CI: [-1.08, 4.84]ANCOVA
p-value: 0.99195% CI: [-0.49, 0.48]ANCOVA
p-value: 0.20195% CI: [-0.18, 0.85]ANCOVA
p-value: 0.19895% CI: [-0.19, 0.93]ANCOVA
p-value: 0.17895% CI: [-0.18, 0.96]ANCOVA
p-value: 0.31195% CI: [-1.01, 0.32]ANCOVA
p-value: 0.67195% CI: [-0.94, 0.61]ANCOVA
p-value: 0.96895% CI: [-0.83, 0.79]ANCOVA
p-value: 0.54695% CI: [-0.56, 1.07]ANCOVA
p-value: 0.28495% CI: [-0.28, 0.96]ANCOVA
p-value: 0.06395% CI: [-0.04, 1.35]ANCOVA
p-value: 0.0995% CI: [-0.1, 1.34]ANCOVA
p-value: 0.07295% CI: [-0.06, 1.42]ANCOVA
p-value: 0.49995% CI: [-0.45, 0.93]ANCOVA
p-value: 0.45795% CI: [-0.48, 1.06]ANCOVA
p-value: 0.52595% CI: [-0.56, 1.1]ANCOVA
p-value: 0.54495% CI: [-0.58, 1.09]ANCOVA
p-value: 0.14995% CI: [-0.08, 0.52]ANCOVA
p-value: 0.26495% CI: [-0.15, 0.54]ANCOVA
p-value: 0.98895% CI: [-0.35, 0.35]ANCOVA
p-value: 0.64195% CI: [-0.27, 0.44]ANCOVA
p-value: 0.06895% CI: [-0.02, 0.61]ANCOVA
p-value: 0.01995% CI: [0.07, 0.74]ANCOVA
p-value: 0.13695% CI: [-0.08, 0.6]ANCOVA
p-value: 0.1895% CI: [-0.11, 0.57]ANCOVA
Secondary
Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set)
Adjusted mean change. The LIFE-RIFT total score ranges from 4 to 20 and is the sum of scores of 4 items: work, interpersonal relations, satisfaction, and recreation. A negative change score signifies improvement. OC=observed cases; LOCF=last observation carried forward.
Time frame: Baseline to Weeks 6 and 12
Population: All randomized participants who received at least 1 dose of study medication and had at least 1 outcome research evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 6 (n=146, 135) | -2.13 Units on a scale | Standard Error 0.22 |
| Placebo + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 12 (n=123, 115) | -3.20 Units on a scale | Standard Error 0.28 |
| Placebo + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 12 (LOCF) (n=165, 150) | -2.30 Units on a scale | Standard Error 0.27 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 6 (n=146, 135) | -1.45 Units on a scale | Standard Error 0.23 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 12 (n=123, 115) | -2.37 Units on a scale | Standard Error 0.28 |
| Aripiprazole + Valproate or Lithium | Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set) | Week 12 (LOCF) (n=165, 150) | -1.69 Units on a scale | Standard Error 0.28 |
95% CI: [0.07, 1.29]ANOVA/ANCOVA model
p-value: 0.03195% CI: [0.08, 1.58]ANOVA/ANCOVA model
p-value: 0.10495% CI: [-0.13, 1.34]ANOVA/ANCOVA model
Secondary
Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set)
BMI=Weight in kilograms /(Height in meters\^2). LOCF=last observation carried forward.
Time frame: Baseline to Week 12
Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + Valproate or Lithium | Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set) | 0.0 kg/m^2 |
| Aripiprazole + Valproate or Lithium | Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set) | 0.0 kg/m^2 |
p-value: 0.582ANCOVA
Secondary
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
Adjusted Mean Scores. The PGI-I is a self-administered 7-point scale, with scores ranging from 1 (very much improved) to 7 (very much worse), that assesses the improvement or worsening of a patient's illness relative to baseline at the beginning of the intervention. Scores: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. OC=observed cases.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 outcomes research evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 3 (n=178, 168) | 2.94 Units on a scale | Standard Error 0.1 |
| Placebo + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 6 (n=151, 140) | 2.39 Units on a scale | Standard Error 0.11 |
| Placebo + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 12 (n=127, 119) | 2.02 Units on a scale | Standard Error 0.12 |
| Placebo + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 12 (LOCF) (n=181, 173) | 2.60 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 12 (LOCF) (n=181, 173) | 2.88 Units on a scale | Standard Error 0.13 |
| Aripiprazole + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 3 (n=178, 168) | 2.99 Units on a scale | Standard Error 0.1 |
| Aripiprazole + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 12 (n=127, 119) | 2.24 Units on a scale | Standard Error 0.12 |
| Aripiprazole + Valproate or Lithium | Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set) | Week 6 (n=151, 140) | 2.64 Units on a scale | Standard Error 0.11 |
95% CI: [-0.21, 0.32]ANCOVA
95% CI: [-0.05, 0.53]ANCOVA
p-value: 0.19795% CI: [-0.11, 0.54]ANCOVA
p-value: 0.11195% CI: [-0.07, 0.63]ANCOVA
Secondary
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
Response on the YMRS is defined as a 50% or greater improvement from baseline in YMRS total score. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. OC=observed cases.
Time frame: Baseline to Weeks 3, 6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 3 (n=183, 174) | 26.2 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 9 (n=186, 176) | 53.8 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 12 (n=186, 176) | 61.3 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 6 (n=186, 176) | 46.2 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 12 (n=186, 176) | 68.8 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 3 (n=183, 174) | 29.3 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 6 (n=186, 176) | 49.4 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set) | Week 9 (n=186, 176) | 64.2 Percentage of participants |
p-value: 0.46695% CI: [0.81, 1.59]Ration of response
p-value: 0.5495% CI: [0.86, 1.32]Risk ratio
p-value: 0.0695% CI: [0.99, 1.38]Risk ratio
p-value: 0.28995% CI: [0.94, 1.23]Risk ratio
Secondary
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
Remission is defined as a YMRS total score of 12 or less. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3,6, 9, and 12
Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 3 (n=183, 174) | 30.6 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 6 (n=186, 176) | 48.9 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 9 (n=186, 176) | 57.0 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 12 (n=186, 176) | 64.0 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 12 (n=186, 176) | 69.9 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 3 (n=183, 174) | 31.0 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 9 (n=186, 176) | 65.9 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set) | Week 6 (n=186, 176) | 51.7 Percentage of participants |
p-value: 0.90995% CI: [0.75, 1.39]Risk ratio (RR)
p-value: 0.57395% CI: [0.86, 1.3]RR
p-value: 0.0895% CI: [0.98, 1.36]RR
p-value: 0.21195% CI: [0.95, 1.27]RR
Secondary
Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)
Relevant weight gain=7% or greater increase in weight; relevant weight loss=7% or greater decrease in weight. LOCF=last observation carried forward.
Time frame: Baseline to Weeks 3, 6, 9, and12
Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + Valproate or Lithium | Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set) | Weight gain: Week 12 (n=184,174) | 4.3 Percentage of participants |
| Placebo + Valproate or Lithium | Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set) | Weight loss: Week 12 (n=184,174) | 2.7 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set) | Weight gain: Week 12 (n=184,174) | 5.2 Percentage of participants |
| Aripiprazole + Valproate or Lithium | Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set) | Weight loss: Week 12 (n=184,174) | 4.0 Percentage of participants |
95% CI: [0.57, 3.71]Risk Ratio