Trial Outcomes & Findings for A Study of Aripiprazole (Abilify) in Patients With Bipolar Mania (NCT NCT00261443)
NCT ID: NCT00261443
Last Updated: 2023-04-18
Results Overview
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS \> 16 and/or a MADRS \> 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS \> 16 and/or a MADRS \> 16.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1270 participants
Primary outcome timeframe
Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])
Results posted on
2023-04-18
Participant Flow
Participant milestones
| Measure |
Pre-Randomized Participants
Phase 1 (2 to 8 Week Screening, Washout and Confirmation of Partial Nonresponse Phase): lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml. Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Placebo
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Aripiprazole
Phase 3 (52 Week Assessment of Relapse Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
|---|---|---|---|
|
1: Confirmation of Partial Nonresponse
STARTED
|
1270
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
COMPLETED
|
686
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
NOT COMPLETED
|
584
|
0
|
0
|
|
2: Stability & Maintenance of Stability
STARTED
|
686
|
0
|
0
|
|
2: Stability & Maintenance of Stability
COMPLETED
|
346
|
0
|
0
|
|
2: Stability & Maintenance of Stability
NOT COMPLETED
|
340
|
0
|
0
|
|
3: Assessment of Relapse
STARTED
|
0
|
169
|
168
|
|
3: Assessment of Relapse
COMPLETED
|
0
|
89
|
103
|
|
3: Assessment of Relapse
NOT COMPLETED
|
0
|
80
|
65
|
|
4: Extension Phase
STARTED
|
0
|
19
|
23
|
|
4: Extension Phase
COMPLETED
|
0
|
16
|
21
|
|
4: Extension Phase
NOT COMPLETED
|
0
|
3
|
2
|
Reasons for withdrawal
| Measure |
Pre-Randomized Participants
Phase 1 (2 to 8 Week Screening, Washout and Confirmation of Partial Nonresponse Phase): lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml. Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Placebo
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Aripiprazole
Phase 3 (52 Week Assessment of Relapse Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
|---|---|---|---|
|
1: Confirmation of Partial Nonresponse
Adverse Event
|
33
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Withdrawal by Subject
|
93
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Lost to Follow-up
|
111
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Poor/Noncompliance
|
23
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Pregnancy
|
1
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Subject No Longer Met Study Criteria
|
307
|
0
|
0
|
|
1: Confirmation of Partial Nonresponse
Other Reasons
|
16
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Lack of Efficacy
|
43
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Adverse Event
|
93
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Withdrawal by Subject
|
65
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Lost to Follow-up
|
59
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Poor/Noncompliance
|
33
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Pregnancy
|
1
|
0
|
0
|
|
2: Stability & Maintenance of Stability
subject No Longer Met Study Criteria
|
32
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Administrative Reason by Sponsor
|
1
|
0
|
0
|
|
2: Stability & Maintenance of Stability
Other Reasons
|
13
|
0
|
0
|
|
3: Assessment of Relapse
Lack of Efficacy
|
0
|
31
|
14
|
|
3: Assessment of Relapse
Adverse Event
|
0
|
15
|
19
|
|
3: Assessment of Relapse
Withdrawal by Subject
|
0
|
14
|
15
|
|
3: Assessment of Relapse
Death
|
0
|
0
|
1
|
|
3: Assessment of Relapse
Lost to Follow-up
|
0
|
7
|
6
|
|
3: Assessment of Relapse
Poor/Noncompliance
|
0
|
5
|
3
|
|
3: Assessment of Relapse
Pregnancy
|
0
|
2
|
1
|
|
3: Assessment of Relapse
Subject No Longer Meets Study Criteria
|
0
|
2
|
1
|
|
3: Assessment of Relapse
Administrative Reason By Sponsor
|
0
|
0
|
2
|
|
3: Assessment of Relapse
Other Reasons
|
0
|
4
|
3
|
|
4: Extension Phase
Adverse Event
|
0
|
1
|
0
|
|
4: Extension Phase
Withdrawal by Subject
|
0
|
1
|
2
|
|
4: Extension Phase
Lost to Follow-up
|
0
|
1
|
0
|
Baseline Characteristics
A Study of Aripiprazole (Abilify) in Patients With Bipolar Mania
Baseline characteristics by cohort
| Measure |
Placebo
n=169 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=168 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Total
n=337 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.8 years
STANDARD_DEVIATION 12.29 • n=5 Participants
|
39.2 years
STANDARD_DEVIATION 12.43 • n=7 Participants
|
39.0 years
STANDARD_DEVIATION 12.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
98 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
185 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
71 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
152 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
112 participants
n=5 Participants
|
118 participants
n=7 Participants
|
230 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
19 participants
n=5 Participants
|
12 participants
n=7 Participants
|
31 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
33 participants
n=5 Participants
|
34 participants
n=7 Participants
|
67 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
55 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Non-US
|
111 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
218 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
58 participants
n=5 Participants
|
61 participants
n=7 Participants
|
119 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
18 participants
n=5 Participants
|
14 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
28 participants
n=5 Participants
|
27 participants
n=7 Participants
|
55 participants
n=5 Participants
|
|
Region of Enrollment
Croatia
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
17 participants
n=5 Participants
|
15 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Region of Enrollment
India
|
33 participants
n=5 Participants
|
34 participants
n=7 Participants
|
67 participants
n=5 Participants
|
|
Body Mass Index (BMI) Category
<18.5 kg/m^2
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Body Mass Index (BMI) Category
18.5 kg/m^2 to <25 kg/m^2
|
58 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Body Mass Index (BMI) Category
25 kg/m^2 to <30 kg/m^2
|
50 Participants
n=5 Participants
|
63 Participants
n=7 Participants
|
113 Participants
n=5 Participants
|
|
Body Mass Index (BMI) Category
>= 30 kg/m^2
|
56 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
112 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
28.7 kg/m^2
STANDARD_DEVIATION 7.72 • n=5 Participants
|
28.5 kg/m^2
STANDARD_DEVIATION 6.00 • n=7 Participants
|
28.6 kg/m^2
STANDARD_DEVIATION 6.90 • n=5 Participants
|
|
CGI-BP Change from Preceding Phase Score (Depression)
|
3.0 units on a scale
STANDARD_DEVIATION 1.34 • n=5 Participants
|
3.0 units on a scale
STANDARD_DEVIATION 1.31 • n=7 Participants
|
3.0 units on a scale
STANDARD_DEVIATION 1.32 • n=5 Participants
|
|
CGI-BP Change from Preceding Phase Score (Mania)
|
1.6 units on a scale
STANDARD_DEVIATION 0.81 • n=5 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 0.63 • n=7 Participants
|
1.5 units on a scale
STANDARD_DEVIATION 0.72 • n=5 Participants
|
|
CGI-BP Change from Preceding Phase Score (Overall)
|
1.6 units on a scale
STANDARD_DEVIATION 0.85 • n=5 Participants
|
1.5 units on a scale
STANDARD_DEVIATION 0.69 • n=7 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 0.77 • n=5 Participants
|
|
CGI-BP Severity of Illness Score (Depression)
|
1.3 units on a scale
STANDARD_DEVIATION 0.57 • n=5 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 0.70 • n=7 Participants
|
1.4 units on a scale
STANDARD_DEVIATION 0.64 • n=5 Participants
|
|
CGI-BP Severity of Illness Score (Mania)
|
1.5 units on a scale
STANDARD_DEVIATION 0.72 • n=5 Participants
|
1.5 units on a scale
STANDARD_DEVIATION 0.72 • n=7 Participants
|
1.5 units on a scale
STANDARD_DEVIATION 0.72 • n=5 Participants
|
|
CGI-BP Severity of Illness Score (Overall)
|
1.6 units on a scale
STANDARD_DEVIATION 0.76 • n=5 Participants
|
1.7 units on a scale
STANDARD_DEVIATION 0.83 • n=7 Participants
|
1.6 units on a scale
STANDARD_DEVIATION 0.79 • n=5 Participants
|
|
Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
|
3.7 units on a scale
STANDARD_DEVIATION 3.45 • n=5 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 3.82 • n=7 Participants
|
3.9 units on a scale
STANDARD_DEVIATION 3.64 • n=5 Participants
|
|
Weight
|
81.3 kg
STANDARD_DEVIATION 25.11 • n=5 Participants
|
80.6 kg
STANDARD_DEVIATION 18.89 • n=7 Participants
|
81.0 kg
STANDARD_DEVIATION 22.20 • n=5 Participants
|
|
Young-Mania Rating Scale (Y-MRS) Total Score
|
4.1 units on a scale
STANDARD_DEVIATION 3.31 • n=5 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 3.56 • n=7 Participants
|
4.1 units on a scale
STANDARD_DEVIATION 3.43 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Randomized Sample; n=number of participants at risk at each time point
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: hospitalization for a manic, mixed or depressive episode; serious adverse event of worsening disease under study accompanied by a Y-MRS \> 16 and/or a MADRS \> 16; discontinuation due to lack of efficacy as determined by the investigator accompanied by a Y-MRS \> 16 and/or a MADRS \> 16.
Outcome measures
| Measure |
Placebo
n=169 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=168 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 0 (n=169, 168)
|
1.00 proportion of participants
|
1.00 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 4 (n=153, 148)
|
0.95 proportion of participants
|
0.96 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 8 (n=148, 139)
|
0.93 proportion of participants
|
0.94 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 12 (n=142, 133)
|
0.90 proportion of participants
|
0.93 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 16 (n=131, 130)
|
0.87 proportion of participants
|
0.92 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 20 (n=122, 128)
|
0.83 proportion of participants
|
0.91 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 24 (n=113, 125)
|
0.81 proportion of participants
|
0.89 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 28 (n=105, 121)
|
0.77 proportion of participants
|
0.89 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 32 (n=102, 114)
|
0.76 proportion of participants
|
0.84 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 36 (n=99, 111)
|
0.75 proportion of participants
|
0.84 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 40 (n=95, 110)
|
0.73 proportion of participants
|
0.84 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 44 (n=91,107)
|
0.73 proportion of participants
|
0.84 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 48 (n=88, 98)
|
0.71 proportion of participants
|
0.83 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse to Any Mood Episode Through Week 52, Phase 3
Proportion at Week 52 (n=5, 8)
|
0.71 proportion of participants
|
0.83 proportion of participants
|
SECONDARY outcome
Timeframe: Baseline (end of Phase 2), 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52Population: LOCF data set, phase 3 efficacy sample; n=number of participants evaluated at given time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 44 (n=164, 162)
|
0.33 units on a scale
Standard Error 0.082
|
0.06 units on a scale
Standard Error 0.080
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Baseline (n=164, 162)
|
1.54 units on a scale
Standard Error 0.059
|
1.54 units on a scale
Standard Error 0.058
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 4 (n=160, 162)
|
0.01 units on a scale
Standard Error 0.052
|
0.05 units on a scale
Standard Error 0.050
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 8 (n=164, 162)
|
0.05 units on a scale
Standard Error 0.054
|
0.01 units on a scale
Standard Error 0.053
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 12 (n=164, 162)
|
0.12 units on a scale
Standard Error 0.063
|
0.07 units on a scale
Standard Error 0.062
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 16 (n=164, 162)
|
0.19 units on a scale
Standard Error 0.064
|
0.07 units on a scale
Standard Error 0.063
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 20 (n=164, 162)
|
0.23 units on a scale
Standard Error 0.071
|
0.07 units on a scale
Standard Error 0.070
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 24 (n=164, 162)
|
0.25 units on a scale
Standard Error 0.074
|
0.05 units on a scale
Standard Error 0.073
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 28 (n=164, 162)
|
0.31 units on a scale
Standard Error 0.082
|
0.10 units on a scale
Standard Error 0.080
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 32 (n=164, 162)
|
0.27 units on a scale
Standard Error 0.078
|
0.08 units on a scale
Standard Error 0.076
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 36 (n=164, 162)
|
0.30 units on a scale
Standard Error 0.079
|
0.05 units on a scale
Standard Error 0.078
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 40 (n=164, 162)
|
0.27 units on a scale
Standard Error 0.080
|
0.05 units on a scale
Standard Error 0.079
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 48 (n=164, 162)
|
0.33 units on a scale
Standard Error 0.082
|
0.05 units on a scale
Standard Error 0.081
|
|
Baseline and Adjusted Mean Change From Baseline in Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) Severity of Illness Score (Mania) Through Phase 3
Mean Change from Baseline to Week 52 (n=164, 162)
|
0.32 units on a scale
Standard Error 0.083
|
0.04 units on a scale
Standard Error 0.082
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3Population: Randomized sample, n=number of participants at risk at given time point
Kaplan-Meier estimated survival rate. Criteria for relapse include one or more of the following: relapse is defined as any of the following events accompanied by a Young-Mania Rating Scale (Y-MRS) \>16 and/or a Montgomery Åsberg Depression Rating Scale (MADRS) \>16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score \>16.
Outcome measures
| Measure |
Placebo
n=169 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=168 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 4 (n=153,148)
|
0.99 proportion of participants
|
0.99 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 8 (n=148,139)
|
0.99 proportion of participants
|
0.98 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 12 (n=142,133)
|
0.97 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 28 (n=105,121)
|
0.90 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 44 (n=91,107)
|
0.86 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 48 (n=88, 98)
|
0.85 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 40 (n=95,110)
|
0.87 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 52 (n=5, 8)
|
0.85 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 0 (n=169,168)
|
1.00 proportion of participants
|
1.00 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 16 (n=132,130)
|
0.95 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 20 (n=122,128)
|
0.93 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 24 (n=113,125)
|
0.91 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 32 (n=102,115)
|
0.89 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Manic Episode Through Phase 3
Proportion at Week 36 (n=99, 111)
|
0.88 proportion of participants
|
0.95 proportion of participants
|
SECONDARY outcome
Timeframe: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of phase 3Population: Randomized sample, n=number of participants at risk at given time point
Kaplan Meier estimated survival rate. Relapse is defined as any of the following events accompanied by a YMRS \> 16 and/or a MADRS \> 16; serious adverse event of worsening disease, or discontinuation by the investigator for lack of efficacy. A hospitalization for a manic, mixed, or depressive episode does meet the criteria for relapse, however does not require an accompanying Y-MRS and/or MADRS score \> 16.
Outcome measures
| Measure |
Placebo
n=169 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=168 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 8 (n=148, 139)
|
0.94 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 12 (n=142, 133)
|
0.94 proportion of participants
|
0.97 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 16 (n=132, 130)
|
0.93 proportion of participants
|
0.96 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 20 (n=123, 128)
|
0.92 proportion of participants
|
0.96 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 24 (n=115, 125)
|
0.92 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 28 (n=107, 121)
|
0.89 proportion of participants
|
0.95 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 32 (n=104, 114)
|
0.89 proportion of participants
|
0.91 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 36 (n=101, 111)
|
0.89 proportion of participants
|
0.91 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 40 (n=98, 110)
|
0.88 proportion of participants
|
0.91 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 48 (n=91, 98)
|
0.87 proportion of participants
|
0.90 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 52 (n=6, 8)
|
0.87 proportion of participants
|
0.90 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 0 (n=169, 168)
|
1.00 proportion of participants
|
1.00 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 4 (n=153, 148)
|
0.96 proportion of participants
|
0.98 proportion of participants
|
|
Proportion of Participants Not Experiencing Relapse of Depressive Episode Through Week 52 During Phase 3
Proportion at Week 44 (n=94, 107)
|
0.88 proportion of participants
|
0.91 proportion of participants
|
SECONDARY outcome
Timeframe: Baseline (end of ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, + Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; n=number of participants with measurement at given time point.
The Y-MRS consists of 11 items: 1) Elevated Mood, 2) Increased Motor Activity -Energy, 3) Sexual Interest, 4) Sleep, 5) Irritability, 6) Speech (Rate and Amount), 7) Language -Thought Disorder, 8) Content, 9) Disruptive-Aggressive Behavior, 10) Appearance, 11) Insight. Seven items are rated on a 0 to 4 scale, while 4 items (items 5, 6, 8 and 9) are rated on a 0 to 8 scale (twice the weight of the other items.) For all items, 0 is the "best" rating and 4 or 8 is the "worst" rating. Total Score is the sum of the ratings for all 11 items. The possible Total Scores are from 0 (best) to 60 (worst).
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=383 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Baseline (n=289, 383)
|
23.15 units on a scale
Standard Error 0.327
|
22.32 units on a scale
Standard Error 0.252
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 1 (n=277, 371)
|
-4.50 units on a scale
Standard Error 0.312
|
-4.86 units on a scale
Standard Error 0.272
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 2 (n=266, 355)
|
-7.90 units on a scale
Standard Error 0.432
|
-7.82 units on a scale
Standard Error 0.351
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 4 (n=245, 326)
|
-12.11 units on a scale
Standard Error 0.454
|
-10.75 units on a scale
Standard Error 0.366
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 6 (n=221, 305)
|
-13.92 units on a scale
Standard Error 0.514
|
-13.28 units on a scale
Standard Error 0.394
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 8 (n=201, 287)
|
-16.18 units on a scale
Standard Error 0.495
|
-14.84 units on a scale
Standard Error 0.406
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 12 (n=179, 253)
|
-17.74 units on a scale
Standard Error 0.528
|
-16.28 units on a scale
Standard Error 0.427
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 16 (n=138, 193)
|
-18.88 units on a scale
Standard Error 0.639
|
-17.55 units on a scale
Standard Error 0.462
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 20 (n=59, 99)
|
-20.37 units on a scale
Standard Error 1.213
|
-17.64 units on a scale
Standard Error 0.741
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Week 24 (n=22, 39)
|
-20.82 units on a scale
Standard Error 1.550
|
-19.77 units on a scale
Standard Error 1.315
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 2
Change from Baseline at Ph2 endpoint (n=289, 383)
|
-14.78 units on a scale
Standard Error 0.530
|
-14.32 units on a scale
Standard Error 0.429
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 of Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; n=number of participants with measurement at time point
The Y-MRS consists of 11 items: 1) Elevated Mood, 2) Increased Motor Activity -Energy, 3) Sexual Interest, 4) Sleep, 5) Irritability, 6) Speech (Rate and Amount), 7) Language -Thought Disorder, 8) Content, 9) Disruptive-Aggressive Behavior, 10) Appearance, 11) Insight. 7 items are rated on a 0 to 4 scale, while 4 items (items 5, 6, 8 and 9) are rated on a 0 to 8 scale (twice the weight of the other items.) For all items, 0 is the "best" rating and 4 or 8 is the "worst" rating. Total Score is the sum of the ratings for all 11 items. The possible Total Scores are from 0 (best) to 60 (worst).
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Baseline (n=164, 162)
|
4.03 units on a scale
Standard Error 0.285
|
4.06 units on a scale
Standard Error 0.280
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 4 (n=160, 162)
|
0.47 units on a scale
Standard Error 0.342
|
0.53 units on a scale
Standard Error 0.332
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 8 (n=164, 162)
|
0.91 units on a scale
Standard Error 0.353
|
0.23 units on a scale
Standard Error 0.346
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 20 (n=164, 162)
|
2.29 units on a scale
Standard Error 0.472
|
0.38 units on a scale
Standard Error 0.463
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 24 (n=164, 162)
|
2.42 units on a scale
Standard Error 0.492
|
0.24 units on a scale
Standard Error 0.483
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 28 (n=164, 162)
|
3.02 units on a scale
Standard Error 0.547
|
0.40 units on a scale
Standard Error 0.537
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 32 (n=164, 162)
|
2.72 units on a scale
Standard Error 0.526
|
0.39 units on a scale
Standard Error 0.516
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 48 (n=164, 162)
|
3.15 units on a scale
Standard Error 0.575
|
0.07 units on a scale
Standard Error 0.564
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 52 (n=164, 162)
|
2.93 units on a scale
Standard Error 0.576
|
-0.11 units on a scale
Standard Error 0.565
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 36 (n=164, 162)
|
3.04 units on a scale
Standard Error 0.538
|
0.26 units on a scale
Standard Error 0.528
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 40 (n=164, 162)
|
2.82 units on a scale
Standard Error 0.542
|
0.11 units on a scale
Standard Error 0.532
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 44 (n=164, 162)
|
3.19 units on a scale
Standard Error 0.558
|
0.27 units on a scale
Standard Error 0.548
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 12 (n=164, 162)
|
1.53 units on a scale
Standard Error 0.415
|
0.43 units on a scale
Standard Error 0.408
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Young-Mania Rating Scale (Y-MRS) Total Score Through Phase 3
Change at Week 16 (n=164, 162)
|
1.74 units on a scale
Standard Error 0.433
|
0.35 units on a scale
Standard Error 0.425
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 (Ph2) Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=383 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 1 (n=277, 371)
|
-1.48 units on a scale
Standard Error 0.295
|
-1.51 units on a scale
Standard Error 0.256
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 2 (n=267, 355)
|
-2.23 units on a scale
Standard Error 0.352
|
-2.70 units on a scale
Standard Error 0.329
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 4 (n=245, 326)
|
-2.94 units on a scale
Standard Error 0.391
|
-3.16 units on a scale
Standard Error 0.357
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Mean Baseline (n=289, 383)
|
10.97 units on a scale
Standard Error 0.508
|
11.56 units on a scale
Standard Error 0.432
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 6 (n=221, 305)
|
-2.92 units on a scale
Standard Error 0.466
|
-3.69 units on a scale
Standard Error 0.383
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 8 (n=201, 287)
|
-3.07 units on a scale
Standard Error 0.460
|
-3.64 units on a scale
Standard Error 0.440
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 12 (n=179, 253)
|
-2.82 units on a scale
Standard Error 0.500
|
-3.91 units on a scale
Standard Error 0.398
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 16 (n=138, 193)
|
-2.88 units on a scale
Standard Error 0.698
|
-4.28 units on a scale
Standard Error 0.425
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 20 (n=59, 99)
|
-4.68 units on a scale
Standard Error 0.944
|
-4.49 units on a scale
Standard Error 0.676
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Week 24 (n=22, 39)
|
-3.77 units on a scale
Standard Error 1.298
|
-5.15 units on a scale
Standard Error 1.186
|
|
Mean Baseline and Unadjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 2 and at Phase 2 Endpoint
Change from Baseline at Ph2 Endpoint (n=289, 383)
|
-2.13 units on a scale
Standard Error 0.461
|
-2.54 units on a scale
Standard Error 0.412
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; N=number of participants evaluated at time point; 4 participants in the Week 4 placebo group were not evaluated.
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 4 (n=160, 162)
|
1.92 units on a scale
Standard Error 0.421
|
1.42 units on a scale
Standard Error 0.411
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 8 (n=164, 162)
|
2.27 units on a scale
Standard Error 0.495
|
1.23 units on a scale
Standard Error 0.488
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 32 (n=164, 162)
|
3.32 units on a scale
Standard Error 0.609
|
1.70 units on a scale
Standard Error 0.601
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 36 (n=164, 162)
|
3.03 units on a scale
Standard Error 0.621
|
1.89 units on a scale
Standard Error 0.612
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 40 (n=164, 162)
|
3.18 units on a scale
Standard Error 0.626
|
1.65 units on a scale
Standard Error 0.618
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 44 (n=164, 162)
|
3.10 units on a scale
Standard Error 0.641
|
1.53 units on a scale
Standard Error 0.632
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 52 (n=164, 162)
|
3.47 units on a scale
Standard Error 0.640
|
1.46 units on a scale
Standard Error 0.632
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Baseline (n=164, 162)
|
4.41 units on a scale
Standard Error 0.282
|
4.62 units on a scale
Standard Error 0.277
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 12 (n=164, 162)
|
2.42 units on a scale
Standard Error 0.493
|
1.42 units on a scale
Standard Error 0.486
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 16 (n=164, 162)
|
2.12 units on a scale
Standard Error 0.505
|
1.27 units on a scale
Standard Error 0.498
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 20 (n=164, 162)
|
2.61 units on a scale
Standard Error 0.557
|
1.47 units on a scale
Standard Error 0.549
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 24 (n=164, 162)
|
2.92 units on a scale
Standard Error 0.572
|
1.49 units on a scale
Standard Error 0.564
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 28 (n=164, 162)
|
3.14 units on a scale
Standard Error 0.601
|
1.64 units on a scale
Standard Error 0.594
|
|
Mean Baseline and Adjusted Mean Change From Baseline in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score Through Phase 3
Mean Change from Baseline at Week 48 (n=164, 162)
|
3.57 units on a scale
Standard Error 0.633
|
1.48 units on a scale
Standard Error 0.624
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=383 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Baseline (BL) (n=289, 383)
|
4.25 units on a scale
Standard Error 0.040
|
4.08 units on a scale
Standard Error 0.036
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 4 (n=245, 326)
|
-1.56 units on a scale
Standard Error 0.074
|
-1.31 units on a scale
Standard Error 0.059
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
-1.86 units on a scale
Standard Error 0.084
|
-1.62 units on a scale
Standard Error 0.063
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
-2.57 units on a scale
Standard Error 0.106
|
-2.17 units on a scale
Standard Error 0.079
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
-2.71 units on a scale
Standard Error 0.181
|
-2.14 units on a scale
Standard Error 0.118
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,383)
|
-1.90 units on a scale
Standard Error 0.085
|
-1.66 units on a scale
Standard Error 0.070
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 1 (n=275, 370)
|
-0.52 units on a scale
Standard Error 0.046
|
-0.53 units on a scale
Standard Error 0.040
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 2 (n=267, 354)
|
-1.05 units on a scale
Standard Error 0.061
|
-0.97 units on a scale
Standard Error 0.054
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
-2.17 units on a scale
Standard Error 0.081
|
-1.80 units on a scale
Standard Error 0.069
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 12 (n=179, 252)
|
-2.31 units on a scale
Standard Error 0.097
|
-1.99 units on a scale
Standard Error 0.078
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
-2.73 units on a scale
Standard Error 0.220
|
-2.38 units on a scale
Standard Error 0.186
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Baseline
|
1.65 units on a scale
Standard Error 0.065
|
1.70 units on a scale
Standard Error 0.064
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 4 (n=160, 162)
|
0.25 units on a scale
Standard Error 0.072
|
0.27 units on a scale
Standard Error 0.070
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 8
|
0.32 units on a scale
Standard Error 0.080
|
0.21 units on a scale
Standard Error 0.079
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 12
|
0.40 units on a scale
Standard Error 0.087
|
0.26 units on a scale
Standard Error 0.085
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 16
|
0.44 units on a scale
Standard Error 0.088
|
0.26 units on a scale
Standard Error 0.087
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 20
|
0.51 units on a scale
Standard Error 0.095
|
0.29 units on a scale
Standard Error 0.094
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 24
|
0.56 units on a scale
Standard Error 0.097
|
0.25 units on a scale
Standard Error 0.095
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 28
|
0.62 units on a scale
Standard Error 0.101
|
0.32 units on a scale
Standard Error 0.099
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 32
|
0.61 units on a scale
Standard Error 0.102
|
0.30 units on a scale
Standard Error 0.100
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 36
|
0.62 units on a scale
Standard Error 0.103
|
0.33 units on a scale
Standard Error 0.101
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 40
|
0.57 units on a scale
Standard Error 0.104
|
0.28 units on a scale
Standard Error 0.102
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 44
|
0.64 units on a scale
Standard Error 0.105
|
0.30 units on a scale
Standard Error 0.103
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 48
|
0.68 units on a scale
Standard Error 0.106
|
0.28 units on a scale
Standard Error 0.104
|
|
Baseline and Adjusted Mean Change From Baseline in the CGI-BP Severity of Illness (Overall) Through Phase 3
Mean Change from Baseline At Week 52
|
0.66 units on a scale
Standard Error 0.106
|
0.31 units on a scale
Standard Error 0.104
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=383 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Baseline (BL) (n=289, 383)
|
2.16 units on a scale
Standard Error 0.076
|
2.33 units on a scale
Standard Error 0.069
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 1 (n=275, 370)
|
-0.16 units on a scale
Standard Error 0.041
|
-0.19 units on a scale
Standard Error 0.040
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 2 (n=267, 354)
|
-0.22 units on a scale
Standard Error 0.053
|
-0.33 units on a scale
Standard Error 0.050
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 4 (n=245, 326)
|
-0.29 units on a scale
Standard Error 0.058
|
-0.39 units on a scale
Standard Error 0.055
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
-0.31 units on a scale
Standard Error 0.068
|
-0.43 units on a scale
Standard Error 0.061
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
-0.30 units on a scale
Standard Error 0.077
|
-0.37 units on a scale
Standard Error 0.066
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 12 (n=179, 252)
|
-0.17 units on a scale
Standard Error 0.077
|
-0.35 units on a scale
Standard Error 0.069
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
-0.21 units on a scale
Standard Error 0.109
|
-0.36 units on a scale
Standard Error 0.078
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
-0.27 units on a scale
Standard Error 0.149
|
-0.37 units on a scale
Standard Error 0.116
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
-0.23 units on a scale
Standard Error 0.227
|
-0.46 units on a scale
Standard Error 0.217
|
|
Unadjusted Mean Change Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Depression) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,383)
|
-0.16 units on a scale
Standard Error 0.069
|
-0.26 units on a scale
Standard Error 0.063
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 2), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 40
|
0.47 units on a scale
Standard Error 0.093
|
0.28 units on a scale
Standard Error 0.091
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 44
|
0.46 units on a scale
Standard Error 0.094
|
0.28 units on a scale
Standard Error 0.093
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Baseline Mean
|
1.43 units on a scale
Standard Error 0.049
|
1.47 units on a scale
Standard Error 0.048
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 4 (n=160, 162)
|
0.30 units on a scale
Standard Error 0.067
|
0.29 units on a scale
Standard Error 0.065
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 8
|
0.35 units on a scale
Standard Error 0.073
|
0.24 units on a scale
Standard Error 0.072
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 12
|
0.37 units on a scale
Standard Error 0.077
|
0.23 units on a scale
Standard Error 0.076
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 16
|
0.35 units on a scale
Standard Error 0.078
|
0.24 units on a scale
Standard Error 0.077
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 20
|
0.41 units on a scale
Standard Error 0.084
|
0.28 units on a scale
Standard Error 0.083
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 24
|
0.44 units on a scale
Standard Error 0.086
|
0.27 units on a scale
Standard Error 0.085
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 28
|
0.50 units on a scale
Standard Error 0.091
|
0.28 units on a scale
Standard Error 0.090
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 32
|
0.53 units on a scale
Standard Error 0.092
|
0.27 units on a scale
Standard Error 0.091
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 36
|
0.49 units on a scale
Standard Error 0.092
|
0.32 units on a scale
Standard Error 0.091
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 48
|
0.50 units on a scale
Standard Error 0.094
|
0.27 units on a scale
Standard Error 0.092
|
|
Baseline and Adjusted Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Score Through Phase 3
Mean Change from Baseline at Week 52
|
0.51 units on a scale
Standard Error 0.094
|
0.30 units on a scale
Standard Error 0.093
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall change from preceding phase items on a 7-point scale \[1 to 7\], with 1 being very much improved and 7 being very much worse).
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=382 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 1 (n=274, 369)
|
3.15 units on a scale
Standard Error 0.055
|
3.09 units on a scale
Standard Error 0.049
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 2 (n=265, 353)
|
2.61 units on a scale
Standard Error 0.062
|
2.58 units on a scale
Standard Error 0.054
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
1.54 units on a scale
Standard Error 0.082
|
1.61 units on a scale
Standard Error 0.056
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
1.69 units on a scale
Standard Error 0.161
|
1.68 units on a scale
Standard Error 0.087
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
1.64 units on a scale
Standard Error 0.214
|
1.67 units on a scale
Standard Error 0.181
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,382)
|
1.95 units on a scale
Standard Error 0.071
|
1.94 units on a scale
Standard Error 0.056
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 4 (n=245, 325)
|
2.14 units on a scale
Standard Error 0.060
|
2.24 units on a scale
Standard Error 0.056
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
1.95 units on a scale
Standard Error 0.065
|
1.97 units on a scale
Standard Error 0.056
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
1.73 units on a scale
Standard Error 0.062
|
1.80 units on a scale
Standard Error 0.055
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Mania) Through Phase 2
Mean Change from BL to Week 12 (n=179, 252)
|
1.66 units on a scale
Standard Error 0.074
|
1.65 units on a scale
Standard Error 0.053
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Weeks 1, 2, 4,6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from baseline (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=383 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 2 (n=267, 354)
|
-1.15 units on a scale
Standard Error 0.064
|
-1.06 units on a scale
Standard Error 0.055
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 1 (n=275, 370)
|
-0.58 units on a scale
Standard Error 0.047
|
-0.58 units on a scale
Standard Error 0.042
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
-2.93 units on a scale
Standard Error 0.162
|
-2.32 units on a scale
Standard Error 0.115
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Baseline (BL) (n=289, 383)
|
4.22 units on a scale
Standard Error 0.040
|
4.06 units on a scale
Standard Error 0.035
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 4 (n=245, 326)
|
-1.73 units on a scale
Standard Error 0.075
|
-1.45 units on a scale
Standard Error 0.062
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
-2.04 units on a scale
Standard Error 0.081
|
-1.82 units on a scale
Standard Error 0.065
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
-2.40 units on a scale
Standard Error 0.076
|
-2.06 units on a scale
Standard Error 0.067
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 12 (n=179, 252)
|
-2.60 units on a scale
Standard Error 0.081
|
-2.27 units on a scale
Standard Error 0.071
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
-2.83 units on a scale
Standard Error 0.086
|
-2.40 units on a scale
Standard Error 0.075
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
-2.91 units on a scale
Standard Error 0.185
|
-2.56 units on a scale
Standard Error 0.163
|
|
Unadjusted Mean Baseline and Mean Change From Baseline in the CGI-BP Severity of Illness (Mania) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,383)
|
-2.21 units on a scale
Standard Error 0.079
|
-2.01 units on a scale
Standard Error 0.066
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 4 (n=160, 162)
|
2.96 units on a scale
Standard Error 0.111
|
3.00 units on a scale
Standard Error 0.108
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 52
|
3.29 units on a scale
Standard Error 0.131
|
2.89 units on a scale
Standard Error 0.129
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 8
|
3.17 units on a scale
Standard Error 0.113
|
2.98 units on a scale
Standard Error 0.111
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 12
|
3.14 units on a scale
Standard Error 0.118
|
3.03 units on a scale
Standard Error 0.116
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 16
|
3.27 units on a scale
Standard Error 0.118
|
2.98 units on a scale
Standard Error 0.115
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 20
|
3.29 units on a scale
Standard Error 0.120
|
3.03 units on a scale
Standard Error 0.118
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 24
|
3.26 units on a scale
Standard Error 0.125
|
2.96 units on a scale
Standard Error 0.123
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 28
|
3.37 units on a scale
Standard Error 0.126
|
3.01 units on a scale
Standard Error 0.124
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 32
|
3.31 units on a scale
Standard Error 0.124
|
3.00 units on a scale
Standard Error 0.122
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 36
|
3.37 units on a scale
Standard Error 0.125
|
2.94 units on a scale
Standard Error 0.123
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 40
|
3.32 units on a scale
Standard Error 0.126
|
2.94 units on a scale
Standard Error 0.124
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 44
|
3.33 units on a scale
Standard Error 0.128
|
2.96 units on a scale
Standard Error 0.125
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Mania) Through Phase 3
Mean Change at Week 48
|
3.35 units on a scale
Standard Error 0.130
|
2.96 units on a scale
Standard Error 0.128
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being very much improved and 7 being very much worse).
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=382 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,382)
|
3.30 units on a scale
Standard Error 0.080
|
3.26 units on a scale
Standard Error 0.075
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 1 (n=274, 368)
|
3.56 units on a scale
Standard Error 0.054
|
3.40 units on a scale
Standard Error 0.057
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 2 (n=265, 353)
|
3.42 units on a scale
Standard Error 0.061
|
3.25 units on a scale
Standard Error 0.066
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 4 (n=245, 325)
|
3.35 units on a scale
Standard Error 0.074
|
3.19 units on a scale
Standard Error 0.071
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
3.22 units on a scale
Standard Error 0.083
|
3.13 units on a scale
Standard Error 0.078
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
3.13 units on a scale
Standard Error 0.090
|
3.11 units on a scale
Standard Error 0.084
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 12 (n=179, 250)
|
3.28 units on a scale
Standard Error 0.094
|
3.06 units on a scale
Standard Error 0.087
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
3.30 units on a scale
Standard Error 0.117
|
2.99 units on a scale
Standard Error 0.100
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
3.24 units on a scale
Standard Error 0.173
|
3.18 units on a scale
Standard Error 0.129
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Depression) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
2.91 units on a scale
Standard Error 0.278
|
3.15 units on a scale
Standard Error 0.251
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being very much improved and 7 being very much worse).
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 4 (n=160, 162)
|
3.46 units on a scale
Standard Error 0.102
|
3.56 units on a scale
Standard Error 0.100
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 40
|
3.55 units on a scale
Standard Error 0.120
|
3.47 units on a scale
Standard Error 0.118
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 8
|
3.55 units on a scale
Standard Error 0.103
|
3.52 units on a scale
Standard Error 0.101
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 12
|
3.51 units on a scale
Standard Error 0.106
|
3.45 units on a scale
Standard Error 0.104
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 16
|
3.52 units on a scale
Standard Error 0.108
|
3.45 units on a scale
Standard Error 0.107
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 20
|
3.58 units on a scale
Standard Error 0.111
|
3.53 units on a scale
Standard Error 0.109
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 24
|
3.63 units on a scale
Standard Error 0.112
|
3.54 units on a scale
Standard Error 0.110
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 28
|
3.65 units on a scale
Standard Error 0.116
|
3.52 units on a scale
Standard Error 0.114
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 32
|
3.69 units on a scale
Standard Error 0.116
|
3.49 units on a scale
Standard Error 0.114
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 36
|
3.62 units on a scale
Standard Error 0.119
|
3.52 units on a scale
Standard Error 0.117
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 44
|
3.52 units on a scale
Standard Error 0.121
|
3.49 units on a scale
Standard Error 0.120
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 48
|
3.58 units on a scale
Standard Error 0.121
|
3.44 units on a scale
Standard Error 0.120
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Depression) Through Phase 3
Mean Change at Week 52
|
3.56 units on a scale
Standard Error 0.122
|
3.44 units on a scale
Standard Error 0.120
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, and Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Observed Cases (OC) data set; phase 2 endpoint was phase 2 efficacy sample. n=number of participants with evaluation at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being very much improved and 7 being very much worse).
Outcome measures
| Measure |
Placebo
n=289 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=382 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 12 (n=179, 252)
|
1.87 units on a scale
Standard Error 0.081
|
1.94 units on a scale
Standard Error 0.071
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 16 (n=138, 193)
|
1.74 units on a scale
Standard Error 0.096
|
1.80 units on a scale
Standard Error 0.069
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 1 (n=274, 369)
|
3.20 units on a scale
Standard Error 0.054
|
3.13 units on a scale
Standard Error 0.048
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 2 (n=265, 353)
|
2.70 units on a scale
Standard Error 0.063
|
2.69 units on a scale
Standard Error 0.057
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 4 (n=245, 325)
|
2.27 units on a scale
Standard Error 0.063
|
2.40 units on a scale
Standard Error 0.060
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 6 (n=219, 305)
|
2.11 units on a scale
Standard Error 0.069
|
2.19 units on a scale
Standard Error 0.064
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 8 (n=200, 287)
|
1.94 units on a scale
Standard Error 0.073
|
2.08 units on a scale
Standard Error 0.070
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 20 (n=59, 99)
|
1.81 units on a scale
Standard Error 0.156
|
1.90 units on a scale
Standard Error 0.112
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Week 24 (n=22, 39)
|
1.68 units on a scale
Standard Error 0.212
|
1.82 units on a scale
Standard Error 0.226
|
|
Unadjusted Mean Change From Preceding Phase in the CGI-BP (Overall) Through Phase 2
Mean Change from BL to Phase 2 Endpoint(n=289,382)
|
2.26 units on a scale
Standard Error 0.082
|
2.37 units on a scale
Standard Error 0.072
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: LOCF data set, phase 3 efficacy sample; 4 participants in the Week 4 placebo group were not evaluated.
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change from baseline (in this case, preceding phase) in patients with bipolar disorder. Patients are rated on mania, depression and overall bipolar illness items on a 7-point scale \[1 to 7\], with 1 being very much improved and 7 being very much worse).
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 12
|
3.34 units on a scale
Standard Error 0.122
|
3.27 units on a scale
Standard Error 0.120
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 20
|
3.53 units on a scale
Standard Error 0.125
|
3.31 units on a scale
Standard Error 0.122
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 44
|
3.57 units on a scale
Standard Error 0.135
|
3.28 units on a scale
Standard Error 0.132
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 4 (n=160, 162)
|
3.17 units on a scale
Standard Error 0.113
|
3.27 units on a scale
Standard Error 0.110
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 8
|
3.36 units on a scale
Standard Error 0.118
|
3.22 units on a scale
Standard Error 0.116
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 16
|
3.45 units on a scale
Standard Error 0.121
|
3.22 units on a scale
Standard Error 0.119
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 24
|
3.60 units on a scale
Standard Error 0.127
|
3.31 units on a scale
Standard Error 0.125
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 28
|
3.65 units on a scale
Standard Error 0.130
|
3.31 units on a scale
Standard Error 0.127
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 32
|
3.63 units on a scale
Standard Error 0.130
|
3.29 units on a scale
Standard Error 0.128
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 36
|
3.61 units on a scale
Standard Error 0.132
|
3.28 units on a scale
Standard Error 0.130
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 40
|
3.54 units on a scale
Standard Error 0.133
|
3.24 units on a scale
Standard Error 0.131
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 48
|
3.63 units on a scale
Standard Error 0.136
|
3.26 units on a scale
Standard Error 0.134
|
|
Adjusted Mean Change in CGI-BP From Preceding Phase (Overall) Through Phase 3
Mean Change at Week 52
|
3.58 units on a scale
Standard Error 0.138
|
3.25 units on a scale
Standard Error 0.135
|
SECONDARY outcome
Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Observed cases data set, Phase 3 Efficacy Sample
Remission is defined as Y-MRS Total Score \<=12 and MADRS Total Score \<=12.
Outcome measures
| Measure |
Placebo
n=160 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants Maintaining Remission During Phase 3
Week 4 (n=160, 162)
|
142 participants
|
142 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 20 (n=131, 127)
|
115 participants
|
117 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 52 (n=89, 97)
|
82 participants
|
95 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 8 (n=152, 145)
|
138 participants
|
136 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 12 (n=144, 136)
|
133 participants
|
126 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 16 (n=138, 131)
|
122 participants
|
126 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 24 (n=115, 122)
|
107 participants
|
119 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 28 (n=114, 122)
|
100 participants
|
115 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 32 (n=104, 119)
|
99 participants
|
112 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 36 (n=99, 108)
|
91 participants
|
104 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 40 (n=100, 110)
|
93 participants
|
109 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 44 (n=91, 109)
|
81 participants
|
102 participants
|
|
Number of Participants Maintaining Remission During Phase 3
Week 48 (n=92, 102)
|
85 participants
|
101 participants
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Randomized Sample
Outcome measures
| Measure |
Placebo
n=169 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=168 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Proportion of Participants Discontinuing For Any Reason Through Week 52 (During Phase 3)
|
0.473 Proportion of Participants
|
0.387 Proportion of Participants
|
SECONDARY outcome
Timeframe: During Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Outcome measures
| Measure |
Placebo
n=292 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=390 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
SAEs
|
5 Participants
|
10 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Deaths
|
0 Participants
|
0 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Discontinuations due to AEs
|
38 Participants
|
50 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Any AE
|
226 Participants
|
287 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Treatment-related AEs in >=2% of Participants
|
188 Participants
|
233 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs During Phase 2
Any Extrapyramidal Syndrome-Related AE
|
108 Participants
|
113 Participants
|
SECONDARY outcome
Timeframe: During Phase 2. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Outcome measures
| Measure |
Placebo
n=292 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=390 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Severe/Grade 3
|
20 Participants
|
31 Participants
|
|
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Any Adverse Event
|
226 Participants
|
287 Participants
|
|
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Mild/Grade 1
|
172 Participants
|
219 Participants
|
|
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Moderate/Grade 2
|
109 Participants
|
165 Participants
|
|
Treatment-Emergent Adverse Events in >=5 Percent of Participants, by Severity, During Phase 2
Very Severe/Grade 4
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample
Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate \<100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
Outcome measures
| Measure |
Placebo
n=292 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=390 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Ventricular Premature Beat - not present → present
|
2 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Atrial Flutter not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
2nd Degree AV Block not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTc Frederica (QTcF) > 450 msec
|
5 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcF Change from Baseline > 30 msec
|
21 Participants
|
11 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcB Change from Baseline > 60 msec
|
2 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcF Change from Baseline > 60 msec
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Sinus Bradycardia (see description)
|
0 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Tachycardia ≥ 120 bpm and ↑ ≥ 15 bpm
|
0 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Bradycardia ≤ 50 bpm and ↓ 15 bpm
|
0 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Sinus Tachycardia (see description)
|
0 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
SV Premature Beat - not present → present
|
2 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
SV Tachycardia not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Ventricular Tachycardia not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Atrial Fibrillation (see description)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
1st Degree AV Block PR ≥0.20 sec and ↑ ≥0.05 sec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
3rd Degree AV Block not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Left Bundle Branch Block not present → present
|
11 Participants
|
7 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Right Bundle Branch Block not present → present
|
5 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Pre-excitation Syndrome not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Other Intraventricular Block (see description)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Acute Infarction not present → present
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Subacute (Recent) Infarction not present → present
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Old Infarction not present → present at >=12 weeks
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Myocardial Ischemia not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
Symmetrical T-Wave Inversion not present → present
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTc Bazett (QTcB) > 450 msec
|
15 Participants
|
8 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcB > 500 msec
|
2 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcF > 500 msec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 2
QTcB Change from Baseline > 30 msec
|
28 Participants
|
17 Participants
|
SECONDARY outcome
Timeframe: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample
Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
Outcome measures
| Measure |
Placebo
n=292 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=390 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Systolic Blood Pressure (SBP) - Standing Increase
|
2 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
SBP - Sitting Increase
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
SBP - Standing Decrease
|
0 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
SBP - Supine Increase
|
1 Participants
|
6 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
SBP - Supine Decrease
|
2 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
SBP - Sitting Decrease
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Diastolic Blood Pressure (DBP) - Standing Increase
|
4 Participants
|
7 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
DBP - Standing Decrease
|
0 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
DBP - Supine Increase
|
2 Participants
|
5 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
DBP - Supine Decrease
|
1 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
DBP - Sitting Increase
|
0 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
DBP - Sitting Decrease
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Standing Increase
|
0 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Standing Decrease
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Supine Increase
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Supine Decrease
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Sitting Increase
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Heart Rate - Sitting Decrease
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Weight - Increase
|
26 Participants
|
46 Participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 2
Weight - Decrease
|
15 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n=number of participants with evaluation at time point
ULN=upper limit of normal; HDL=high density lipoprotein; LDL=low density lipoprotein. Values for ULN are provided by the lab in the database and could be different for each individual patient based on characteristics such as age, gender, or other patient attributes.
Outcome measures
| Measure |
Placebo
n=292 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=390 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Alkaline Phosphatase ≥ 3 x ULN (n=272, 360)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Platelets ≤75,000 mm^3/≥700,000 mm^3 (n=268, 357)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
HDL Cholesterol (Fasting) <40 mg/dL (n=252, 332)
|
85 Participants
|
117 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Alanine Aminotransferase ≥ 3 x ULN (n=273, 359)
|
3 Participants
|
6 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Aspartate Aminotransferase ≥ 3 x ULN (n=273, 359)
|
0 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Blood Urea Nitrogen ≥ 30 mg/dL (n=225, 312)
|
0 Participants
|
7 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Creatine Kinase >= 3 x ULN (n=273, 360)
|
6 Participants
|
20 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Creatinine ≥ 2.0 mg/dL (n=271, 359)
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Lactate Dehydrogenase >= 3 x ULN (n=270, 358)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Prolactin > ULN (n=231, 306)
|
10 Participants
|
9 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Bilirubin Total ≥ 2.0 mg/dL (n=n=272, 360)
|
2 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Uric Acid ≥10.5mg/dL(M)/≥8.5mg/dL(F) (n=273, 360)
|
10 Participants
|
7 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Total Calcium ≤8.2 mg/dL or ≥12 mg/dL (n=273, 360)
|
2 Participants
|
13 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Chloride Serum ≤90 mEq/L or ≥118 mEq/L(n=273, 360)
|
1 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Potassium Serum ≤2.5 mEq/L/≥6.5 mEq/L(n=271, 358)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Sodium Serum ≤126 mEq/L/≥156 mEq/L (n=273, 360)
|
0 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Hematocrit ≤37(M)/≤32(F)+3 pts↓from BL(n=272, 358)
|
5 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Hemoglobin ≤11.5 g/dL(M)/≤9.5 g/dL(F) (n=272, 359)
|
8 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Leukocytes <=2800 mm^3 or >=16000 mm^3(n=272, 358)
|
9 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Eosinophils Relative (Calculated) ≥10%(n=272, 358)
|
9 Participants
|
12 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Neutrophils Relative (Calculated) ≤15%(n=272, 358)
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Urine Glucose-any glucose in the urine(n=269,357)
|
7 Participants
|
13 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Urine Protein Increase of ≥ 2 units (n=269, 357)
|
10 Participants
|
6 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Glucose (Non-fasting) ≥200 mg/dL (n=78, 89)
|
2 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Glucose (Fasting) ≥ 126 mg/dL (n=251, 332)
|
42 Participants
|
28 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
HDL Cholesterol (combined) <40 mg/dL (n=273, 360)
|
94 Participants
|
131 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
HDL Cholesterol (Non-fasting) <40 mg/dL (n=79, 91)
|
20 Participants
|
31 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Total Cholesterol (Combined) ≥240 mg/dL(n=273,360)
|
37 Participants
|
53 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Total Cholesterol (Fasting) ≥240 mg/dL (n=252,332)
|
32 Participants
|
49 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Total Cholesterol (Non-fasting) ≥240mg/dL(n=79,92)
|
7 Participants
|
11 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
LDL Cholesterol (Combined) ≥160 mg/dL (n=273, 360)
|
30 Participants
|
47 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
LDL Cholesterol (Fasting) ≥160 mg/dL (n=252, 332)
|
28 Participants
|
44 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
LDL Cholesterol (Non-fasting) ≥160 mg/dL (n=79,91)
|
4 Participants
|
8 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Triglycerides (Combined) ≥ 200 mg/dL (n=273, 360)
|
88 Participants
|
108 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Triglycerides (Non-Fasting) ≥ 200 mg/dL (n=79, 93)
|
25 Participants
|
33 Participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 2
Triglycerides (Fasting) ≥ 200 mg/dL (n=252, 332)
|
73 Participants
|
85 Participants
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n= participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=223 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=285 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
RR Change at Phase 2 Endpoint (n=223, 284)
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QTcBazett (QTcB) at Baseline (n=223, 285)
|
415.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
412.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QTcB Change at Phase 2 Endpoint (n=223, 285)
|
4.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-8.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QTcB (0.33) at Baseline (n=223, 284)
|
403.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
400.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QTcB(0.33) Change at Phase 2 Endpoint (n=223, 284)
|
4.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
PR at Baseline (n=222, 284)
|
154.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
150.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
PR Change at Phase 2 Endpoint (n=222, 284)
|
2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
RR at Baseline (n=223, 284)
|
845.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
870.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QRS at Baseline (n=223, 284)
|
90.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
90.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in ECG Measurements During Phase 2
QRS Change at Phase 2 Endpoint (n=223, 284)
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n= participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=286 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=372 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Supine Heart Rate (HR) at Baseline (n=286, 372)
|
76.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
74.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Supine HR Change at Phase 2 Endpoint (n=286, 372)
|
0.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Sitting Heart Rate (HR) at Baseline (n=51, 67)
|
78.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
82.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Sitting HR Change at Phase 2 Endpoint (n=51, 67)
|
2.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Standing HR at Baseline (n=260, 333)
|
78.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
78.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Vital Sign Measurements During Phase 2
Standing HR Change at Phase 2 Endpoint(n=260, 333)
|
0.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n= participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=286 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=372 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Standing DBP at Baseline (n=260, 333)
|
78.5 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
78.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Supine Systolic BP (SBP) at Baseline (n=286, 372)
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Supine SBP Change at Phase 2 Endpoint (n=286, 372)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Supine Diastolic BP (DBP) at Baseline(n=286, 372)
|
76.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
77.5 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Supine DBP Change at Phase 2 Endpoint (n=286, 372)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Sitting SBP at Baseline (n=51, 67)
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Sitting SBP Change at Phase 2 Endpoint (n=51, 67)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Sitting DBP at Baseline (n=51, 67)
|
78.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
80.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Sitting DBP Change at Phase 2 Endpoint (n=51, 67)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Standing SBP at Baseline (n=260, 333)
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Standing SBP Change at Phase 2 Endpoint(n=260,333)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Blood Pressure (BP) Vital Sign Measurements During Phase 2
Standing DBP Change at Phase 2 Endpoint(n=260,333)
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mmHg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=218 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=294 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
Weight at Baseline
|
76.2 kg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
76.4 kg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Weight Vital Sign Measurements At Phase 2 Endpoint
Weight Change at Phase 2 Endpoint
|
0.9 kg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.5 kg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=218 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=294 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
BMI at Baseline
|
26.9 kg/m^2
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
27.2 kg/m^2
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) Vital Sign Measurements at Phase 2 Endpoint
BMI Change at Phase 2 Endpoint
|
0.3 kg/m^2
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.5 kg/m^2
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
ALP (n=265, 347)
|
72.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
64.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
ALT (n=266, 346)
|
20.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
17.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
AST (n=266, 346)
|
19.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
20.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
CK (n=266, 347)
|
79.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
91.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD), Phase 2 Safety Sample
LD (n=262, 342)
|
168.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
173.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
ALP (n=265, 347)
|
-2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
ALT (n=266, 346)
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
AST (n=266, 346)
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
CK (n=266, 347)
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Lactate Dehydrogenase (LD) at the End of Phase 2
LD (n=262, 342)
|
-3.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 (a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n= participants with measurement at time point.
Outcome measures
| Measure |
Placebo
n=223 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=285 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
Heart Rate at Baseline (n=223, 284)
|
71.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
69.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline and Change From Baseline in Heart Rate Measurements During Phase 2
Heart Rate Change at Phase 2 Endpoint (n=223, 284)
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Bilirubin (n=265, 347)
|
0.40 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.40 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Uric Acid (n=266, 347)
|
5.55 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
5.10 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
BUN (n=223, 302)
|
11.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
13.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
TC (n=245, 318)
|
182.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
174.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Creatine (n=263, 343)
|
0.900 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.900 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Glucose (n=242, 312)
|
92.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
89.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
HDL-C (n=245, 318)
|
47.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
45.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
LDL-C (n=245, 318)
|
105.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
101.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Blood Urea Nitrogen (BUN), Total Cholesterol-Fasting (TC), Creatine, Glucose, High Density Lipoprotein Cholesterol-Fasting (HDL-C), Low Density Lipoprotein Cholesterol-Fasting (LDL-C), Bilirubin-Total, Triglycerides, and Uric Acid
Triglycerides (n=245, 318)
|
112.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
114.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Bilirubin (n=265, 347)
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Triglycerides (n=245, 318)
|
2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
3.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
BUN (n=223, 302)
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
TC (n=245, 318)
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
4.5 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Creatine (n=263, 343)
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Glucose (n=242, 312)
|
2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
HDL-C (n=245, 318)
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
LDL-C (n=245, 318)
|
-4.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in BUN, TC, Creatine, Glucose, HDL-C, LDL-C, Bilirubin-Total, Triglycerides, and Uric Acid at the End of Phase 2
Uric Acid (n=266, 347)
|
-0.10 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.10 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
Eosinophils, relative (n=266, 347)
|
2.50 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.20 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline Eosinophils (Relative) and Neutrophils (Relative)
Neutrophils, relative (n=266, 346)
|
67.60 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
58.10 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample; n=number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
Eosinophils, relative (n=266, 347)
|
-0.40 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.20 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Change From Baseline in Eosinophils (Relative) and Neutrophils (Relative)
Neutrophils, relative (n=266, 346)
|
0.25 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.60 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Hemoglobin
|
13.75 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
13.80 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Hemoglobin
|
0.05 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.10 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=265 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=344 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Hematocrit
|
41.30 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
41.10 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=265 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=344 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Hematocrit
|
0.30 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.20 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Outcome measures
| Measure |
Placebo
n=58 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=44 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Homeostasis Model Assessment 2 (HOMA2)-Percent Beta
|
99.95 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
118.70 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Outcome measures
| Measure |
Placebo
n=58 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=44 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Homeostasis Model Assessment 2 HOMA2-Insulin Resistance (IR)
|
1.14 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.42 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Outcome measures
| Measure |
Placebo
n=58 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=44 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Homeostasis Model Assessment 2(HOMA2)-Percent Beta at Phase 2 Endpoint
|
7.70 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
17.05 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint (endpoint of a 13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Outcome measures
| Measure |
Placebo
n=58 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=44 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in HOMA2 Model Assesses Insulin Resistance (HOMA2-IR) at Phase 2 Endpoint
|
0.09 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.15 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=262 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=345 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Platelet Count
|
297.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
226.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=262 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=345 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Platelet Count at Phase 2 Endpoint
|
-4.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=6 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=8 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Prolactin
|
10.0 ng/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
9.5 ng/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=6 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=8 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Prolactin at Phase 2 Endpoint
|
-2.5 ng/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-3.0 ng/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline Leukocytes
|
8.350 x10^3 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.800 x10^3 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
Outcome measures
| Measure |
Placebo
n=266 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=347 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Change From Baseline in Leukocytes at Phase 2 Endpoint
|
-0.100 x10^3 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.200 x10^3 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Outcome measures
| Measure |
Placebo
n=220 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline Abnormal Involuntary Movement Scale (AIMS)
|
0.10 units on a scale
Standard Error 0.042
|
0.08 units on a scale
Standard Error 0.028
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Outcome measures
| Measure |
Placebo
n=220 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) at Phase 2 Endpoint
|
0.05 units on a scale
Standard Error 0.056
|
0.04 units on a scale
Standard Error 0.043
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50.(lower score=less severe). Negative change scores indicate improvement.
Outcome measures
| Measure |
Placebo
n=221 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline in Simpson-Angus Scale (SAS) Total Score
|
10.28 units on a scale
Standard Error 0.054
|
10.30 units on a scale
Standard Error 0.048
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower score=less severe). Negative change scores indicate improvement.
Outcome measures
| Measure |
Placebo
n=221 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score at Phase 2 Endpoint
|
0.44 units on a scale
Standard Error 0.118
|
0.15 units on a scale
Standard Error 0.073
|
SECONDARY outcome
Timeframe: BaselinePopulation: Phase 2 Safety Sample, number of participants with evaluation at time point
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Outcome measures
| Measure |
Placebo
n=221 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline in Barnes Akathisia Global Clinical Assessment
|
0.09 units on a scale
Standard Error 0.022
|
0.14 units on a scale
Standard Error 0.024
|
SECONDARY outcome
Timeframe: Baseline (end of Ph 1), Phase 2 Endpoint. Phase 2 (13- to 24-week Stability and Maintenance of Stability Phase, which followed a 2- to 8-week Screening, Washout, and Confirmation of Partial Nonresponse Phase)Population: Phase 2 Safety Sample, number of participants with evaluation at time point
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Outcome measures
| Measure |
Placebo
n=221 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=295 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Unadjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment at Phase 2 Endpoint
|
0.14 units on a scale
Standard Error 0.043
|
0.07 units on a scale
Standard Error 0.039
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Deaths
|
1 Participants
|
1 Participants
|
|
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Treatment-Emergent SAEs
|
8 Participants
|
11 Participants
|
|
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Treatment-Emergent AEs
|
105 Participants
|
105 Participants
|
|
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Treatment-Emergent AEs in >=2% of Participants
|
49 Participants
|
62 Participants
|
|
Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) in >=2% of Participants, and AEs Leading to Discontinuation During Phase 3
Treatment-Emergent AEs Leading to Discontinuation
|
15 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample; (n=number of participants in sample for each category)
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants with Mild/Grade 1 AE
|
75 Participants
|
75 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants <= 50 Years (n=132, 131)
|
81 Participants
|
84 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants >50 Years (n=34, 36)
|
24 Participants
|
21 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Male Participants (n=70, 81)
|
45 Participants
|
47 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Female Participants (n=96, 86)
|
60 Participants
|
58 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
White Participants (n=63, 74)
|
63 Participants
|
74 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Non-White Participants (n=42, 31)
|
42 Participants
|
31 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants with Moderate/Grade 2 AE
|
53 Participants
|
55 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants with Severe/Grade 3 AE
|
11 Participants
|
9 Participants
|
|
Treatment-Emergent AEs in >=5% of Participants During Phase 3, by Age, Gender, Race, and Maximum Intensity
Participants with Very Severe/Grade 4 AE
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample; n= number of participants with measurement
Heart Rate: increase, ≥120 beats per minute (bpm) and ≥15 relative to baseline (RBL); decrease, ≤50 bpm and ≥15 RBL. Systolic BP: increase, ≥180 mmHg and ≥20 RBL; decrease, ≤90 mmHg and ≥20 RBL. Diastolic BP: increase, ≥105 mmHg and ≥15 RBL; decrease, ≤50 mmHg and ≥15 RBL. For patients missing a baseline value, an on-treatment value was considered potentially clinically relevant if the value meets the criterion value.
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Standing Increase (n=145, 147)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Sitting Increase (n=41, 47)
|
1 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Standing Decrease (n=145, 147)
|
2 Participants
|
1 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Supine Increase (n=165, 164)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Supine Decrease (n=165, 164)
|
2 Participants
|
2 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Sitting Increase (n=41, 47)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
SBP- Sitting Decrease (n=41, 47)
|
0 Participants
|
1 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Standing Increase (n=145, 147)
|
5 Participants
|
1 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Standing Decrease (n=145, 147)
|
0 Participants
|
2 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Supine Increase (n=165, 164)
|
4 Participants
|
3 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Supine Decrease (n=165, 164)
|
1 Participants
|
2 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
DBP- Sitting Decrease (n=41, 47)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Standing Increase (n=145, 147)
|
1 Participants
|
1 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Standing Decrease (n=145, 147)
|
2 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Supine Increase (n=165, 164)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Supine Decrease (n=165, 164)
|
1 Participants
|
1 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Sitting Increase (n=41, 47)
|
0 Participants
|
0 Participants
|
|
Participants With Potentially Clinically Relevant Vital Sign Abnormalities During Phase 3
HR- Sitting Decrease (n=41, 47)
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
Outcome measures
| Measure |
Placebo
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
Lowest Change Value During Phase 3
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-8.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
Baseline
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Systolic BP During Phase 3
Highest Change Value During Phase 3
|
8.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
Outcome measures
| Measure |
Placebo
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
Baseline
|
78.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
79.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
Highest Change Value During Phase 3
|
5.5 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Diastolic BP During Phase 3
Lowest Change Value During Phase 3
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Phase 3 Safety Sample, Week 52 Last Observation Carried Forward (LOCF)
Outcome measures
| Measure |
Placebo
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
Baseline
|
74.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
74.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
Highest Change Value During Phase 3
|
7.5 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
8.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Supine Heart Rate During Phase 3
Lowest Change Value During Phase 3
|
-5.5 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-5.0 beats per minute (bpm)
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
Baseline
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
2.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
Highest Change Value During Phase 3
|
8.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
4.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Systolic BP During Phase 3
Lowest Change Value During Phase 3
|
-3.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
Baseline
|
80.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
80.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
Highest Change Value During Phase 3
|
4.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Diastolic BP During Phase 3
Lowest Change Value During Phase 3
|
-4.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-4.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=33 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
Baseline
|
78.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
76.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
Change from Baseline at Week 52 (LOCF)
|
-4.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
Highest Change Value During Phase 3
|
3.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
4.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Sitting Heart Rate During Phase 3
Lowest Change Value During Phase 3
|
-4.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 beats per minute ?
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
Baseline
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
120.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
Highest Change Value During Phase 3
|
8.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Systolic BP During Phase 3
Lowest Change Value During Phase 3
|
-7.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-8.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
Baseline
|
78.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
78.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
Highest Change Value During Phase 3
|
6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Diastolic BP During Phase 3
Lowest Change Value During Phase 3
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.0 mm Hg
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, During Phase 3 (for highest/lowest values), Week 52Population: Participants in Phase 3 Safety Sample with measurement; Week 52 LOCF
Outcome measures
| Measure |
Placebo
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=143 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
Baseline
|
78.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
78.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
Change from Baseline at Week 52 (LOCF)
|
0.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
Highest Change Value During Phase 3
|
6.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
7.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Values in Standing Heart Rate During Phase 3
Lowest Change Value During Phase 3
|
-7.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.0 beats per minute
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36, 52, During Phase 3 (for highest value)Population: Observed Cases Data Set, Week 52 LOCF; n= number of participants with value at time point
Outcome measures
| Measure |
Placebo
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=160 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Change at Week 52 (n=85, 95)
|
1.66 kg
Standard Error 0.78
|
1.61 kg
Standard Error 0.72
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Baseline (n=161, 160)
|
81.33 kg
Standard Error 1.80
|
80.22 kg
Standard Error 1.79
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Change at Week 12 (n=129, 121)
|
-1.00 kg
Standard Error 0.67
|
0.28 kg
Standard Error 0.69
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Change at Week 24 (n=111, 118)
|
0.35 kg
Standard Error 0.53
|
0.13 kg
Standard Error 0.51
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Change at Week 36 (n=89, 98)
|
0.64 kg
Standard Error 0.65
|
0.59 kg
Standard Error 0.60
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Change at Week 52 (LOCF) (n=161, 160)
|
0.60 kg
Standard Error 0.49
|
1.07 kg
Standard Error 0.49
|
|
Baseline and Adjusted Mean Change From Baseline in Weight
Highest Change Value (n=161, 160)
|
2.39 kg
Standard Error 0.42
|
2.35 kg
Standard Error 0.42
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)Population: Phase 3 Safety Sample; n=number of participants with measurement at time point
Relevant weight gain: \>=7% increase from baseline
Outcome measures
| Measure |
Placebo
n=163 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Week 12 (n=129, 121)
|
3 Participants
|
6 Participants
|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Week 24 (n=111, 118)
|
6 Participants
|
11 Participants
|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Week 36 (n=89, 98)
|
16 Participants
|
12 Participants
|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Week 52 (n=85, 95)
|
16 Participants
|
18 Participants
|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Week 52 (LOCF) (n=161, 160)
|
19 Participants
|
22 Participants
|
|
Number of Participants Showing Relevant Weight Gain During Phase 3
Weight Gain at Any Time (n=163, 164)
|
23 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 36, 52, 52 (LOCF), and throughout Phase 3 (for 'at any time' assessment)Population: Phase 3 Safety Sample; n=number of participants with measurement at time point
Relevant weight loss: \>=7% decrease from baseline
Outcome measures
| Measure |
Placebo
n=163 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Week 12 (n=129, 121)
|
5 Participants
|
6 Participants
|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Week 24 (n=111, 118)
|
7 Participants
|
8 Participants
|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Week 36 (n=89, 98)
|
7 Participants
|
8 Participants
|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Week 52 (n=85, 95)
|
7 Participants
|
5 Participants
|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Week 52 (LOCF) (n=161, 160)
|
13 Participants
|
10 Participants
|
|
Number of Participants Showing Relevant Weight Loss During Phase 3
Weight Gain at Any Time (n=163, 164)
|
18 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36, Week 52, Week 52 (LOCF), During Phase 3 (for lowest/highest values)Population: Phase 3 Safety Sample; n=number of participants with measurement at time point
Outcome measures
| Measure |
Placebo
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=160 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Baseline (n=161, 160)
|
27.0 kg/m^2
Interval 23.7 to 32.3
|
27.9 kg/m^2
Interval 24.1 to 31.5
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Change at Week 12 (n=129, 121)
|
0.0 kg/m^2
Interval -0.6 to 0.4
|
0.2 kg/m^2
Interval -0.1 to 0.8
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Change at Week 24 (n=111, 118)
|
0.1 kg/m^2
Interval -0.4 to 0.6
|
0.2 kg/m^2
Interval -0.4 to 0.9
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Change at Week 36 (n=89, 98)
|
0.1 kg/m^2
Interval -0.5 to 0.9
|
0.4 kg/m^2
Interval -0.4 to 1.2
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Change at Week 52 (n=85, 95)
|
0.5 kg/m^2
Interval -0.1 to 1.4
|
0.7 kg/m^2
Interval -0.2 to 1.6
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Change at Week 52 (LOCF) (n=161, 160)
|
0.2 kg/m^2
Interval -0.6 to 0.9
|
0.5 kg/m^2
Interval -0.3 to 1.2
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Highest Value During Phase 3 (n=161, 160)
|
0.4 kg/m^2
Interval 0.0 to 1.2
|
0.7 kg/m^2
Interval 0.0 to 1.6
|
|
Median Baseline and Change From Baseline in Body Mass Index (BMI) During Phase 3
Lowest Value During Phase 3 (n=161, 160)
|
-0.4 kg/m^2
Interval -1.0 to 0.1
|
-0.1 kg/m^2
Interval -0.9 to 0.3
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample; n=number of participants with measurement
ULN=upper limit of normal; Hb=hemoglobin
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Alkaline Phosphatase ≥ 3 x ULN (n=166,165)
|
2 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Alanine Aminotransferase ≥ 3 x ULN (n=166,165)
|
3 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Aspartate Aminotransferase ≥ 3 x ULN (n=166,165)
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Blood Urea Nitrogen ≥ 30 mg/dL (n=139, 138)
|
3 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Creatine Kinase (n=166,165)
|
8 participants
|
6 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Creatinine ≥ 2.0 mg/dL (n=166,164)
|
0 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Lactate Dehydrogenase (n=166,164)
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Prolactin > ULN (n=163, 158)
|
14 participants
|
14 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Bilirubin Total ≥ 2.0 mg/dL (n=166, 165)
|
2 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Uric Acid≥10.5 mg/dL(M)/≥ 8.5 mg/dL(F)(n=166, 165)
|
4 participants
|
7 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Total Calcium ≤8.2 mg/dL or ≥12 mg/dL (n=166, 165)
|
4 participants
|
7 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Chloride Serum ≤90 mEq/L or ≥118 mEq/L(n=166, 165)
|
1 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Potassium Serum ≤2.5 or ≥6.5 mEq/L (n=166, 164)
|
0 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Sodium Serum ≤126 or ≥156 mEq/L (n=166, 165)
|
1 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Hematocrit ≤37(M) or ≤32(F)3 poi (n=166, 164)
|
7 participants
|
8 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Hb ≤11.5 g/dl (M) / ≤9.5 g/dL (F) (n=166, 164)
|
2 participants
|
4 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Leukocytes (n=166, 164)
|
5 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Eosinophils Relative (Calculated) ≥10 (n=166, 164)
|
6 participants
|
11 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Neutrophils Relative (Calculated) ≤15 (n=166, 164)
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Platelet Count (n=165, 162)
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Urine Glucose (n=166, 165)
|
8 participants
|
8 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Urine Protein (n=166, 165)
|
5 participants
|
4 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Glucose (non-fasting) (n=38, 28)
|
1 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Glucose (fasting) (n=159, 158)
|
26 participants
|
27 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
HDL Cholesterol (combined) (n=166, 165)
|
81 participants
|
91 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
HDL Cholesterol (fasting) (n=160, 159)
|
76 participants
|
88 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
HDL Cholesterol (non-fasting) (n=38, 27)
|
20 participants
|
11 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Total Cholesterol (combined) (n=166, 165)
|
28 participants
|
38 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Total Cholesterol (fasting) (n=160, 159)
|
27 participants
|
35 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Total Cholesterol (non-fasting) (n=38, 27)
|
3 participants
|
7 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
LDL Cholesterol (combined) (n=166, 165)
|
24 participants
|
23 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
LDL Cholesterol (fasting) (n=160, 159)
|
24 participants
|
22 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
LDL Cholesterol (non-fasting) (n=38, 27)
|
1 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Triglycerides (combined) (n=166, 165)
|
59 participants
|
67 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Triglycerides (non-fasting) (n=38, 28)
|
16 participants
|
15 participants
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities During Phase 3
Triglycerides (fasting) (n=160,159)
|
48 participants
|
63 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
Change at Week 52 LOCF
|
1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
8.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
7.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Alkaline Phosphatase (ALP), Phase 3 Safety Sample
Baseline
|
60.5 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
62.5 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
Baseline
|
19.5 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
20.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
Change at Week 52 LOCF
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in ALT, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
6.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
5.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
Baseline
|
20.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
22.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
Change at Week 52 LOCF
|
1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in AST, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
5.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=138 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=135 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
Baseline
|
11.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
12.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
Change at Week 52 LOCF
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in BUN, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
3.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=158 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=156 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
Baseline
|
180.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
181.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
Change at Week 52 LOCF
|
5.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Cholesterol (Fasting), Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
18.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
20.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
Baseline
|
82.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
91.5 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
Change at Week 52 LOCF
|
5.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatine Kinase, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
33.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
28.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
Baseline
|
0.900 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.900 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
Change at Week 52 LOCF
|
0.000 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.000 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Creatinine, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
0.100 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.100 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
The change values reported are the median of (post baseline percentage (of white blood cell count) minus baseline percentage (of white blood cell count).
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
Baseline
|
2.30 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.20 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
Change at Week 52 LOCF
|
0.00 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.10 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Eosinophils (Relative), Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
0.80 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.90 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=157 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=155 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
Baseline
|
90.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
90.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
Change at Week 52 LOCF
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Glucose (Fasting), Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
6.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
7.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
Baseline
|
13.80 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
14.00 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
Change at Week 52 LOCF
|
-0.10 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.10 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hemoglobin, Phase 3 Safety Sample
Lowest Value of Change in Phase 3
|
-0.50 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.60 g/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
Baseline
|
41.40 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
42.15 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
Change at Week 52 LOCF
|
-0.40 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.30 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in Hematocrit, Phase 3 Safety Sample
Lowest Value of Change in Phase 3
|
-1.60 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.90 percentage of total blood volume
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for lowest valuePopulation: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=158 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=156 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
Lowest Value of Change in Phase 3
|
-5.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-5.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
Baseline
|
46.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
45.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Lowest Value of Change in HDL Cholesterol (Fasting), Phase 3 Safety Sample
Change at Week 52 LOCF
|
-1.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest valuePopulation: Phase 3 Safety Sample, participants with measurement
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses beta-cell function (HOMA2-%β) relative to expected normal function (indexed to 100% for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-%Beta is a percentage of 'normal function.'
Outcome measures
| Measure |
Placebo
n=36 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=35 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
Baseline
|
120.0 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
106.90 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
Change at Week 52 LOCF
|
-6.35 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
8.50 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-Percent Beta, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
-10.85 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
5.30 percentage of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest valuePopulation: Phase 3 Safety Sample, participants with measurement
HOMA stands for homeostasis model assessment of insulin resistance and beta-cell function. These are model-based calculations that use fasting insulin and glucose concentrations in order to assess pancreatic beta-cell function and insulin resistance. The HOMA2 model assesses insulin resistance (HOMA2-IR) relative to expected normal function (indexed to 1.0 for normal function) and is based on predictions from experimental human data on the relationship between insulin and glucose in a fasted state. HOMA2-IR is a proportion of 'normal function.'
Outcome measures
| Measure |
Placebo
n=36 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=35 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
Baseline
|
1.24 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.06 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
-0.13 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.13 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in HOMA2-IR, Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
0.20 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.37 proportion of 'normal function'
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
25.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
19.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
Baseline
|
161.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
171.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Lactate Dehydrogenase, Phase 3 Safety Sample
Change at Week 52 LOCF
|
4.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 U/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=158 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=156 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
Baseline
|
104.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
100.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
Change from Baseline in Week 52 LOCF
|
3.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Change Value in LDL Cholesterol (Fasting), Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
16.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
16.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
Baseline
|
61.55 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
62.60 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
Change from Week 52 LOCF
|
-1.30 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.55 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Neutrophils (Relative), Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
-6.45 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-6.20 percent of total white blood cell count
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=163 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=160 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
Baseline
|
252.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
254.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
-1.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-3.5 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
26.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
17.5 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Platelet Count, Phase 3 Safety Sample
Lowest Value of Change During Phase 3
|
-27.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-22.0 x10^9 c/L
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=154 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=147 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
Baseline
|
7.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
6.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
Change from Baseline in Week 52 LOCF
|
2.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Prolactin, Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
3.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.0 ng/mL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=161 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
0.00 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.00 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
Baseline
|
0.40 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.40 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Total Bilirubin, Phase 3 Safety Sample
Highest Value of Change in Phase 3
|
0.10 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.10 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=158 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=156 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
Baseline
|
130.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
134.5 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
4.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Triglycerides (Fasting), Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
37.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
42.0 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
Baseline
|
5.50 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
5.75 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
-0.10 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.00 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Uric Acid, Phase 3 Safety Sample
Highest Value of Change in Uric Acid
|
0.65 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.50 mg/dL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest/lowest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
Highest Value of Change During Phase 3
|
1.100 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
1.100 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
Baseline
|
6.900 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
7.650 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
0.150 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-0.100 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest and Lowest Value of Change in Leukocytes, Phase 3 Safety Sample
Lowest Value of Change During Phase 3
|
-0.900 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-1.000 x 10^3 c/uL
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample
Sinus Tachycardia: ≥120bpm+↑≥15bpm+no current diagnosis of supraventricular (SV) or ventricular tachycardia or atrial fibrillation (AF) or flutter or other rhythm abnormality (RA). Sinus Bradycardia:≥50bpm+↓≥15bpm+no current diagnosis of AF or flutter or other RA. AF:not present→present or present at rate \<100bpm pretreatment to present with rate ≥100bpm+increase of ≥15bpm. AV=atrioventricular; PR=PR interval. Other Intraventricular Block: QRS wave ≥0.12 sec+↑≥0.02 sec+no current diagnosis of left or right bundle branch block. Old Infarction not present→present at ≥12 weeks post study entry.
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Ventricular Premature Beat - not present → present
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Subacute (Recent) Infarction not present → present
|
1 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Old Infarction (see description)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Myocardial Ischemia not present → present
|
1 Participants
|
2 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Symmetrical T-Wave Inversion not present → present
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTc Bazett (QTcB) > 450 msec
|
12 Participants
|
15 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTc Frederica (QTcF) > 450 msec
|
5 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcB > 500 msec
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcF > 500 msec
|
0 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcB Change from Baseline > 30 msec
|
20 Participants
|
25 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcF Change from Baseline > 30 msec
|
10 Participants
|
20 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcB Change from Baseline > 60 msec
|
3 Participants
|
4 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
QTcF Change from Baseline > 60 msec
|
2 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Tachycardia ≥ 120 bpm and ↑ ≥ 15 bpm
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Bradycardia ≤ 50 bpm and ↓ 15 bpm
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Sinus Tachycardia (see description)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Sinus Bradycardia (see description)
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
SV Premature Beat - not present → present
|
1 Participants
|
1 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
SV Tachycardia not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Ventricular Tachycardia not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Atrial Fibrillation (see description)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Atrial Flutter not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
1st Degree AV Block PR ≥0.20 sec and ↑ ≥0.05 sec
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
2nd Degree AV Block not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
3rd Degree AV Block not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Left Bundle Branch Block not present → present
|
12 Participants
|
9 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Right Bundle Branch Block not present → present
|
6 Participants
|
3 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Pre-excitation Syndrome not present → present
|
0 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Other Intraventricular Block (see description)
|
1 Participants
|
0 Participants
|
|
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities During Phase 3
Acute Infarction not present → present
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
Baseline
|
415.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
410.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
3.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
3.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QT Interval Corrected for Heart Rate (QTc) Bazett, Phase 3 Safety Sample
Highest Value of Change in QTc Bazett
|
6.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
12.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
Baseline
|
404.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
400.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
1.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QTc (0.33), Phase 3 Safety Sample
Highest Value of Change in QTc (0.33)
|
3.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
10.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
Baseline
|
155.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
150.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
-2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in PR, Phase 3 Safety Sample
Highest Value of Change in PR
|
2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
4.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
Baseline
|
857.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
870.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
3.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-4.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
Highest Value of Change in RR
|
38.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
20.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in RR, Phase 3 Safety Sample
Lowest Value of Change in RR
|
-15.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-42.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
Baseline
|
89.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
90.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in QRS, Phase 3 Safety Sample
Highest Value of Change in QRS
|
2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
2.0 msecs
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4,8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. It is the most commonly used rating scale for Parkinsonism in clinical trials over the past 25 years. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50(lower scores=less severe). Negative change scores indicate improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 4 (n=160, 161)
|
-0.02 units on a scale
Standard Error 0.07
|
0.04 units on a scale
Standard Error 0.07
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Baseline (n=164, 162)
|
10.48 units on a scale
Standard Error 0.09
|
10.50 units on a scale
Standard Error 0.09
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 8 (n=151, 145)
|
-0.13 units on a scale
Standard Error 0.06
|
-0.03 units on a scale
Standard Error 0.06
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 12 (n=144, 136)
|
-0.20 units on a scale
Standard Error 0.05
|
-0.10 units on a scale
Standard Error 0.05
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 24 (n=113, 120)
|
-0.24 units on a scale
Standard Error 0.07
|
-0.02 units on a scale
Standard Error 0.06
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 36 (n=97, 104)
|
-0.26 units on a scale
Standard Error 0.09
|
0.01 units on a scale
Standard Error 0.08
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 52 (n=85, 95)
|
-0.24 units on a scale
Standard Error 0.08
|
-0.07 units on a scale
Standard Error 0.07
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
-0.20 units on a scale
Standard Error 0.06
|
-0.10 units on a scale
Standard Error 0.06
|
|
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.17 units on a scale
Standard Error 0.10
|
0.53 units on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline, Week 52 (LOCF), Throughout Phase 3 (for highest value)Population: Phase 3 Safety Sample, participants with measurement
Outcome measures
| Measure |
Placebo
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=139 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
Highest Value of Change in Heart Rate
|
1.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
3.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
Baseline
|
70.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
69.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
Change from Baseline at Week 52 LOCF
|
0.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
0.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
|
Median Baseline, Change From Baseline, and Highest Value of Change in Heart Rate, Phase 3 Safety Sample
Lowest Value of Change in Heart Rate
|
-3.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
-2.0 bpm
Values were not prespecified in statistical analysis plan. The purpose of presentation is to flag potential safety signals for further exploration; only medians are presented to help identify direction (and relevance) of any potential safety signal.
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Baseline (n=164, 162)
|
0.11 units on a scale
Standard Error 0.05
|
0.14 units on a scale
Standard Error 0.05
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 4 (n=160, 162)
|
-0.01 units on a scale
Standard Error 0.05
|
0.05 units on a scale
Standard Error 0.04
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 8 (n=151, 145)
|
0.11 units on a scale
Standard Error 0.08
|
0.11 units on a scale
Standard Error 0.08
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 12 (n=144, 136)
|
0.10 units on a scale
Standard Error 0.07
|
-0.01 units on a scale
Standard Error 0.07
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 24 (n=113, 120)
|
0.13 units on a scale
Standard Error 0.09
|
-0.03 units on a scale
Standard Error 0.08
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 36 (n=97, 105)
|
0.08 units on a scale
Standard Error 0.08
|
-0.07 units on a scale
Standard Error 0.08
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 52 (n=85, 96)
|
0.06 units on a scale
Standard Error 0.08
|
-0.02 units on a scale
Standard Error 0.08
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
0.01 units on a scale
Standard Error 0.06
|
0.06 units on a scale
Standard Error 0.06
|
|
Adjusted Mean Change From Baseline in AIMS Total Score During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.16 units on a scale
Standard Error 0.10
|
0.28 units on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 8 Score range from 0 to 4. A negative score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Baseline (n=164, 162)
|
0.04 units on a scale
Standard Error 0.02
|
0.03 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 4 (n=160, 162)
|
-0.01 units on a scale
Standard Error 0.01
|
0.03 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 8 (n=151, 145)
|
0.01 units on a scale
Standard Error 0.02
|
0.02 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 12 (n=144, 136)
|
0.02 units on a scale
Standard Error 0.02
|
0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 24 (n=113, 120)
|
0.02 units on a scale
Standard Error 0.02
|
0.00 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 36 (n=97, 105)
|
0.01 units on a scale
Standard Error 0.02
|
-0.00 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 52 (n=85, 96)
|
-0.00 units on a scale
Standard Error 0.02
|
-0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
0.01 units on a scale
Standard Error 0.02
|
0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 8 During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.03 units on a scale
Standard Error 0.02
|
0.07 units on a scale
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 9 Score range from 0 to 4. A negative score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 12 (n=144, 136)
|
0.03 units on a scale
Standard Error 0.02
|
0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Baseline (n=164, 162)
|
0.01 units on a scale
Standard Error 0.01
|
0.01 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 4 (n=160, 162)
|
-0.01 units on a scale
Standard Error 0.01
|
0.01 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 8 (n=151, 145)
|
0.03 units on a scale
Standard Error 0.02
|
0.02 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 24 (n=113, 120)
|
0.03 units on a scale
Standard Error 0.02
|
0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 36 (n=97, 105)
|
0.03 units on a scale
Standard Error 0.02
|
-0.00 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 52 (n=85, 96)
|
0.02 units on a scale
Standard Error 0.02
|
-0.00 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
0.01 units on a scale
Standard Error 0.01
|
0.01 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 9 During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.04 units on a scale
Standard Error 0.02
|
0.05 units on a scale
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). AIMS Item 10 Score range from 0 to 4. A negative score signifies improvement.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 36 (n=97, 105)
|
0.02 units on a scale
Standard Error 0.02
|
-0.02 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 12 (n=144, 136)
|
0.02 units on a scale
Standard Error 0.02
|
0.00 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Baseline (n=164, 162)
|
0.02 units on a scale
Standard Error 0.01
|
0.04 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 4 (n=160, 162)
|
-0.00 units on a scale
Standard Error 0.01
|
0.03 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 8 (n=151, 145)
|
0.02 units on a scale
Standard Error 0.02
|
0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 24 (n=113, 120)
|
0.05 units on a scale
Standard Error 0.03
|
-0.01 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 52 (n=85, 96)
|
0.01 units on a scale
Standard Error 0.02
|
-0.03 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
0.00 units on a scale
Standard Error 0.01
|
-0.01 units on a scale
Standard Error 0.01
|
|
Adjusted Mean Change From Baseline in AIMS Item 10 During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.04 units on a scale
Standard Error 0.02
|
0.06 units on a scale
Standard Error 0.02
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, 24, 36, 52, throughout Phase 3 (for Highest Value of Change)Population: Phase 3 Safety Sample, OC Data Set and Week 52 LOCF; n=number of participants with evaluation at time point
The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Outcome measures
| Measure |
Placebo
n=164 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=162 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 8 (n=151, 144)
|
-0.06 units on a scale
Standard Error 0.02
|
-0.04 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Baseline (n=164, 162)
|
0.10 units on a scale
Standard Error 0.04
|
0.16 units on a scale
Standard Error 0.04
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 4 (n=160, 162)
|
-0.01 units on a scale
Standard Error 0.03
|
0.01 units on a scale
Standard Error 0.03
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 12 (n=144, 136)
|
-0.07 units on a scale
Standard Error 0.03
|
-0.03 units on a scale
Standard Error 0.03
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 24 (n=113, 120)
|
-0.06 units on a scale
Standard Error 0.03
|
-0.04 units on a scale
Standard Error 0.03
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 36 (n=97, 104)
|
-0.09 units on a scale
Standard Error 0.03
|
-0.05 units on a scale
Standard Error 0.03
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 52 (n=85, 96)
|
-0.10 units on a scale
Standard Error 0.03
|
-0.07 units on a scale
Standard Error 0.03
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Change at Week 52 LOCF (n=164, 162)
|
-0.06 units on a scale
Standard Error 0.02
|
-0.05 units on a scale
Standard Error 0.02
|
|
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment During Phase 3
Highest Value in Change During Phase 3 (n=164,162)
|
0.07 units on a scale
Standard Error 0.04
|
0.11 units on a scale
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Phase 3 (A 52-Week Assessment of Relapse Phase following Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Phase 3 Safety Sample
Outcome measures
| Measure |
Placebo
n=166 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=167 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Any EPS Medications
|
36 participants
|
40 participants
|
|
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Cardiovascular System-Propanolol
|
18 participants
|
21 participants
|
|
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Nervous System-Benztropine
|
10 participants
|
19 participants
|
|
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Nervous System-Biperiden
|
4 participants
|
2 participants
|
|
Number of Participants Taking Concomitant Medications for Potential Treatment of Extrapyramidal Syndrome (EPS) During Phase 3
Nervous System-Trihexyphenidyl
|
11 participants
|
10 participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72 of LTE Phase. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Baseline (N=19, 23)
|
1.26 units on a scale
Standard Error 0.104
|
1.35 units on a scale
Standard Error 0.102
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 64 (n=5, 4)
|
0.00 units on a scale
Standard Error 0.000
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 8 (n=19, 23)
|
-0.26 units on a scale
Standard Error 0.104
|
-0.30 units on a scale
Standard Error 0.098
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 16 (n=18, 23)
|
-0.28 units on a scale
Standard Error 0.109
|
-0.30 units on a scale
Standard Error 0.098
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 24 (n=17, 20)
|
-0.29 units on a scale
Standard Error 0.114
|
-0.40 units on a scale
Standard Error 0.112
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 32 (n=15, 15)
|
0.00 units on a scale
Standard Error 0.309
|
-0.33 units on a scale
Standard Error 0.126
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 40 (n=9, 12)
|
-0.11 units on a scale
Standard Error 0.111
|
-0.33 units on a scale
Standard Error 0.142
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 48 (n=9, 9)
|
-0.11 units on a scale
Standard Error 0.111
|
-0.22 units on a scale
Standard Error 0.147
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 56 (n=5, 9)
|
0.00 units on a scale
Standard Error 0.000
|
-0.22 units on a scale
Standard Error 0.147
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP (Mania)
Mean Change at Week 72 (n=1, 2)
|
0.00 units on a scale
Standard Error 0.000
|
-0.50 units on a scale
Standard Error 0.500
|
SECONDARY outcome
Timeframe: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: extension phase participants, last observation carried forward (LOCF)
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Change From Baseline in CGI-BP (Mania) Severity of Illness at Extension Phase Endpoint
|
-0.05 units on a scale
Standard Error 0.247
|
-0.35 units on a scale
Standard Error 0.102
|
SECONDARY outcome
Timeframe: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: extension phase participants, last observation carried forward (LOCF)
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Depression) at Extension Phase Endpoint
|
-0.16 units on a scale
Standard Error 0.138
|
0.00 units on a scale
Standard Error 0.000
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 32 (n=15, 15)
|
-0.20 units on a scale
Standard Error 0.175
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 24 (n=17, 20)
|
-0.12 units on a scale
Standard Error 0.146
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Baseline (N=19, 23)
|
1.21 units on a scale
Standard Error 0.123
|
1.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 8 (n=19, 23)
|
-0.11 units on a scale
Standard Error 0.130
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 16 (n=18, 23)
|
-0.11 units on a scale
Standard Error 0.137
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 40 (n=9, 12)
|
-0.11 units on a scale
Standard Error 0.200
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 48 (n=9, 9)
|
-0.11 units on a scale
Standard Error 0.200
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 56 (n=5, 9)
|
-0.20 units on a scale
Standard Error 0.200
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 64 (n=5, 4)
|
-0.20 units on a scale
Standard Error 0.200
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Depression) Through Extension Phase
Mean Change at Week 72 (n=1, 2)
|
0.00 units on a scale
Standard Error 0.00
|
0.00 units on a scale
Standard Error 0.000
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Number of participants analyzed=extension phase participants, observed cases (OC) data set; n=number of participants evaluated at time point
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 48 (n=9, 9)
|
-0.22 units on a scale
Standard Error 0.222
|
-0.22 units on a scale
Standard Error 0.147
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 56 (n=5, 9)
|
-0.20 units on a scale
Standard Error 0.200
|
-0.22 units on a scale
Standard Error 0.147
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 64 (n=5, 4)
|
-0.20 units on a scale
Standard Error 0.200
|
0.00 units on a scale
Standard Error 0.000
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 72 (n=1, 2)
|
0.00 units on a scale
Standard Error 0.00
|
-0.50 units on a scale
Standard Error 0.500
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Baseline (N=19, 23)
|
1.37 units on a scale
Standard Error 0.114
|
1.35 units on a scale
Standard Error 0.102
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 8 (n=19, 23)
|
-0.26 units on a scale
Standard Error 0.129
|
-0.30 units on a scale
Standard Error 0.098
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 16 (n=18, 23)
|
-0.28 units on a scale
Standard Error 0.135
|
-0.30 units on a scale
Standard Error 0.098
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 40 (n=9, 12)
|
-0.22 units on a scale
Standard Error 0.222
|
-0.33 units on a scale
Standard Error 0.142
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 24 (n=17, 20)
|
-0.29 units on a scale
Standard Error 0.143
|
-0.40 units on a scale
Standard Error 0.112
|
|
Extension Phase: Mean Baseline and Mean Change From Baseline in CGI-BP Severity of Illness (Overall) Through Extension Phase
Mean Change at Week 32 (n=15, 15)
|
-0.07 units on a scale
Standard Error 0.330
|
-0.33 units on a scale
Standard Error 0.126
|
SECONDARY outcome
Timeframe: Baseline, Extension Phase Endpoint. LTE Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: extension phase participants, last observation carried forward (LOCF)
Clinical Global Impression-Bipolar (CGI-BP) assesses global illness severity and change in patients with bipolar disorder. Patients are rated on Change from Preceding Phase (mania, depression and overall bipolar illness) items (also a 7-point scale \[1 to 7\], with 1 being normal and 7 being very severely ill). A negative change score signifies improvement.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Mean Change From Baseline in CGI-BP Severity of Illness (Overall) at Extension Phase Endpoint
|
-0.11 units on a scale
Standard Error 0.264
|
-0.35 units on a scale
Standard Error 0.102
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Extension Phase Safety Sample
Participants with Adverse Events (AEs), Deaths, Serious AEs (SAEs), and AEs leading to study discontinuation. AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
Deaths
|
0 Participants
|
0 Participants
|
|
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
SAEs
|
0 Participants
|
0 Participants
|
|
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
AEs
|
5 Participants
|
8 Participants
|
|
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
Discontinuations due to AEs
|
1 Participants
|
0 Participants
|
|
Extension Phase: Deaths, Adverse Events (AES), Serious Adverse Events (SAEs), and Discontinuations
Treatment-related AEs
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Number of Participants Analyzed=Participants in Extension Phase Safety Sample; n=number of participants with evaluation
Metabolic abnormalities considered by the investigator as clinically relevant. (Need normal values for each.)
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Glucose, non-fasting (n=3,1)
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Glucose, fasting (n=17, 22)
|
2 Participants
|
3 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
HDL Cholesterol, combined (n=18, 22)
|
12 Participants
|
11 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
HDL Cholesterol, fasting (n=17, 22)
|
12 Participants
|
11 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
HDL Cholesterol, non-fasting (n=2, 1)
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Total Cholesterol, combined (n=18, 22)
|
0 Participants
|
1 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Total Cholesterol, fasting (n=17, 22)
|
0 Participants
|
1 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Total Cholesterol, non-fasting (n=2, 1)
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
LDL Cholesterol, combined (n=18, 22)
|
1 Participants
|
3 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
LDL Cholesterol, fasting (n=17, 22)
|
1 Participants
|
3 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
LDL Cholesterol, non-fasting (n=2, 1)
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Triglycerides, combined (n=18, 22)
|
4 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Triglycerides, fasting (n=17, 22)
|
4 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Metabolic Laboratory Abnormalities During Extension Phase
Triglycerides, non-fasting (n=2, 1)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Extension Phase Safety Sample
Vital sign abnormalities considered by the investigator as clinically relevant.
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Systolic Blood Pressure Increase
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Systolic Blood Pressure Decrease
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Diastolic Blood Pressure Increase
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Diastolic Blood Pressure Decrease
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Heart Rate Increase
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Heart Rate Decrease
|
0 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Weight Increase
|
1 Participants
|
7 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Vital Sign Abnormalities
Weight Decrease
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Participants in Extension Phase Safety Sample with AEs
AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. By Common Terminology Criteria Version 3.0 (CTC v3) Grade (Gr): Gr 1 (mild); Gr 2 (moderate); Gr 3 (severe); Gr 4 (life-threatening); Gr 5 (death).
Outcome measures
| Measure |
Placebo
n=19 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=23 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Adverse Events (AEs), by Maximum Intensity
Mild / Grade 1
|
4 Participants
|
7 Participants
|
|
Extension Phase: Adverse Events (AEs), by Maximum Intensity
Moderate / Grade 2
|
1 Participants
|
2 Participants
|
|
Extension Phase: Adverse Events (AEs), by Maximum Intensity
Severe / Grade 3
|
0 Participants
|
0 Participants
|
|
Extension Phase: Adverse Events (AEs), by Maximum Intensity
Very Severe / Grade 4
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Participants in Extension Phase Safety Sample with laboratory evaluation
Chemistry, hematology, and urinalysis abnormalities considered by the investigator as clinically relevant. Hematocrit: ≤37%(M)/≤32%(F)+3 percentage pts↓from baseline.
Outcome measures
| Measure |
Placebo
n=18 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=22 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Creatine Kinase >= 3 x ULN
|
1 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Hematocrit (see description)
|
2 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Hemoglobin ≤11.5 g/dL(M)/≤9.5 g/dL(F)
|
2 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Eosinophils relative (calculated) ≥10%
|
2 Participants
|
2 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant Laboratory Abnormalities
Urine Glucose (any glucose in the urine)
|
0 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: From first day until 30 days after the last dose of double-blind dosing in the Extension Phase (A 72-week Extension Phase [until study unblinding] following Phase 3 [52 weeks], Phase 2 [13 to 24 weeks] and Phase 1 [2 to 8 weeks])Population: Participants in Extension Phase Safety Sample with ECG evaluation
ECG abnormalities considered by the investigator as clinically relevant.Left Bundle Branch Block: Not present at Baseline--\> present post-baseline.
Outcome measures
| Measure |
Placebo
n=17 Participants
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
Aripiprazole
n=21 Participants
Phase 3 (52 Week Assessment of Relapse Phase): aripiprazole 10-mg and 15-mg oral tablets and 250-mg and 300-mg oral lithium tablets or 250-mg Depakote/valproic acid oral tablets
|
|---|---|---|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
Left Bundle Branch Block (see description)
|
4 Participants
|
1 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcB > 450 msec
|
1 Participants
|
3 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcF > 450 msec
|
1 Participants
|
1 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcB Change from Baseline > 30 msec
|
3 Participants
|
5 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcF Change from Baseline > 30 msec
|
4 Participants
|
3 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcB Change from Baseline > 60 msec
|
1 Participants
|
0 Participants
|
|
Extension Phase: Participants With Potentially Clinically Relevant ECG Abnormalities
QTcF Change from Baseline > 60 msec
|
1 Participants
|
0 Participants
|
Adverse Events
Single-Blind Aripiprazole
Serious events: 15 serious events
Other events: 402 other events
Deaths: 0 deaths
Double-Blind Placebo
Serious events: 8 serious events
Other events: 61 other events
Deaths: 0 deaths
Double-Blind Aripiprazole
Serious events: 11 serious events
Other events: 68 other events
Deaths: 0 deaths
Extension Phase Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Extension Phase Aripiprazole
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Single-Blind Aripiprazole
n=682 participants at risk
Phase 1 (2 to 8 Week Screening, Washout and Confirmation of Partial Nonresponse Phase): lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml. Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Double-Blind Placebo
n=166 participants at risk
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Double-Blind Aripiprazole
n=167 participants at risk
Phase 3 (52 Week Assessment of Relapse Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Extension Phase Placebo
n=19 participants at risk
Phase 4 (Extension Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Extension Phase Aripiprazole
n=23 participants at risk
Phase 4 (Extension Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
|---|---|---|---|---|---|
|
Psychiatric disorders
MANIA
|
0.00%
0/682
|
1.2%
2/166
|
1.2%
2/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
AGITATION
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
AGGRESSION
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
DEPRESSION
|
0.44%
3/682
|
1.2%
2/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
ALCOHOL ABUSE
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
SUICIDE ATTEMPT
|
0.15%
1/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
BIPOLAR DISORDER
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
MAJOR DEPRESSION
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
SUICIDAL IDEATION
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
BIPOLAR I DISORDER
|
0.00%
0/682
|
0.60%
1/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
PSYCHOTIC DISORDER
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
HALLUCINATION, VISUAL
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Psychiatric disorders
HALLUCINATION, AUDITORY
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
RADIAL NERVE PALSY
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Infections and infestations
PNEUMONIA
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/682
|
1.2%
2/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Infections and infestations
APPENDICITIS
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Infections and infestations
GASTRITIS VIRAL
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Renal and urinary disorders
RENAL FAILURE ACUTE
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Reproductive system and breast disorders
BARTHOLIN'S CYST
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Injury, poisoning and procedural complications
ACCIDENTAL OVERDOSE
|
0.29%
2/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
General disorders
CHEST PAIN
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
General disorders
DECAPITATION
|
0.00%
0/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER
|
0.00%
0/682
|
0.60%
1/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
0.00%
0/19
|
0.00%
0/23
|
Other adverse events
| Measure |
Single-Blind Aripiprazole
n=682 participants at risk
Phase 1 (2 to 8 Week Screening, Washout and Confirmation of Partial Nonresponse Phase): lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml. Phase 2 (13 to 24 Week Stability and Maintenance of Stability Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Double-Blind Placebo
n=166 participants at risk
Phase 3 (52 Week Assessment of Relapse Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Double-Blind Aripiprazole
n=167 participants at risk
Phase 3 (52 Week Assessment of Relapse Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Extension Phase Placebo
n=19 participants at risk
Phase 4 (Extension Phase): matching placebo oral tablets and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
Extension Phase Aripiprazole
n=23 participants at risk
Phase 4 (Extension Phase): 10-mg, 15-mg, or 30-mg doses of aripiprazole and lithium: 0.6-1.0 mmol/L or valproate 50-125 µg/ml.
|
|---|---|---|---|---|---|
|
Investigations
WEIGHT INCREASED
|
4.1%
28/682
|
6.6%
11/166
|
9.0%
15/167
|
0.00%
0/19
|
4.3%
1/23
|
|
Psychiatric disorders
INSOMNIA
|
8.9%
61/682
|
9.6%
16/166
|
5.4%
9/167
|
0.00%
0/19
|
8.7%
2/23
|
|
Psychiatric disorders
MOOD ALTERED
|
0.15%
1/682
|
0.60%
1/166
|
0.00%
0/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Psychiatric disorders
RESTLESSNESS
|
5.3%
36/682
|
0.00%
0/166
|
1.2%
2/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
TREMOR
|
13.8%
94/682
|
2.4%
4/166
|
6.0%
10/167
|
0.00%
0/19
|
4.3%
1/23
|
|
Nervous system disorders
HEADACHE
|
8.9%
61/682
|
10.8%
18/166
|
13.2%
22/167
|
5.3%
1/19
|
4.3%
1/23
|
|
Nervous system disorders
SEDATION
|
5.9%
40/682
|
0.00%
0/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
AKATHISIA
|
14.5%
99/682
|
1.8%
3/166
|
3.6%
6/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
DIZZINESS
|
6.3%
43/682
|
1.8%
3/166
|
4.2%
7/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
SOMNOLENCE
|
7.8%
53/682
|
1.8%
3/166
|
0.60%
1/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Nervous system disorders
EXTRAPYRAMIDAL DISORDER
|
5.4%
37/682
|
0.60%
1/166
|
3.0%
5/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Gastrointestinal disorders
NAUSEA
|
8.8%
60/682
|
2.4%
4/166
|
3.0%
5/167
|
0.00%
0/19
|
0.00%
0/23
|
|
Gastrointestinal disorders
DIARRHOEA
|
5.7%
39/682
|
3.6%
6/166
|
4.2%
7/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Gastrointestinal disorders
GASTRITIS
|
0.15%
1/682
|
1.8%
3/166
|
0.60%
1/167
|
10.5%
2/19
|
0.00%
0/23
|
|
Gastrointestinal disorders
ANAL FISSURE
|
0.00%
0/682
|
0.00%
0/166
|
0.00%
0/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
0.15%
1/682
|
0.00%
0/166
|
0.00%
0/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Skin and subcutaneous tissue disorders
DERMATITIS
|
0.15%
1/682
|
0.60%
1/166
|
0.00%
0/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.73%
5/682
|
1.8%
3/166
|
1.2%
2/167
|
5.3%
1/19
|
0.00%
0/23
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.59%
4/682
|
0.60%
1/166
|
1.8%
3/167
|
5.3%
1/19
|
0.00%
0/23
|
|
General disorders
PYREXIA
|
1.9%
13/682
|
3.0%
5/166
|
4.2%
7/167
|
5.3%
1/19
|
4.3%
1/23
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER