Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Aripiprazole Administered With Lithium or Valproate Over 12 Weeks in the Treatment of Mania in Bipolar I Disorder (NCT NCT00665366)
NCT ID: NCT00665366
Last Updated: 2013-12-02
Results Overview
The YMRS is a clinician-administered scale, consisting of 11 multiple choice items, and used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-though disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
COMPLETED
PHASE3
493 participants
Baseline to Week 12
2013-12-02
Participant Flow
Of 493 participants enrolled, 370 were randomized, and 369 received treatment with double-blind study medication.
Participant milestones
| Measure |
Placebo + Valproate or Lithium
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
Aripiprazole + Valproate or Lithium
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
|---|---|---|
|
Overall Study
STARTED
|
189
|
181
|
|
Overall Study
COMPLETED
|
131
|
122
|
|
Overall Study
NOT COMPLETED
|
58
|
59
|
Reasons for withdrawal
| Measure |
Placebo + Valproate or Lithium
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
Aripiprazole + Valproate or Lithium
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
|---|---|---|
|
Overall Study
Lack of Efficacy
|
11
|
10
|
|
Overall Study
Adverse Event
|
25
|
23
|
|
Overall Study
Withdrawal by Subject
|
11
|
14
|
|
Overall Study
Lost to Follow-up
|
3
|
5
|
|
Overall Study
Poor compliance/noncompliance
|
3
|
5
|
|
Overall Study
Pregnancy
|
1
|
0
|
|
Overall Study
No longer meets study criteria
|
0
|
1
|
|
Overall Study
Other reasons
|
4
|
1
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Aripiprazole Administered With Lithium or Valproate Over 12 Weeks in the Treatment of Mania in Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
Placebo + Valproate or Lithium
n=189 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
Aripiprazole + Valproate or Lithium
n=181 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Total
n=370 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
44.92 Years
STANDARD_DEVIATION 12.99 • n=5 Participants
|
44.37 Years
STANDARD_DEVIATION 12.13 • n=7 Participants
|
44.65 Years
STANDARD_DEVIATION 12.57 • n=5 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
200 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
90 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
170 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
179 Participants
n=5 Participants
|
172 Participants
n=7 Participants
|
351 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug.
The YMRS is a clinician-administered scale, consisting of 11 multiple choice items, and used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-though disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Total Score on the Young Mania Rating Scale (YMRS) (LOCF Data Set)
|
-13.57 Units on a scale
Standard Error 0.78
|
-11.54 Units on a scale
Standard Error 0.78
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
Week 3 (n=183, 174)
|
-0.93 Units on a scale
Standard Error 0.08
|
-0.97 Units on a scale
Standard Error 0.08
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
Week 6 (n=186, 176)
|
-1.46 Units on a scale
Standard Error 0.10
|
-1.35 Units on a scale
Standard Error 0.09
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
Week 9 (n=186, 176)
|
-1.83 Units on a scale
Standard Error 0.11
|
-1.55 Units on a scale
Standard Error 0.10
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Mania) Scale (LOCF Data Set)
Week 12 (n=186, 176)
|
-2.07 Units on a scale
Standard Error 0.11
|
-1.78 Units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
Adjusted mean change. The CGI-BP is a scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
Week 3 (n=183, 174)
|
-0.09 Units on a scale
Standard Error 0.05
|
-0.01 Units on a scale
Standard Error 0.05
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
Week 6 (n=186, 176)
|
-0.01 Units on a scale
Standard Error 0.06
|
-0.02 Units on a scale
Standard Error 0.06
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
Week 9 (n=186, 176)
|
0.11 Units on a scale
Standard Error 0.07
|
-0.04 Units on a scale
Standard Error 0.07
|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Depression) Scale (LOCF Data Set)
Week 12 (n=186, 176)
|
0.14 Units on a scale
Standard Error 0.08
|
-0.03 Units on a scale
Standard Error 0.08
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
Adjusted mean change. The CGI-BP is scale used to assess a clinician's impression of a patient's illness. Each patient is rated at baseline and at subsequent visits on items related to severity of depression, mania, and overall bipolar illness. The CGI-BP is a 7-point scale, with scores ranging from 1=normal/not ill to 7=very severely ill. Higher total score indicates greater severity of illness. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Score on Clinical Global Impression-Bipolar Version (CGI-BP) Severity of Illness (Overall) Scale at Week 12 (LOCF Data Set)
|
-1.59 Units on a scale
Standard Error 0.11
|
-1.51 Units on a scale
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 outcomes research evaluation after the start of study drug. n=number of evaluable participants.
The FAST is an interview-administered instrument used to assess the main functioning problems that patients with bipolar disorder experience. Participants are rated at Baseline, Week 3, Week 6, Week 9, and Week 12/End of Study Visit. The FAST consists of 24 items that assess impairment or disability in 6 specific areas of functioning, categorized as the subscales: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal (IP) relationships, and leisure time. All items are rated using a 4-point scale, 0=no difficulty, 1=mild difficulty, 2=moderate difficulty, and 3=severe difficulty. The global score is the sum of the scores of all items and ranges from 0 (0\*24)to 96 (4\*24). The higher the global score, the higher the level of impairment. function=functioning. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=181 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=189 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Leisure time score: Week 12 (n=182, 171)
|
-0.59 Units on a scale
Standard Error 0.13
|
-0.68 Units on a scale
Standard Error 0.13
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Financial issues score: Week 3 (n=179, 169)
|
-0.48 Units on a scale
Standard Error 0.12
|
-0.78 Units on a scale
Standard Error 0.12
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Financial issues score: Week 6 (n=182, 171)
|
-0.76 Units on a scale
Standard Error 0.13
|
-1.16 Units on a scale
Standard Error 0.12
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Financial issues score: Week 9 (n=182, 171)
|
-0.99 Units on a scale
Standard Error 0.13
|
-1.25 Units on a scale
Standard Error 0.13
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Financial issues score: Week 12 (n=182, 171)
|
-1.07 Units on a scale
Standard Error 0.13
|
-1.30 Units on a scale
Standard Error 0.12
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Total score: Week 3 (n=179, 169)
|
-5.00 Units on a scale
Standard Error 0.87
|
-5.68 Units on a scale
Standard Error 0.86
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Total score: Week 6 (n=182, 171)
|
-6.93 Units on a scale
Standard Error 0.99
|
-8.59 Units on a scale
Standard Error 0.98
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Total score: Week 9 (n=182, 171)
|
-7.71 Units on a scale
Standard Error 1.07
|
-9.18 Units on a scale
Standard Error 1.06
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Total score: Week 12 (n=182, 171)
|
-8.51 Units on a scale
Standard Error 1.10
|
-10.39 Units on a scale
Standard Error 1.09
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Autonomy score: Week 3 (n=179, 169)
|
-0.93 Units on a scale
Standard Error 0.18
|
-0.93 Units on a scale
Standard Error 0.18
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Autonomy score: Week 6 (n=182, 171)
|
-1.11 Units on a scale
Standard Error 0.19
|
-1.44 Units on a scale
Standard Error 0.19
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Autonomy score: Week 9 (n=182, 171)
|
-1.20 Units on a scale
Standard Error 0.21
|
-1.56 Units on a scale
Standard Error 0.21
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Cognitive function score: Week 12 (n=182, 171)
|
-1.91 Units on a scale
Standard Error 0.28
|
-2.59 Units on a scale
Standard Error 0.27
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Autonomy score: Week 12 (n=182, 171)
|
-1.45 Units on a scale
Standard Error 0.21
|
-1.84 Units on a scale
Standard Error 0.21
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
IP relationships score: Week 3 (n=179,169)
|
-1.33 Units on a scale
Standard Error 0.26
|
-1.57 Units on a scale
Standard Error 0.25
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Occupational function score: Week 3 (n=179, 169)
|
-1.00 Units on a scale
Standard Error 0.25
|
-0.65 Units on a scale
Standard Error 0.25
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Occupational function score: Week 6 (n=182, 171)
|
-1.40 Units on a scale
Standard Error 0.29
|
-1.23 Units on a scale
Standard Error 0.29
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Occupational function score: Week 9 (n=182, 171)
|
-1.22 Units on a scale
Standard Error 0.30
|
-1.20 Units on a scale
Standard Error 0.30
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Occupational function score: Week 12 (n=182, 171)
|
-1.24 Units on a scale
Standard Error 0.30
|
-1.49 Units on a scale
Standard Error 0.30
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Cognitive function score: Week 3 (n=179, 169)
|
-0.99 Units on a scale
Standard Error 0.23
|
-1.33 Units on a scale
Standard Error 0.23
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
IP relationships score: Week 6 (n=182, 171)
|
-1.91 Units on a scale
Standard Error 0.29
|
-2.20 Units on a scale
Standard Error 0.28
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
IP relationships score: Week 9 (n=182, 171)
|
-2.14 Units on a scale
Standard Error 0.31
|
-2.41 Units on a scale
Standard Error 0.31
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
IP relationships score: Week 12 (n=182, 171)
|
-2.31 Units on a scale
Standard Error 0.31
|
-2.57 Units on a scale
Standard Error 0.31
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Leisure time score: Week 3 (n=179, 169)
|
-0.28 Units on a scale
Standard Error 0.11
|
-0.50 Units on a scale
Standard Error 0.11
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Leisure time score: Week 6 (n=182, 171)
|
-0.34 Units on a scale
Standard Error 0.13
|
-0.53 Units on a scale
Standard Error 0.13
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Leisure time score: Week 9 (n=182, 171)
|
-0.52 Units on a scale
Standard Error 0.13
|
-0.52 Units on a scale
Standard Error 0.13
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Cognitive function score: Week 6 (n=182, 171)
|
-1.46 Units on a scale
Standard Error 0.26
|
-2.12 Units on a scale
Standard Error 0.26
|
|
Change From Baseline in Total and Subscale Scores on the Functional Assessment Short Test (FAST)(LOCF Data Set)
Cognitive function score: Week 9 (n=182, 171)
|
-1.68 Units on a scale
Standard Error 0.27
|
-2.30 Units on a scale
Standard Error 0.26
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
Response on the YMRS is defined as a 50% or greater improvement from baseline in YMRS total score. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, content, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. OC=observed cases.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
Week 3 (n=183, 174)
|
29.3 Percentage of participants
|
26.2 Percentage of participants
|
|
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
Week 6 (n=186, 176)
|
49.4 Percentage of participants
|
46.2 Percentage of participants
|
|
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
Week 9 (n=186, 176)
|
64.2 Percentage of participants
|
53.8 Percentage of participants
|
|
Percentage of Participants Showing A Response From Baseline on the Young Mania Rating Scale (YMRS)(OC Data Set)
Week 12 (n=186, 176)
|
68.8 Percentage of participants
|
61.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3,6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 efficacy evaluation after the start of study drug. n=number of evaluable participants.
Remission is defined as a YMRS total score of 12 or less. The YMRS is clinician-administered and consists of 11 multiple choice items. It is used to assess a patient's manic symptoms and clinical condition over the previous 48 hours. Total scores range from 0 to 60, with 12 or greater signifying hypomania or mania. Each item is given a severity rating ranging from 0 to 8 or 0 to 4. Items for the scale are based on the core symptoms of mania: elevated mood, increased motor activity, sexual interest, sleep, irritability, speech (rate and amount), language-thought disorder, disruptive-aggressive behavior, appearance, and insight. Scores for each item reflect the severity of that symptom in the patient. The test is administered during a clinical interview typically lasting 15-30 minutes. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
Week 3 (n=183, 174)
|
31.0 Percentage of participants
|
30.6 Percentage of participants
|
|
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
Week 6 (n=186, 176)
|
51.7 Percentage of participants
|
48.9 Percentage of participants
|
|
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
Week 9 (n=186, 176)
|
65.9 Percentage of participants
|
57.0 Percentage of participants
|
|
Percentage of Participants Showing Remission in the Young Mania Rating Scale (YMRS) Score From Baseline (LOCF Data Set)
Week 12 (n=186, 176)
|
69.9 Percentage of participants
|
64.0 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Weeks 6 and 12Population: All randomized participants who received at least 1 dose of study medication and had at least 1 outcome research evaluation after the start of study drug. n=number of evaluable participants.
Adjusted mean change. The LIFE-RIFT total score ranges from 4 to 20 and is the sum of scores of 4 items: work, interpersonal relations, satisfaction, and recreation. A negative change score signifies improvement. OC=observed cases; LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set)
Week 6 (n=146, 135)
|
-1.45 Units on a scale
Standard Error 0.23
|
-2.13 Units on a scale
Standard Error 0.22
|
|
Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set)
Week 12 (n=123, 115)
|
-2.37 Units on a scale
Standard Error 0.28
|
-3.20 Units on a scale
Standard Error 0.28
|
|
Change From Baseline in Total Score on the Longitudinal Interval Follow-up Evaluation-Rating Impaired Functioning Tool (LIFE-RIFT)(OC Data Set and Week 12 LOCF Data Set)
Week 12 (LOCF) (n=165, 150)
|
-1.69 Units on a scale
Standard Error 0.28
|
-2.30 Units on a scale
Standard Error 0.27
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication and who had at least 1 outcomes research evaluation after the start of study drug. n=number of evaluable participants.
Adjusted Mean Scores. The PGI-I is a self-administered 7-point scale, with scores ranging from 1 (very much improved) to 7 (very much worse), that assesses the improvement or worsening of a patient's illness relative to baseline at the beginning of the intervention. Scores: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. OC=observed cases.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
Week 3 (n=178, 168)
|
2.99 Units on a scale
Standard Error 0.10
|
2.94 Units on a scale
Standard Error 0.10
|
|
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
Week 6 (n=151, 140)
|
2.64 Units on a scale
Standard Error 0.11
|
2.39 Units on a scale
Standard Error 0.11
|
|
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
Week 12 (n=127, 119)
|
2.24 Units on a scale
Standard Error 0.12
|
2.02 Units on a scale
Standard Error 0.12
|
|
Participant Scores on Patient Global Impression Improvement (PGI-I) Scale (OC Data Set)
Week 12 (LOCF) (n=181, 173)
|
2.88 Units on a scale
Standard Error 0.13
|
2.60 Units on a scale
Standard Error 0.13
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and 12Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
Adjusted mean change.OC=observed cases; LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Week 3 (n=177, 171)
|
0.14 Kilograms
Standard Error 0.15
|
-0.06 Kilograms
Standard Error 0.16
|
|
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Week 6 (n=152,144)
|
0.29 Kilograms
Standard Error 0.21
|
-0.02 Kilograms
Standard Error 0.20
|
|
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Week 9 (n=142, 128)
|
-0.01 Kilograms
Standard Error 0.26
|
0.07 Kilograms
Standard Error 0.26
|
|
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Week 12 (n=133, 123)
|
0.02 Kilograms
Standard Error 0.29
|
0.22 Kilograms
Standard Error 0.29
|
|
Change From Baseline in Participant Weight (OC Data Set and Week 12 LOCF Data Set)
Week 12 (LOCF) (n=183, 174)
|
0.11 Kilograms
Standard Error 0.23
|
0.11 Kilograms
Standard Error 0.24
|
SECONDARY outcome
Timeframe: Baseline to Weeks 3, 6, 9, and12Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
Relevant weight gain=7% or greater increase in weight; relevant weight loss=7% or greater decrease in weight. LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)
Weight gain: Week 12 (n=184,174)
|
5.2 Percentage of participants
|
4.3 Percentage of participants
|
|
Percentage of Participants With Relevant Weight Gain or Weight Loss From Baseline at Week 12 (LOCF Data Set)
Weight loss: Week 12 (n=184,174)
|
4.0 Percentage of participants
|
2.7 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: All randomized participants who received at least 1 dose of study medication. n=number of evaluable participants.
BMI=Weight in kilograms /(Height in meters\^2). LOCF=last observation carried forward.
Outcome measures
| Measure |
Aripiprazole + Valproate or Lithium
n=176 Participants
Participants randomly received aripiprazole as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks. Aripiprazole was provided in 5-, 10-, or 15-mg oral tablets and administered at a starting dose of 5 mg per day for Week 1. For Weeks 2 through 3, the dose was titrated up to 10 mg per day, and for Weeks 4 through 6, the dose increased to 15 mg per day. Flexible doses of either 15 or 30 mg per day were administered for Weeks 7 through 12. If participants were unable to tolerate the dose of 15 mg per day of study drug, the dose was decreased to 10 mg per day for Weeks 7 through 12.
|
Placebo + Valproate or Lithium
n=186 Participants
Participants randomly received placebo (1:1 to study drug) as adjunctive therapy to current ongoing treatment with valproate or lithium for 12 weeks.
|
|---|---|---|
|
Change From Baseline to Week 12 in Body Mass Index (BMI) (LOCF Data Set)
|
0.0 kg/m^2
Interval 0.0 to 0.4
|
0.0 kg/m^2
Interval 0.0 to 0.3
|
Adverse Events
Aripiprazole
Placebo
Serious adverse events
| Measure |
Aripiprazole
n=180 participants at risk
|
Placebo
n=189 participants at risk
|
|---|---|---|
|
General disorders
Hyperthermia
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/180
|
0.53%
1/189
|
|
Nervous system disorders
Coma
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Depression
|
2.2%
4/180
|
1.1%
2/189
|
|
Psychiatric disorders
Psychotic disorder
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Alcohol abuse
|
0.00%
0/180
|
1.1%
2/189
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/180
|
0.53%
1/189
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/180
|
0.53%
1/189
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/180
|
0.53%
1/189
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/180
|
0.53%
1/189
|
|
Nervous system disorders
Vertebrobasilar insufficiency
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Bipolar I disorder
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Mania
|
1.1%
2/180
|
3.7%
7/189
|
|
Infections and infestations
Rhinitis
|
0.00%
0/180
|
0.53%
1/189
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.56%
1/180
|
0.00%
0/189
|
|
Psychiatric disorders
Depression suicidal
|
0.56%
1/180
|
0.00%
0/189
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/180
|
0.53%
1/189
|
|
Vascular disorders
Hypertension
|
0.00%
0/180
|
0.53%
1/189
|
|
Psychiatric disorders
Intentional drug misuse
|
0.00%
0/180
|
0.53%
1/189
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/180
|
0.53%
1/189
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/180
|
0.53%
1/189
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/180
|
0.53%
1/189
|
|
Psychiatric disorders
Suicidal ideation
|
0.56%
1/180
|
0.00%
0/189
|
Other adverse events
| Measure |
Aripiprazole
n=180 participants at risk
|
Placebo
n=189 participants at risk
|
|---|---|---|
|
Psychiatric disorders
Insomnia
|
5.6%
10/180
|
5.3%
10/189
|
|
Psychiatric disorders
Depression
|
7.8%
14/180
|
2.6%
5/189
|
|
Gastrointestinal disorders
Nausea
|
5.6%
10/180
|
2.6%
5/189
|
|
Nervous system disorders
Akathisia
|
11.1%
20/180
|
2.1%
4/189
|
|
Nervous system disorders
Headache
|
2.8%
5/180
|
5.3%
10/189
|
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