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Brexpiprazole for Bipolar Depression

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ClinicalTrials.gov Identifier: NCT03427892
Recruitment Status : Completed
First Posted : February 9, 2018
Results First Posted : March 13, 2019
Last Update Posted : March 13, 2019
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Bipolar Depression
Intervention Drug: Brexpiprazole
Enrollment 21
Recruitment Details This study enrolled patients recruited through flyers and other forms of advertisement. Patients met DSM-5 criteria for bipolar I or II disorder, with a current moderate to severe depressed mood state. The last patient completed on March 15, 2018.
Pre-assignment Details Of the 30 patients consented and screened during the duration of the study between March 2017 and December 2017, 9 screen failed and 21 were enrolled within the study. The study was non-randomized and all patients received the same study condition.
Arm/Group Title Brexpiprazole
Hide Arm/Group Description

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Period Title: Overall Study
Started [1] 21
Completed 19 [2]
Not Completed 2
Reason Not Completed
Lost to Follow-up             2
[1]
Open Label (baseline to week 8)
[2]
Of the 21 recruited, 19 completed at least one post baseline visit, included in the analysis.
Arm/Group Title Brexpiprazole
Hide Arm/Group Description

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
<=18 years
0
   0.0%
Between 18 and 65 years
19
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
38.74  (12.38)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
3
  15.8%
Male
16
  84.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Hispanic or Latino
5
  26.3%
Not Hispanic or Latino
14
  73.7%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
8
  42.1%
White
9
  47.4%
More than one race
2
  10.5%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
 100.0%
Montgomery Asberg Depression Rating Scale (MADRS) score ranges from 0-60, higher score is indicative   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 19 participants
31.95  (10.33)
[1]
Measure Description: Montgomery Asberg Depression Rating Scale (MADRS) score ranges from 0-60, higher score is indicative of more acute depressive symptoms."
1.Primary Outcome
Title The Montgomery-Asberg Depression Rating Scale (MADRS)
Hide Description The Montgomery-Asberg Depression Rating Scale is used to assess depressive symptom severity. There are 10 items and each item is rated from 0 to 6 (increasing severity) based on the assessment of symptoms within the past 7 days. Scoring is assisted by descriptive anchors that serve as useful guides at 0,2,4, 8. Odd numbers (1,3,5) between the descriptive anchors are also meant to be scored. Highest possible MADRS score is 60. Lowest possible MADRS score is 0. MADRS is scored by taking the sum of the scores for each item. A higher score is indicative of more acute depressive symptoms.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
MADRS Baseline 31.95  (10.33)
MADRS Week 4 9.95  (8.28)
MADRS Week 8 10.95  (9.59)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value <.001
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
2.Secondary Outcome
Title Young Mania Rating Scale (YMRS)
Hide Description Young Mania Rating Scale is an observer-rated measure of mania symptoms. It has 11 items and each items has 5 defined anchor points with increasing severity that describe the symptom characteristics. YMRS is scored by taking sum of the scores for the 11 items. A higher score indicative of more acute manic symptoms. Seven of the items are scored between 0 and 4. Four items allow for scoring between anchor points (ranging 1 to 8). Maximum score is 60 and minimum score is 0.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
YMRS Baseline 4.63  (3.22)
YMRS Week 4 4.21  (3.97)
YMRS Week 8 4.42  (5.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .93
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
3.Secondary Outcome
Title Rey Auditoy Verbal Learning Test
Hide Description Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. On completion of Trial 5, an interference list of 15 words (List B) is presented, followed by a free recall test of that list. After a 20-min delay, the examinee is again required to recall the words from list A - this is called the delay raw score. The raw scores on both the total recall and the delay trials (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: T-scores
RAVLT T Score Baseline 37.47  (16.67)
RAVLT T Score Week 4 37.79  (10.36)
RAVLT T Score Week 8 40.42  (11.97)
RAVLT Delay Baseline 39.74  (13.23)
RAVLT Delay Week 4 37.00  (9.010)
RAVLT Delay Week 8 39.26  (13.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .49
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor. The above reported is RAVLT Score
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .56
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.Reported is delay score
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
4.Secondary Outcome
Title Stroop Task
Hide Description The Stroop task evaluates attention, speed, and accuracy of thinking. Stroop task consists of three separate trials: word, color, and color-word (CW) naming. For each trial, a raw score (correct number of words named) is recorded. The raw score for each trial is converted to a T-score based on participant's age and education level. The possible T-scores range from 15-85 for the word trial, 8-92 for the color trial, and 3-98 for the color-word trial. The interference score (Inter) is also derived from the color-word score, with T-scores ranging from 21-80. Higher numbers indicate better performance. The entered values represent T-scores.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: T-scores
STROOP-CW Baseline 48.11  (7.39)
STROOP-CW Week 4 41.21  (34.73)
STROOP-CW Week 8 50.74  (6.82)
STROOP-Inter Baseline 49.89  (5.64)
STROOP-Inter Week 4 43.47  (34.95)
STROOP-Inter Week 8 51.79  (5.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .221
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor. Reported is CW score.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .306
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.Reported is Inter. score
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
5.Secondary Outcome
Title Trail Making Test (TMT)
Hide Description The Trail Making Test (TMT) measures attention, speed, and accuracy. TMT consists of two parts: Trails A and Trails B. The performance on each test is measured in seconds and represents how quickly a participant can connect the numbers (Trails A) and the numbers and letters (Trails B) together. The number of seconds it takes to complete each part of TMT is converted to a T-score based on gender, age, race, and education. The T-scores range from 0-100 with higher scores indicating better (faster) performance. The entered data are presented as T-Scores.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: T-scores
TMT A Score Baseline 47.74  (9.34)
TMT A Score Week 4 51.16  (11.49)
TMT A Score Week 8 53.47  (13.24)
TMT B Score Baseline 45.79  (6.39)
TMT B Score Week 4 47.37  (7.57)
TMT B Score Week 8 49.68  (11.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .07
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor. The above reported is TMT A.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .19
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.The above reported is TMT B.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
6.Secondary Outcome
Title Systematic Assessment For Treatment Emergent Events
Hide Description The Systematic Assessment for Treatment Emergent Effects (SAFTEE) is a self-report scale used in clinical trials and is designed to evaluate the degree to which each possible side effect is bothersome to a participant. There are 55 items on the scale (each item represents a different side effect), with each item rated on a 4-point scale such as "not bothersome - 0 (zero)", "mildly bothersome - 1", "moderately bothersome - 2", "severely bothersome - 3". The total possible range of scores on the scale is 0-165. The higher scores indicate a higher degree of being bothered by various side effects.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
SAFTEE Baseline 49.79  (27.74)
SAFTEE Week 4 23.53  (20.51)
SAFTEE Week 8 23.42  (22.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value <.001
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
7.Secondary Outcome
Title Columbia Suicide Severity Rating Scale
Hide Description The Columbia Suicide Severity Rating Scale (C-SSRS) is a structured interview and rating scale used to measure suicidal thoughts and behaviors. Actual attempts, interrupted attempts, and aborted attempts are measured as positive integers (zero and above). The minimum value for the actual, interrupted, and aborted attempt is zero (reflecting no past suicidal behavior). There is no maximum scale value, as the number of attempts differs for each participant. The entered values represent the average number of actual, interrupted, and aborted attempts in the group. Higher values reflect a higher number of attempts experienced by each participant (equivalent to a worse outcome).
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: attempts
C-SSRS Actual Attempts -in lifetime- Baseline 1.35  (2.43)
C-SSRS Actual Attempts-since last visit Week 4 0.00  (0.00)
C-SSRS Actual Attempts-since last visit Week 8 0.00  (0.00)
C-SSRS Interrupted Attempts-in lifetime- Baseline 0.10  (0.31)
CSSRS Interrupted Attempts-since last visit Week 4 0.00  (0.00)
CSSRS Interrupted Attempts-since last visit Week 8 0.00  (0.00)
C-SSRS Aborted Attempt-in lifetime-Baseline 0.00  (0.00)
C-SSRS Aborted Attempt-since last visit-Week 4 0.00  (0.00)
C-SSRS Aborted Attempt-since last visit-Week 8 0.00  (0.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .022
Comments To analyze separate one-way repeated measures analyses of variance (ANOVA) were performed. Time (baseline, week 4, week 8) was included as the within-subject factor.Above is from baseline to week 8 for C-SSRS AA, IA, and ABA.
Method ANOVA
Comments One-way repeated measures (ANOVA) were performed. Time (baseline, wk 4, wk 8) included as within-subject factor. Above is for C-SSRS AA,IA, and ABA.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .163
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
8.Secondary Outcome
Title Abnormal Involuntary Movement Scale
Hide Description The Abnormal Involuntary Movement Scale (AIMS) is an assessment of movements to determine any long-term drug induced movement disorders.There are 10 items on the scale with scores ranging from 0-4 (0 None/Normal, 1 minimal, 2 mild, 3 moderate,4 severe). 4 items assess facial and oral movements, 2 items measure extremity movements, 1 item measures trunk movements, and 3 items measure global judgments regarding symptoms assessed. A total score is the sum of scores for items assessing facial and oral movements, extremity movements, and trunk movement (scores ranging from 0-28), with 0 being the lowest score, and 28 being the highest score. A higher score is indicative of a higher severity in symptomatology.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
AIMS Baseline 0.63  (2.09)
AIMS Week 4 1.26  (2.23)
AIMS Week 8 1.16  (2.29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .133
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
9.Secondary Outcome
Title Barnes Akathisia Scale
Hide Description The Barnes Akathisia Scale (BAS) is an assessment of movements to determine any short-term drug-induced movement disorders. There are 5 items.Items 1-3 are rated from a scale of 0-3 with 0 indicating the least severity, and 3 indicating the highest severity of symptoms. Item 4 is a global assessment of symptoms assessed and the severity is assessed on a scale of 0-5, with 0 indication least severity and 5 indicating the most severity.The total score is the sum of all the item scores (scores ranging from 0-14).With higher scores reflecting worse outcome.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
BAS Baseline 0.12  (0.12)
BAS Week 4 2.37  (0.56)
BAS Week 8 2.47  (0.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .002
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
10.Secondary Outcome
Title Simpson Angus Scale
Hide Description The Simpson Angus Scale (SAS) measured drug-induced movement side effects. There are 10 items on the scale, with each item scored on a scale of 0-4 (least to most severe). The total possible range of scores across all items is 0-40, with higher scores indicative of worse outcome.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
SAS Baseline 0.37  (0.23)
SAS Week 4 1.16  (0.34)
SAS Week 8 1.00  (0.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .002
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
11.Secondary Outcome
Title Quality of Life in Bipolar Disorder (QOLBD)
Hide Description The Quality Of Life in Bipolar Disorder (QOLBD) is a measure of the quality of life in patients with bipolar disorder. All questions on the scale ask about a range of experiences, behaviors, and feeling related to the quality of life. For each question, a participant is asked to indicate how much they agree with each question. The scale consists of 12 questions, with each question measured on a 5-point scale, such as "strongly disagree - 1", "disagree - 2", "neutral - 3", "agree - 4", "strongly agree - 5". The total possible range of scores on the scale is 12-60. Higher scores indicate better quality of life.
Time Frame Baseline and at week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
QOLBD baseline 30.38  (8.97)
QOLBD Week 8 40.95  (11.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .005
Comments Pairwise comparisons were also performed to determine which time points were significantly different from one another. Baseline to week 8 is reported above.
Method t-test, 2 sided
Comments Pairwise comparisons were also performed to determine which time points were significantly different from one another.
12.Secondary Outcome
Title The Inventory of Depressive Symptomatology Self-Report (IDS-SR30)
Hide Description An 30 item inventory self report assessing depressive symptoms and mood, within the past seven days. With the score range of 0-90 with higher scores indicating worse outcome.
Time Frame Baseline through week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: score on a scale
IDS-SR30 Baseline 41.63  (17.50)
IDS-SR30 Week 4 18.95  (12.95)
IDS-SR30 Week 8 17.89  (16.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value <.001
Comments To analyze mood symptoms, cognitive performance, and side effects, separate one-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, and wk 8) was included as the within-subject factor.
Method ANOVA
Comments One-way repeated measures analyses of variance (ANVOA) were performed. Time (bsl, wk 4, wk8) was included as the within-subject factor.
13.Other Pre-specified Outcome
Title High Sensitivity C-Reactive Protein (Hs-CRP)
Hide Description high sensitivity C-Reactive Protein values will be used to measure inflammation
Time Frame Baseline and at week 8
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Brexpiprazole
Hide Arm/Group Description:

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

Overall Number of Participants Analyzed 19
Mean (Standard Deviation)
Unit of Measure: mg/L
hs-CRP Baseline 3.56  (8.61)
hs-CRP Week 8 3.72  (9.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole
Comments Primary Aim is to determine if brexpiprazole is associated with a reduction in depressive symptom severity in bipolar disorder outpatients. A sample size of 17 provides 80% power for a paired t-test to compare baseline to exit change scores on the MADRS of 7 (SD 10) (a more conservative change than with even the low 1 mg dose of brexpiprazole in Thase et. al. (2015)) with alpha=.05. A sample size of n=20 will allow for some early withdrawals without postbaseline data (10).
Type of Statistical Test Other
Comments Within subjects design; single group. Intent-to-treat (ITT) sample was used in the analysis, such that all participants who completed the baseline visit and at least one post-baseline assessment were included in the analysis.
Statistical Test of Hypothesis P-Value .295
Comments Pairwise comparisons were also performed to determine which time points were significantly different from one another. Baseline to week 8 is reported above.
Method t-test, 2 sided
Comments Pairwise comparisons were also performed to determine which time points were significantly different from one another.
Time Frame 8 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Brexpiprazole
Hide Arm/Group Description

Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.

Brexpiprazole: Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.

All-Cause Mortality
Brexpiprazole
Affected / at Risk (%)
Total   0/19 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole
Affected / at Risk (%) # Events
Total   0/19 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Brexpiprazole
Affected / at Risk (%) # Events
Total   9/19 (47.37%)    
Eye disorders   
Eye twitch   2/19 (10.53%)  2
Metabolism and nutrition disorders   
Weight Gain   1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders   
Jaw clenching   1/19 (5.26%)  1
Nervous system disorders   
Restlessness   2/19 (10.53%)  2
Dizziness   2/19 (10.53%)  2
Migraines   1/19 (5.26%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. E. Sherwood Brown
Organization: UTexasSouthwestern
Phone: (214) 645-6950
Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT03427892     History of Changes
Other Study ID Numbers: 102016-048
First Submitted: December 28, 2016
First Posted: February 9, 2018
Results First Submitted: November 13, 2018
Results First Posted: March 13, 2019
Last Update Posted: March 13, 2019