Trial Outcomes & Findings for Brexpiprazole for Bipolar Depression (NCT NCT03427892)

NCT ID: NCT03427892

Last Updated: 2019-03-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

21 participants

Primary outcome timeframe

Baseline through week 8

Results posted on

2019-03-13

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
Brexpiprazole
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 Study
STARTED
21
Overall Study
COMPLETED
19
Overall Study
NOT COMPLETED
2

Reasons for withdrawal

Reasons for withdrawal
Measure
Brexpiprazole
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 Study
Lost to Follow-up
2

Baseline Characteristics

Brexpiprazole for Bipolar Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Brexpiprazole
n=19 Participants
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.
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
19 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Age, Continuous
38.74 years
STANDARD_DEVIATION 12.38 • n=5 Participants
Sex: Female, Male
Female
3 Participants
n=5 Participants
Sex: Female, Male
Male
16 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
14 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
8 Participants
n=5 Participants
Race (NIH/OMB)
White
9 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
2 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
19 Participants
n=5 Participants
Montgomery Asberg Depression Rating Scale (MADRS) score ranges from 0-60, higher score is indicative
31.95 units on a scale
STANDARD_DEVIATION 10.33 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
The Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS Baseline
31.95 score on a scale
Standard Deviation 10.33
The Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS Week 4
9.95 score on a scale
Standard Deviation 8.28
The Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS Week 8
10.95 score on a scale
Standard Deviation 9.59

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Young Mania Rating Scale (YMRS)
YMRS Baseline
4.63 score on a scale
Standard Deviation 3.22
Young Mania Rating Scale (YMRS)
YMRS Week 4
4.21 score on a scale
Standard Deviation 3.97
Young Mania Rating Scale (YMRS)
YMRS Week 8
4.42 score on a scale
Standard Deviation 5.36

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Rey Auditoy Verbal Learning Test
RAVLT T Score Baseline
37.47 T-scores
Standard Deviation 16.67
Rey Auditoy Verbal Learning Test
RAVLT T Score Week 4
37.79 T-scores
Standard Deviation 10.36
Rey Auditoy Verbal Learning Test
RAVLT T Score Week 8
40.42 T-scores
Standard Deviation 11.97
Rey Auditoy Verbal Learning Test
RAVLT Delay Baseline
39.74 T-scores
Standard Deviation 13.23
Rey Auditoy Verbal Learning Test
RAVLT Delay Week 4
37.00 T-scores
Standard Deviation 9.010
Rey Auditoy Verbal Learning Test
RAVLT Delay Week 8
39.26 T-scores
Standard Deviation 13.14

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Stroop Task
STROOP-CW Baseline
48.11 T-scores
Standard Deviation 7.39
Stroop Task
STROOP-CW Week 4
41.21 T-scores
Standard Deviation 34.73
Stroop Task
STROOP-CW Week 8
50.74 T-scores
Standard Deviation 6.82
Stroop Task
STROOP-Inter Baseline
49.89 T-scores
Standard Deviation 5.64
Stroop Task
STROOP-Inter Week 4
43.47 T-scores
Standard Deviation 34.95
Stroop Task
STROOP-Inter Week 8
51.79 T-scores
Standard Deviation 5.06

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Trail Making Test (TMT)
TMT B Score Week 8
49.68 T-scores
Standard Deviation 11.48
Trail Making Test (TMT)
TMT A Score Week 8
53.47 T-scores
Standard Deviation 13.24
Trail Making Test (TMT)
TMT B Score Baseline
45.79 T-scores
Standard Deviation 6.39
Trail Making Test (TMT)
TMT B Score Week 4
47.37 T-scores
Standard Deviation 7.57
Trail Making Test (TMT)
TMT A Score Baseline
47.74 T-scores
Standard Deviation 9.34
Trail Making Test (TMT)
TMT A Score Week 4
51.16 T-scores
Standard Deviation 11.49

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Systematic Assessment For Treatment Emergent Events
SAFTEE Baseline
49.79 score on a scale
Standard Deviation 27.74
Systematic Assessment For Treatment Emergent Events
SAFTEE Week 4
23.53 score on a scale
Standard Deviation 20.51
Systematic Assessment For Treatment Emergent Events
SAFTEE Week 8
23.42 score on a scale
Standard Deviation 22.24

SECONDARY outcome

Timeframe: Baseline through week 8

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).

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Columbia Suicide Severity Rating Scale
C-SSRS Actual Attempts -in lifetime- Baseline
1.35 attempts
Standard Deviation 2.43
Columbia Suicide Severity Rating Scale
C-SSRS Actual Attempts-since last visit Week 4
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
C-SSRS Actual Attempts-since last visit Week 8
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
C-SSRS Interrupted Attempts-in lifetime- Baseline
0.10 attempts
Standard Deviation 0.31
Columbia Suicide Severity Rating Scale
CSSRS Interrupted Attempts-since last visit Week 4
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
CSSRS Interrupted Attempts-since last visit Week 8
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
C-SSRS Aborted Attempt-in lifetime-Baseline
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
C-SSRS Aborted Attempt-since last visit-Week 4
0.00 attempts
Standard Deviation 0.00
Columbia Suicide Severity Rating Scale
C-SSRS Aborted Attempt-since last visit-Week 8
0.00 attempts
Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Abnormal Involuntary Movement Scale
AIMS Baseline
0.63 score on a scale
Standard Deviation 2.09
Abnormal Involuntary Movement Scale
AIMS Week 4
1.26 score on a scale
Standard Deviation 2.23
Abnormal Involuntary Movement Scale
AIMS Week 8
1.16 score on a scale
Standard Deviation 2.29

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Barnes Akathisia Scale
BAS Baseline
0.12 score on a scale
Standard Deviation 0.12
Barnes Akathisia Scale
BAS Week 4
2.37 score on a scale
Standard Deviation 0.56
Barnes Akathisia Scale
BAS Week 8
2.47 score on a scale
Standard Deviation 0.57

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Simpson Angus Scale
SAS Baseline
0.37 score on a scale
Standard Deviation 0.23
Simpson Angus Scale
SAS Week 4
1.16 score on a scale
Standard Deviation 0.34
Simpson Angus Scale
SAS Week 8
1.00 score on a scale
Standard Deviation 0.32

SECONDARY outcome

Timeframe: Baseline and at week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
Quality of Life in Bipolar Disorder (QOLBD)
QOLBD baseline
30.38 score on a scale
Standard Deviation 8.97
Quality of Life in Bipolar Disorder (QOLBD)
QOLBD Week 8
40.95 score on a scale
Standard Deviation 11.03

SECONDARY outcome

Timeframe: Baseline through week 8

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
The Inventory of Depressive Symptomatology Self-Report (IDS-SR30)
IDS-SR30 Baseline
41.63 score on a scale
Standard Deviation 17.50
The Inventory of Depressive Symptomatology Self-Report (IDS-SR30)
IDS-SR30 Week 4
18.95 score on a scale
Standard Deviation 12.95
The Inventory of Depressive Symptomatology Self-Report (IDS-SR30)
IDS-SR30 Week 8
17.89 score on a scale
Standard Deviation 16.19

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and at week 8

high sensitivity C-Reactive Protein values will be used to measure inflammation

Outcome measures

Outcome measures
Measure
Brexpiprazole
n=19 Participants
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.
High Sensitivity C-Reactive Protein (Hs-CRP)
hs-CRP Baseline
3.56 mg/L
Standard Deviation 8.61
High Sensitivity C-Reactive Protein (Hs-CRP)
hs-CRP Week 8
3.72 mg/L
Standard Deviation 9.56

Adverse Events

Brexpiprazole

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Brexpiprazole
n=19 participants at risk
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.
Nervous system disorders
Restlessness
10.5%
2/19 • Number of events 2 • 8 weeks
Eye disorders
Eye twitch
10.5%
2/19 • Number of events 2 • 8 weeks
Nervous system disorders
Dizziness
10.5%
2/19 • Number of events 2 • 8 weeks
Musculoskeletal and connective tissue disorders
Jaw clenching
5.3%
1/19 • Number of events 1 • 8 weeks
Metabolism and nutrition disorders
Weight Gain
5.3%
1/19 • Number of events 1 • 8 weeks
Nervous system disorders
Migraines
5.3%
1/19 • Number of events 1 • 8 weeks

Additional Information

Dr. E. Sherwood Brown

UTexasSouthwestern

Phone: (214) 645-6950

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place