Trial Outcomes & Findings for Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Adults With Major Depressive Disorder and Anxiety Symptoms (NCT NCT02013531)

NCT ID: NCT02013531

Last Updated: 2016-03-29

Results Overview

The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60, with higher values indicating worse outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 37 participants
• Primary outcome timeframe: Baseline, Week 6
• Results posted on: 2016-03-29

Participant Flow

This trial was conducted in 37 participants. 18 trial sites were initiated in the United Sates, and 12 trial sites enrolled participants.

The trial consisted of a 2- to 21-day screening phase, a 6-week (42-day) treatment phase, and a 30-day (+ 2) follow-up phase.

Participant milestones

Measure	Brexpiprazole Participants were administered oral brexpiprazole tablets of 0.5 milligram per day (mg/day) with titration up to 3 mg/day once daily (QD) in addition to their constant-dose ADT (anti-depressant therapy) for 6 weeks.
Overall Study STARTED	37
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	Brexpiprazole Participants were administered oral brexpiprazole tablets of 0.5 milligram per day (mg/day) with titration up to 3 mg/day once daily (QD) in addition to their constant-dose ADT (anti-depressant therapy) for 6 weeks.
Overall Study Lost to Follow-up	3
Overall Study Met Withdrawal Criteria	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Adults With Major Depressive Disorder and Anxiety Symptoms

Baseline characteristics by cohort

Measure	Brexpiprazole n=37 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Age, Continuous	45.7 Years STANDARD_DEVIATION 15.2 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid Baseline and Post-Baseline efficacy assessment. A mixed model repeated measures (MMRM) analysis was performed.

The MADRS is utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60, with higher values indicating worse outcome.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	-19.6 Units on a scale Standard Error 1.5

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. A MMRM analysis was performed.

The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change in Clinical Global Impression-Severity (CGI-S) Total Score	-2.2 Units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: "Compared to his/her condition at baseline, how much has the participant changed?" Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 6.	1.9 Units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 1 to Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The improvement of each participants condition was rated for each participant using the CGI-I. The study physician rated the participants total improvement whether or not it was due entirely to drug treatment. To perform this assessment, the study physician answered the following question: "Compared to his/her condition at baseline, how much has the participant changed?" Response choices included: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The response at a given week was compared with the participants condition at Baseline prior to the first dose of study medication.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Percentage of Participants With CGI-I Response Rate Week 2	36.1 percentage of participants
Percentage of Participants With CGI-I Response Rate Week 1	8.3 percentage of participants
Percentage of Participants With CGI-I Response Rate Week 3	50.0 percentage of participants
Percentage of Participants With CGI-I Response Rate Week 4	66.7 percentage of participants
Percentage of Participants With CGI-I Response Rate Week 6	75.0 percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

MADRS response rate, where response is defined as ≥ 50% reduction in respective total scores from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60, higher values indicate worse outcome.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Percentage of Participants With a MADRS Response	69.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Baseline to Week 6. The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS Total Score is the sum of ratings for all 10 items. The possible Total scores are from 0 to 60, higher values indicate worse outcome.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Percentage of Participants With a MADRS Remission	47.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The HAM-D17 was utilized as an assessment of a participants level of depression and was administered utilizing the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D). Detailed instructions for administration of this structured interview were provided in the SIGH-D. The HAM-D17 was administered at the following visits: screening, Baseline, and Week 6/ Early termination (ET). HAM-D17 is a 17-item questionnaire with a total score of 0 to 52 with higher scores indicating more depressive symptoms.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Hamilton Depression Rating Scale (HAM-D17) Total Score	-15.85 Units on a scale Standard Deviation 7.37

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. A MMRM analysis was performed.

The HAM-A was utilized for the evaluation of anxiety symptoms and was administered using the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A). Detailed instructions for administration of this structured interview were provided in the SIGH-A. The HAM-A was administered at the following visits: screening, Baseline, Weeks 1, 2, 3, 4, and 6/ET. HAM-A is a 14-item scale with each item is scored on a scale from 0 (not present) to 4 (very severe) with a total score of 0 to 56, with higher scores indicating severe anxiety symptoms.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score	-17.80 Units on a scale Standard Error 1.23

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The SDS was a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. The SDS was a visual analogue scale that used spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the 3 domains. The number most representative of how much each area was disrupted by symptoms was marked along the line from 0 = not at all to 10 = extremely. Scores of 5 and above were associated with significant functional impairment. The three items may be summed into a single dimensional measure of global functional impairment that ranges from 0 (unimpaired) to 30 (highly impaired).

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Sheehan Disability Scale (SDS) Mean Score	-3.62 Units on a scale Standard Deviation 2.60

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The MGH-CPFQ was a participant-rated scale designed to assess cognitive and executive dysfunction including symptoms of fatigue in mood and anxiety disorders. The MGH-CPFQ consisted of 7 items, each rated on a scale from 1 (greater than normal functioning) to 6 (poorer than normal functioning). The total score of the 7 items ranged from 7 to 42, with higher scores indicative of a worse outcome. The MGH-CPFQ was administered at the following visits: Baseline and Week 6/ET.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score	-9.85 Units on a scale Standard Deviation 8.79

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

KSQ is a subject-rated scale designed to assess distress using symptoms of depression, anxiety, anger-hostility and somatization. The questionnaire contains 92 items of which 68 items indicate symptoms and 24 items are antonyms of some of the symptoms that indicate well-being. The maximum score for each symptom subscale is 17, the well-being subscales 6 and for the total scale scores 23. A higher score indicates more distress than a lower score. The total subscale scores will be unevaluable if less than 19 of the 23 items are recorded. If 19 to 22 of the 23 items are recorded, the total subscale score is the mean of the recorded items multiplied by 23 and then rounded to the first decimal place. The total score will be unevaluable if less than 76 of the 92 items are recorded. If 76 to 91 of the 92 items and no less than 19 of the 23 items of each subscale are recorded, the total score will be the mean of the recorded items multiplied by 92 and then rounded to the first decimal place.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Kellner Symptom Questionnaire (KSQ)	-29.43 Units on a scale Standard Deviation 20.88

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET.

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Go/No-Go Task for P-inhibition Failures P-inhibition failures (Go cues)	-0.0193 failures Standard Deviation 0.2324
Mean Change From Baseline in Go/No-Go Task for P-inhibition Failures P-inhibition failures (No-Go cues)	-0.0103 failures Standard Deviation 0.2337

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Executive function and working memory were assessed for the Go/No-go Task using computer-based and paper-pencil neuropsychological instruments. These instruments focused on measuring impulse inhibition. The instrument was administered at the following visits: Baseline and Week 6/ET.

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Go/No-Go Task for Mean Reaction Time Mean reaction time (No-Go cues)	-4.26 milliseconds Standard Deviation 51.69
Mean Change From Baseline in Go/No-Go Task for Mean Reaction Time Mean reaction time (Go cues)	-0.26 milliseconds Standard Deviation 52.49

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Delay discounting was a participant-completed task is an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consists of 27 choices between immediate and delayed rewards. The participant chooses repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (for example, "would you prefer $27 today or $50 in 21 days?") The answers provide an estimate of the participant's discounting rate; higher discounting rates indicate greater impulsivity. A total score is not computed for all 27 questions.

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) Score	-0.008442 unitless Standard Deviation 0.060200

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The experiential discounting task (EDT) was a subject-completed computerized task designed to measure delay discounting, an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The participant chose between different amounts of money available at different delays or with different chances (probability to get the money). At the end of the session, one of the choices was selected at random, and the participant received whatever they chose in response of that question (immediate, delayed, or probabilistic amount). Formula for h-value: value = A / (1 + hO) p is probability of reward and O is odds against. The value of h indicates how the value of a reward and the probability of its occurrence decreases. The data are computerized and reflect delay discounting and impulsivity (higher discounting and higher probability discounting shows greater impulsivity). A total score is not computed for this task.

Outcome measures

Measure	Brexpiprazole n=29 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Delay and Probability Discounting Task (DPDT) Scores Delay discounting task k value	-3.586888 unitless Standard Deviation 15.156644
Mean Change From Baseline in Delay and Probability Discounting Task (DPDT) Scores Probability discouting task h value	3.505900 unitless Standard Deviation 28.036537

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Delay discounting was a participant-completed task considered as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. During a training session, a single button with letter A or B appeared on the screen. The participant had to wait until the letter began to flash, and press the button only once. An amount of money was added to a counter and another single button appeared. During the test session, both buttons with letters A and B appeared on the screen. The participant had to choose one of the letters that remained; the other disappeared. The participant had to wait until the letter began to flash and then press the button again. An amount of money was added to the counter, and both letters appeared again. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). A total score was not calculated for this task.

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline to Week 6 in the Number of Impulsive Choices in the Delayed Reward Task (DRT)	4.6 Number of Impulsive Choices Standard Deviation 18.1

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chooses between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for food is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the "X-axis" is "days", "Y-axis" is "Food value", the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting).

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Food Delay Discounting Task	0.0371 unitless Standard Deviation 0.1819

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

Delay discounting was a participant-completed task considered as an index of impulsive behavior. The participant chose between a reward they could have today and another that they could get after a specified amount of time. The participant would not receive the rewards, but was asked to make decisions as though he or she were really going to receive them. AUC is defined as area under the concentration-time curve; AUC for money is presented below. The data are computerized and reflect delay discounting and impulsivity (higher discounting shows greater impulsivity). To calculate the AUC, the "X-axis" is "days", "Y-axis" is "Money value", the actual area underneath the curve was calculated by summing the results for each delay and present value pair: x2 -x1[(y1 + y2)/2], where x1 and x2 are successive delays and y1 and y2 are the present values associated with those delays. The AUC can range from 1 (no discounting) to 0 (maximum discounting).

Outcome measures

Measure	Brexpiprazole n=35 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Money Delay Discounting Task	0.0707 unitless Standard Deviation 0.2284

SECONDARY outcome

Timeframe: Baseline, Week 6

Population: Participants took at least 1 dose of brexpiprazole and who had a valid baseline assessment and Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, if no observation is recorded at that visit, data carried forward from the previous scheduled treatment phase visit.

The BIS-11 was a participant-rated scale designed to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). The scores provided information to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and 3 second-order factors (motor impulsiveness, non-planning impulsiveness, and attentional impulsiveness). The total score ranged from 30 to 120, with higher scores indicating impulsive personality traits. The BIS-11 was administered at the following visits: Baseline and Week 6/ET.

Outcome measures

Measure	Brexpiprazole n=36 Participants Participants were administered oral brexpiprazole tablets of 0.5 mg/day with titration up to 3 mg/day QD in addition to their constant-dose ADT for 6 weeks.
Mean Change From Baseline in Barratt Impulsiveness Scale 11-item (BIS-11) Total Score	-7.67 Units on a scale Standard Deviation 10.14

Adverse Events

Brexpiprazole

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brexpiprazole n=37 participants at risk Participants were administered oral brexpiprazole tablets of 0.5 mg/day to 3 mg/day, QD for 6 weeks.
Infections and infestations Pneumonia	2.7% 1/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).

Other adverse events

Measure	Brexpiprazole n=37 participants at risk Participants were administered oral brexpiprazole tablets of 0.5 mg/day to 3 mg/day, QD for 6 weeks.
Gastrointestinal disorders Diarrhoea	10.8% 4/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Gastrointestinal disorders Dry mouth	10.8% 4/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
General disorders Fatigue	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Infections and infestations Influenza	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Metabolism and nutrition disorders Increased appetite	13.5% 5/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	8.1% 3/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Musculoskeletal and connective tissue disorders Neck pain	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Nervous system disorders Akathisia	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Nervous system disorders Dizziness	10.8% 4/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Nervous system disorders Headache	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Nervous system disorders Paraesthesia	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Psychiatric disorders Insomnia	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Psychiatric disorders Irritability	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).
Psychiatric disorders Restlessness	5.4% 2/37 • Adverse events were reported from the signing of the informed consent until the follow-up visit of 30 (+2 days).

Additional Information

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Results disclosure agreements

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