Trial Outcomes & Findings for Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Active Adults, 18 to 35 Years Old, With Major Depressive Disorder Who Are in a School or Work Environment (NCT NCT02013609)

NCT ID: NCT02013609

Last Updated: 2016-03-29

Results Overview

The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). Detailed instructions for administration of this structured interview was provided in the SIGMA. 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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 48 participants
• Primary outcome timeframe: Baseline and Week 12
• Results posted on: 2016-03-29

Participant Flow

This trial was conducted in 48 participants at 24 sites in the United States; 15 of the 24 trial sites enrolled participants.

The trial consisted of a 2 to 21-day screening phase, a 12-week (84-day) treatment phase, and a 30-day (+ 2) follow-up phase.

Participant milestones

Measure	Brexpiprazole Participants were administered oral brexpiprazole tablet of 0.5 milligram per day (mg/day) for the first week with titration up to 3 mg/day once daily (QD) in addition to their constant-dose antidepressant therapy (ADT) for 12 weeks.
Overall Study STARTED	47
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Measure	Brexpiprazole Participants were administered oral brexpiprazole tablet of 0.5 milligram per day (mg/day) for the first week with titration up to 3 mg/day once daily (QD) in addition to their constant-dose antidepressant therapy (ADT) for 12 weeks.
Overall Study Withdrawal by Subject	9
Overall Study Lost to Follow-up	3
Overall Study Adverse Event	3
Overall Study Met Withdrawal Criteria	3

Baseline Characteristics

Brexpiprazole (OPC-34712) as an Adjunctive Treatment in Active Adults, 18 to 35 Years Old, With Major Depressive Disorder Who Are in a School or Work Environment

Baseline characteristics by cohort

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Age, Continuous	26.6 Years STANDARD_DEVIATION 4.9 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment.

The MADRS was utilized as the primary efficacy assessment of the participant's level of depression and was administered utilizing the Structured Interview Guide for the MADRS (SIGMA). Detailed instructions for administration of this structured interview was provided in the SIGMA. 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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score	-18.1 Units on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment.

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=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Clinical Global Impression-Severity (CGI-S) Total Score	-2.0 Units on a scale Standard Error 0.2

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 5, 6, 8, 10 and 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment; the last-observation-carried-forward (LOCF) dataset included data recorded at a scheduled visit or, data was carried forward from the previous scheduled visit, if no observation was recorded at that 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=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 1 (N= 46)	3.5 Units on a scale Standard Deviation 0.8
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 2 (N= 47)	3.0 Units on a scale Standard Deviation 0.8
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 3 (N= 47)	2.8 Units on a scale Standard Deviation 1.0
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 4 (N= 47)	2.7 Units on a scale Standard Deviation 1.0
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 6 (N= 47)	2.6 Units on a scale Standard Deviation 1.3
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 8 (N= 47)	2.5 Units on a scale Standard Deviation 1.2
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 10 (N= 47)	2.3 Units on a scale Standard Deviation 1.2
Mean Clinical Global Impression-Improvement (CGI-I) Score at Week 12 Week 12 (N= 47)	2.2 Units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Weeks 1, 2, 3, 4, 6, 8 ,10 and 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment; the last-observation-carried-forward (LOCF) dataset included data recorded at a scheduled visit or, data was carried forward from the previous scheduled visit, if no observation was recorded at that visit

The CGI-I response rate was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Number of Participants With CGI-I Response Week 1 (N= 46)	4 participants
Number of Participants With CGI-I Response Week 2 (N= 47)	12 participants
Number of Participants With CGI-I Response Week 3 (N= 47)	17 participants
Number of Participants With CGI-I Response Week 4 (N= 47)	24 participants
Number of Participants With CGI-I Response Week 6 (N= 47)	27 participants
Number of Participants With CGI-I Response Week 8 (N= 47)	29 participants
Number of Participants With CGI-I Response Week 10 (N= 47)	28 participants
Number of Participants With CGI-I Response Week 12 (N= 47)	30 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

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

MADRS response rate was defined as ≥ 50% reduction in respective total scores from Baseline to Week 12.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Percentage of Participants With MADRS Response	53.2 percentage of particpants

SECONDARY outcome

Timeframe: Baseline and Week 12

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

MADRS remission rate, where remission is defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score from Baseline to Week 12.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Percentage of Participants With MADRS Remission	42.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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. 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=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Hamilton Depression Rating Scale (HAM-D17) Total Score	-14.9 Units on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) 3-item Total/Summed Score	-3.74 Units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) Single Item Sub-scores Work/ school	-3.5 Units on a scale Standard Error 0.5
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) Single Item Sub-scores Social life	-3.9 Units on a scale Standard Error 0.6
Mean Change From Baseline to Week 12 in Sheehan Disability Scale (SDS) Single Item Sub-scores Family life/ home responsibilities	-3.7 Units on a scale Standard Error 5.0

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

The SASS was a self-rated instrument to assess the social motivation and behavior in participants with depression. It contained 21 items covering the different aspects of social interactions, global social attitude, and self-perception. The SASS total score will be un-evaluable if less than 16 of the 20 items (for item number 1 and item number 2, participant is to answer either one of these) are recorded. If 16 to 19 of the 20 items are recorded, the SASS total score will be the mean of the recorded items multiplied by 20 and then rounded to the first decimal place.Each item is scored from 0 to 3, corresponding to minimal and maximal social adjustment, with a total score range of 0 to 60 (higher scores, indicating worse outcome).

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Social Adaptation Self-evaluation Scale (SASS) Total Score	9.7 Units on a scale Standard Error 1.6

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Massachusetts General Hospital-Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total Score	-8.1 Units on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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.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. A higher score indicates more distress than a lower score.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Kellner Symptom Questionnaire (KSQ) Total Score	-30.5 Units on a scale Standard Error 3.6

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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. Proportions of inhibitory failures (p-inhibitory failures) is measured as the proportion of no-go targets in the go-cue condition in which a participant failed to inhibit a response.

Outcome measures

Measure	Brexpiprazole n=45 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Go/No-Go Task (P-inhibition Failure) P-inhibition failures (Go cues)	0.052 failures Standard Deviation 0.299
Mean Change From Baseline to Week 12 in Go/No-Go Task (P-inhibition Failure) P-inhibition failures (No-Go cues)	0.052 failures Standard Deviation 0.295

SECONDARY outcome

Timeframe: Baseline and Week 12

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

Outcome measures

Measure	Brexpiprazole n=45 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Go/No-Go Task (Mean Reaction Time) Mean reaction time (Go cues)	-17.35 milliseconds Standard Deviation 73.34
Mean Change From Baseline to Week 12 in Go/No-Go Task (Mean Reaction Time) Mean reaction time (No-Go cues)	-12.99 milliseconds Standard Deviation 70.67

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline in Delay Discounting Task - Monetary Choice Questionnaire (MCQ) k Value	0.009531 unitless Standard Deviation 0.055516

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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=37 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in the Number of Impulsive Choices in the Delayed Reward Task (DRT)	3.6 Number of Impulsive Choices Standard Deviation 15.2

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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=41 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Delay and Probability Discounting Task (DPDT) Delay Discounting Task k value	21.315241 unitless Standard Deviation 116.798133
Mean Change From Baseline to Week 12 in Delay and Probability Discounting Task (DPDT) Delay Discounting Task h value	10.350419 unitless Standard Deviation 60.212518

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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=30 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline in Food Delay Discounting Task (DDT)	0.3487 unitless Standard Deviation 1.4158

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants who took at least 1 dose of brexpiprazole with a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. The LOCF data set included data recorded at a scheduled treatment phase visit or, data was carried forward from the previous scheduled treatment phase visit, if no observation was recorded at that 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=30 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline in Money Delay Discounting Task	-0.0095 unitless Standard Deviation 0.1859

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All participants who took at least one dose of brexpiprazole and who had a valid Baseline assessment and at least one valid Post-Baseline efficacy assessment. Mixed model repeated measures was performed on the OC dataset.

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.

Outcome measures

Measure	Brexpiprazole n=47 Participants Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Mean Change From Baseline to Week 12 in Barratt Impulsiveness Scale 11-Item (BIS-11) Total Score	-7.1 Units on a scale Standard Error 1.5

Adverse Events

Brexpiprazole

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Brexpiprazole n=47 participants at risk Participants were administered oral brexpiprazole tablet of 0.5 mg/day for the first week with titration up to 3 mg/day QD in addition to their constant-dose ADT for 12 weeks.
Gastrointestinal disorders Abdominal Discomfort	6.4% 3/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Gastrointestinal disorders Diarrhoea	8.5% 4/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Gastrointestinal disorders Nausea	10.6% 5/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Investigations Weight increased	17.0% 8/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Metabolism and nutrition disorders Increased appetite	6.4% 3/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Nervous system disorders Akathisia	6.4% 3/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Nervous system disorders Dizziness	8.5% 4/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Nervous system disorders Headache	21.3% 10/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Nervous system disorders Sedation	8.5% 4/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Nervous system disorders Somnolence	17.0% 8/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Psychiatric disorders Anxiety	12.8% 6/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Psychiatric disorders Depression	6.4% 3/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Psychiatric disorders Insomnia	10.6% 5/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.
Psychiatric disorders Libido decreased	6.4% 3/47 • Adverse events were reported from the signing of the informed consent until the last dose of brexpiprazole with a safety follow-up of 30 (+2) days. One participant out of 48 participants enrolled had discontinued before receiving study medication.

Additional Information

Global Medical Affairs

Otsuka Pharmaceutical Development and Commercialization, Inc.

Phone: 800 562-3974

Results disclosure agreements

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