Trial Outcomes & Findings for A Trial to Evaluate the Efficacy, Safety & Tolerability of Brexpiprazole in the Maintenance Treatment of Adults With Major Depressive Disorder (NCT NCT03538691)

Last Updated: 2023-10-12

Results Overview

Relapse criteria included:At same visit, increase in Montgomery Asberg Depression Rating Scale\[MADRS\] total score(10 items, 0=no symptoms to 6=severe symptoms,total score=0 to 60)of 50% from randomization and Clinical Global Impression-Severity of Illness \[CGI-\](8-point scale of 0=not assessed to 7=most extremely ill)score ≥4,hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality(score of ≥4 on MADRS item10 of suicidality)or yes answered on question 4 or 5 of Columbia-Suicide Severity Rating Scale\[C-SSRS\](Suicidal Ideation \[SI\] has 5 questions: wish to be dead,non-specific active suicidal thoughts,active SI with any methods \[not plan\]without intent to act,active SI with some intent to act without specific plan,active SI with specific plan,intent)or yes answered to any question in suicidal behavior section (5 questions:preparatory acts/behavior,aborted attempt,interrupted attempt,actual attempt\[non-fatal\],completed suicide).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1149 participants

Primary outcome timeframe

Up to 14 days post last dose in Phase C (up to 28 weeks)

Results posted on

2023-10-12

Participant Flow

A total of 1149 participants with major depressive disorder (MDD) participated in the study from 13 July 2018 to 29 July 2022.

Of the 1149 participants enrolled in Phase A (Acute Treatment) of the study, 766 eligible participants continued to Phase B (Stabilization). Eligible participants who completed the Phase B were randomized into Phase C (Double-blind Randomized Withdrawal) to receive brexpiprazole or placebo along with open-label antidepressant therapy (ADT) in a 1:1 ratio for up to 26 weeks.

Participant milestones

Participant milestones
Measure	Phase A: Brexpiprazole + ADT Participants received brexpiprazole 2 or 3 milligrams per day (mg/day) along with protocol-specified antidepressant therapy (ADT), orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related adverse events (AEs), and had not achieved the maximum dose of medication had their dose increased up to 3 mg.	Phase B: Brexpiprazole + ADT Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.	Phase C: Brexpiprazole + ADT Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase A: Acute Treatment (up to 8 Weeks) STARTED	1149	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Phase A Safety Sample	1136	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) COMPLETED	766	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) NOT COMPLETED	383	0	0	0
Phase B: Stabilization (12 Weeks) STARTED	0	766	0	0
Phase B: Stabilization (12 Weeks) Phase B Safety Sample	0	765	0	0
Phase B: Stabilization (12 Weeks) COMPLETED	0	489	0	0
Phase B: Stabilization (12 Weeks) NOT COMPLETED	0	277	0	0
Phase C:Randomized Withdrawal (26 Weeks) STARTED	0	0	240	249
Phase C:Randomized Withdrawal (26 Weeks) Phase C Safety Sample	0	0	240	248
Phase C:Randomized Withdrawal (26 Weeks) COMPLETED	0	0	120	131
Phase C:Randomized Withdrawal (26 Weeks) NOT COMPLETED	0	0	120	118

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase A: Brexpiprazole + ADT Participants received brexpiprazole 2 or 3 milligrams per day (mg/day) along with protocol-specified antidepressant therapy (ADT), orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related adverse events (AEs), and had not achieved the maximum dose of medication had their dose increased up to 3 mg.	Phase B: Brexpiprazole + ADT Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.	Phase C: Brexpiprazole + ADT Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase A: Acute Treatment (up to 8 Weeks) Lost to Follow-up	24	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Adverse Event	82	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Subject Withdrew Consent	54	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Death	1	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Non-Compliance With Study Drug	9	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Lack of Efficacy	185	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Protocol Deviation	12	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Physician Decision	1	0	0	0
Phase A: Acute Treatment (up to 8 Weeks) Reason not Specified (not due to Coronavirus Disease 2019 [COVID-19] Restriction)	15	0	0	0
Phase B: Stabilization (12 Weeks) Lost to Follow-up	0	5	0	0
Phase B: Stabilization (12 Weeks) Adverse Event	0	52	0	0
Phase B: Stabilization (12 Weeks) Subject Withdrew Consent	0	47	0	0
Phase B: Stabilization (12 Weeks) Non-Compliance With Study Drug	0	9	0	0
Phase B: Stabilization (12 Weeks) Lack of Efficacy	0	136	0	0
Phase B: Stabilization (12 Weeks) Pregnancy	0	1	0	0
Phase B: Stabilization (12 Weeks) Protocol Deviation	0	9	0	0
Phase B: Stabilization (12 Weeks) Physician Decision	0	6	0	0
Phase B: Stabilization (12 Weeks) Due to COVID-19 Restriction	0	1	0	0
Phase B: Stabilization (12 Weeks) Reason not Specified (not due to COVID-19 Restriction)	0	11	0	0
Phase C:Randomized Withdrawal (26 Weeks) Lost to Follow-up	0	0	16	4
Phase C:Randomized Withdrawal (26 Weeks) Adverse Event	0	0	6	6
Phase C:Randomized Withdrawal (26 Weeks) Subject Withdrew Consent	0	0	6	19
Phase C:Randomized Withdrawal (26 Weeks) Non-Compliance With Study Drug	0	0	1	2
Phase C:Randomized Withdrawal (26 Weeks) Non-compliant Participants	0	0	32	28
Phase C:Randomized Withdrawal (26 Weeks) Pregnancy	0	0	1	0
Phase C:Randomized Withdrawal (26 Weeks) Lack of Efficacy (Phase C MDD Relapse)	0	0	54	52
Phase C:Randomized Withdrawal (26 Weeks) Physician Decision	0	0	0	1
Phase C:Randomized Withdrawal (26 Weeks) Reason not Specified (not due to COVID-19 Restriction)	0	0	4	6

Baseline Characteristics

A Trial to Evaluate the Efficacy, Safety & Tolerability of Brexpiprazole in the Maintenance Treatment of Adults With Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase A: Brexpiprazole + ADT n=1149 Participants Participants received brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related AEs, and had not achieved the maximum dose of medication had their dose increased up to 3 mg.
Age, Continuous	42.3 years STANDARD_DEVIATION 13.1 • n=5 Participants
Sex: Female, Male Female	734 Participants n=5 Participants
Sex: Female, Male Male	415 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	110 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	968 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	71 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	159 Participants n=5 Participants
Race (NIH/OMB) White	868 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 14 days post last dose in Phase C (up to 28 weeks)

Population: Phase C Efficacy Sample included all participants randomized to the double-blind treatment who had taken at least one dose of investigational medicinal product (IMP) in Phase C. Overall number of participants analyzed for median time to relapse is the number of participants with impending relapse.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=54 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=51 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Time-to-Relapse by Any Criteria as Defined in Blinded Addendum	63.0 days Interval 8.0 to 185.0	63.0 days Interval 8.0 to 190.0

SECONDARY outcome

Timeframe: Baseline and Week 46

Population: Phase C Efficacy Sample included all participants randomized to the double-blind treatment who had taken at least one dose of IMP in Phase C. Overall number of participants analyzed is the number of participants with data available for analyses.

The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. The SDS total score is the mean of the 3 item responses. The SDS total score ranges from 0 to 10, with higher scores indicating greater functional impairment. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. Analysis of covariance (ANCOVA) model was used for analysis.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=239 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=242 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Change From Baseline for Randomization Phase in Sheehan Disability Scale (SDS) Mean Total Score at Week 46	0.72 score on a scale Standard Error 0.18	0.48 score on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Up to 14 days post last dose in Phase C (up to 28 weeks)

Population: Phase C Efficacy Sample included all participants randomized to the double-blind treatment who had taken at least one dose of IMP in Phase C. Overall number of participants analyzed for median time to functional relapse is the number of participants with impending functional relapse.

Time-to-functional relapse was based on a 30% increase in the SDS mean total score from Phase C Baseline, at least one SDS sub-score at 4 or greater, and an SDS total score ≥7 when all 3 sub-scores were available. The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=81 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=73 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Time-to-functional Relapse Based on SDS Criteria	36.0 days Interval 6.0 to 185.0	35.0 days Interval 8.0 to 176.0

SECONDARY outcome

Timeframe: Up to 26 weeks in Phase C

Population: Phase C Efficacy Sample included all participants randomized to the double-blind treatment who had taken at least one dose of IMP in Phase C.

Relapse criteria included: At the same visit, increase in MADRS total score (10 items,7-point scale of 0=no symptoms to 6=severe symptoms, total score of 0 to 60) of 50% from randomization and CGI-S (8-point scale ranging from 0=not assessed to 7=most extremely ill) score ≥4, hospitalization for depression, discontinuation for lack of efficacy/worsening of depression, active suicidality (score of ≥4 on MADRS item 10 of suicidality) or answer of yes on question 4 or 5 of C-SSRS (SI has 5 questions: wish to be dead, non-specific active suicidal thoughts, active SI with any methods \[not plan\] without intent to act, active SI with some intent to act without specific plan, active SI with specific plan, intent) or answer of yes to any question in suicidal behavior section (5 questions: preparatory acts/behavior, aborted attempt, interrupted attempt, actual attempt \[non-fatal\], completed suicide). Percentage of participants were rounded off to single decimal point.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=240 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=248 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Percentage of Participants Meeting Any Relapse Criteria	22.5 percentage of participants	20.6 percentage of participants

SECONDARY outcome

Timeframe: Weeks 21, 23, 25, 29, 33, 37, 41, 45, and 46

Participants maintaining remission was defined as MADRS total score ≤10. The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=238 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=242 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Percentage of Participants Maintaining Remission Week 21	90.34 percentage of participants	91.3 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 29	79.89 percentage of participants	85.5 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 23	85.22 percentage of participants	82.7 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 25	84.79 percentage of participants	82.6 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 33	88.55 percentage of participants	88.4 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 37	87.92 percentage of participants	89.0 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 41	84.78 percentage of participants	89.4 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 45	88.14 percentage of participants	89.0 percentage of participants
Phase C: Percentage of Participants Maintaining Remission Week 46	90.91 percentage of participants	91.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 46

The MADRS is a clinician-rated scale to assess depressive symptomatology during the preceding week. Participants were rated on 10 items (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) each on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression. A positive change from Baseline indicates worsening of symptoms. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=240 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=247 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Change From Baseline for Randomization Phase in MADRS Total Score at Week 46	4.09 score on a scale Standard Error 0.75	4.21 score on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Baseline and Week 46

The CGI -S was used to rate the severity of illness for each participant on an 8-point scale ranging from 0 to 7 where 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. A positive change from Baseline indicates worsening of illness. Baseline was defined as the last available assessment value in Phase B for this outcome measure. ANCOVA model was used for analysis.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=240 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=247 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Change From Baseline for Randomization Phase in CGI-S Score at Week 46	0.56 score on a scale Standard Error 0.10	0.53 score on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and Week 46

The SDS is a self-rated instrument used to measure the effect of the participant's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0=not at all, to 10=extremely. Higher scores of 5 and above are associated with significant functional impairment. A positive change from Baseline indicates worsening of symptoms impacting each area. Baseline was defined as the last available assessment value between Week 14 and Week 20 in Phase B for this outcome measure. ANCOVA model was used for analysis.

Outcome measures

Outcome measures
Measure	Phase C: Brexpiprazole + ADT n=239 Participants Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=244 Participants Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46 Work/School	0.46 score on a scale Standard Error 0.22	0.31 score on a scale Standard Error 0.23
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46 Social Life	0.91 score on a scale Standard Error 0.19	0.56 score on a scale Standard Error 0.19
Phase C: Change From Baseline for Randomization Phase in Each of the SDS Individual Item Scores at Week 46 Family Life	0.78 score on a scale Standard Error 0.19	0.52 score on a scale Standard Error 0.19

Adverse Events

Phase A: Brexpiprazole + ADT

Serious events: 10 serious events

Other events: 398 other events

Deaths: 1 deaths

Phase B: Brexpiprazole + ADT

Serious events: 12 serious events

Other events: 163 other events

Deaths: 0 deaths

Phase C: Brexpiprazole + ADT

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Phase C: Placebo + ADT

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Phase A: Brexpiprazole + ADT n=1136 participants at risk Participants received brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 6 to 8 weeks during Phase A. Participants were initially titrated to a target dose of brexpiprazole 2 mg over a 2 to 4-week period. Thereafter, participants who had not met response criteria as defined in the blinded addendum, did not have potentially dose-related AEs, and had not achieved the maximum dose of medication had their dose increased up to 3 mg.	Phase B: Brexpiprazole + ADT n=765 participants at risk Eligible participants completing Phase A were enrolled in Phase B to receive brexpiprazole 2 or 3 mg/day along with protocol-specified ADT, orally, for 12 weeks.	Phase C: Brexpiprazole + ADT n=240 participants at risk Eligible participants completing Phase B received brexpiprazole 2 or 3 mg/day (dose of brexpiprazole that they were receiving at Week 20 of the Stabilization Phase) along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.	Phase C: Placebo + ADT n=248 participants at risk Eligible participants completing Phase B received brexpiprazole-matching placebo along with protocol-specified ADT, orally, for up to 26 weeks during Phase C.
Investigations Weight increased	0.00% 0/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	15.9% 122/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	10.4% 25/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	5.2% 13/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Nervous system disorders Headache	9.9% 113/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	5.4% 41/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Gastrointestinal disorders Nausea	5.6% 64/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Metabolism and nutrition disorders Increased appetite	5.3% 60/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Nervous system disorders Akathisia	9.6% 109/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Nervous system disorders Somnolence	7.9% 90/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.
Psychiatric disorders Insomnia	6.3% 72/1136 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/765 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/240 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.	0.00% 0/248 • From first dose of study drug to 21 days after the last dose (Up to 49 weeks) All-cause Mortality: Enrolled Sample included all participants who signed informed consent form and entered Phase A. Serious and Other AEs: Phase A Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase A. Phase B Safety Sample=all participants who received at least 1 dose of brexpiprazole in Phase B. Phase C Safety Sample=all participants who were randomized to double-blind treatment and received at least one dose of double-blind trial medication in Phase C.

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place