Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial of the Safety and Efficacy of Two Fixed Doses of OPDC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Polaris Trial

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01360632

Acronym

Polaris

Enrollment

1539

Registered

2011-05-25

Start date

2011-06-30

Completion date

2013-09-30

Last updated

2016-01-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression, Depressive Disorder, Depressive Disorder, Major, Mental Disorders, Mood Disorders

Keywords

OPC-34712, brexpiprazole, Major Depressive Disorder, Adjunctive Treatment

Brief summary

To compare the effect of OPC-34712 (brexpiprazole) to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT

Interventions

DRUGOPC-34712 + ADT

Tablets, Oral, 1 or 3 mg OPC-34712 and FDA Approved Antidepressant Therapy (ADT)

DRUGPlacebo + ADT

Placebo + FDA Approved Antidepressant (ADT)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria * The current depressive episode must be equal to or greater than 8 weeks in duration * Subjects must report a history for the current depressive episode of an inadequate response to no more than three adequate antidepressant treatments

Exclusion criteria

* Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug * Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration * Subjects with a current Axis I (DSM-IV-TR) diagnosis of: Delirium, dementia, amnestic or other cognitive disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder * Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set	Baseline and Week 14	The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol	Baseline and Week 14	The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.

Secondary

Measure	Time frame	Description
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 11 and Week 14	The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. 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. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 11 and Week 14	The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. 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. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Week 11 and Week 14	The SDS is a self-rated instrument used to measure the effect of the patient'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. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Week 11 and Week 14	The SDS is a self-rated instrument used to measure the effect of the patient'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. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Weeks 8, 9, 10, 11, 12,13 and 14	The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician had to answer 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.
Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Weeks 8, 9, 10, 11, 12, 13, and 14	The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician had to answer 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.
Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Weeks 8, 9, 10, 11, 12, 13, and 14	IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms and atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items were not included in the calculation of the total score. The IDS-SR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDS-SR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.
Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Weeks 8, 9, 10, 11, 12, 13, and 14	The IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items were not included in the calculation of the total score. The IDSSR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDS-SR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set	Baseline and Week 14	The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52, with higher scores indicating more severe depression.
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol	Baseline and Week 14	The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52, with higher score indicating more severe depression.
Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 8, 9, 10, 11, 12, and 13	The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol	Baseline and Week 14	The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the best rating and 4 is the worst rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher score indicating worse anxiety symptoms.
Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 8 to Week 14	The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. 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.
Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Weeks 8, 9, 10, 11, 12, 13, and 14	The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. 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.
Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Weeks 8, 9, 10, 11, 12, 13, and 14	MADRS response was defined as \>=50 percent reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Weeks 8, 9, 10, 11, 12, 13, and 14	MADRS response was defined as \>=50 percent reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Weeks 8, 9, 10, 11, 12, 13 and 14	MADRS remission was defined as a \< or equal to 10 and \> or equal to 50% reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Weeks 8, 9, 10, 11, 12, 13 and 14	MADRS remission was defined as a \< or equal to 10 and \> or equal to 50% reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.
Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Weeks 8, 9, 10, 11, 12, 13 and 14	A CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Weeks, 8, 9, 10, 11, 12, 13, and 14	A CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set	Baseline and Week 14	The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the best rating and 4 is the worst rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher scores indicating worse anxiety symptoms.
Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 8, 9, 10, 11, 12, and 13	The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.

Countries

Canada, Germany, Hungary, Romania, Russia, Ukraine, United States

Participant flow

Recruitment details

The study was conducted in 1539 participants at 92 trial sites in 7 countries. United States, Germany, Ukraine, Russia, Hungary, Canada, and Romania.

Pre-assignment details

The study consisted of a 7 to 28-day Screening period, an 8-Week single-blind placebo + ADT prospective Phase-A, a 6-Week double-blind randomization Phase-B or single-blind Phase A+ and a Follow-up of 30 (+2) days after the last dose of study medication.

Participants by arm

Arm	Count
Brexpiprazole (1mg + ADT) Participants were administered brexpiprazole of 1mg as an adjunctive therapy to an assigned open-label ADT.	226
Brexpiprazole (3mg + ADT) Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.	230
Placebo + ADT Participants were administered placebo as an adjunctive therapy to an open label ADT.	221
Total	677

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Phase A+	Adverse Event	0	0	0	0	2
Phase A+	Lost to Follow-up	0	0	0	0	2
Phase A+	Met Withdrawal Criteria	0	0	0	0	7
Phase A+	Physician Decision	0	0	0	0	3
Phase A+	Protocol Deviation	0	0	0	0	3
Phase A+	Withdrawal by Subject	0	0	0	0	8
Phase A (8 Weeks)	Adverse Event	60	0	0	0	0
Phase A (8 Weeks)	Lost to Follow-up	27	0	0	0	0
Phase A (8 Weeks)	Met Withdrawal Criteria	45	0	0	0	0
Phase A (8 Weeks)	Physician Decision	10	0	0	0	0
Phase A (8 Weeks)	Protocol Deviation	39	0	0	0	0
Phase A (8 Weeks)	Withdrawal by Subject	74	0	0	0	0
Phase B (6 Weeks)	Adverse Event	0	3	9	3	0
Phase B (6 Weeks)	Lack of Efficacy	0	1	0	0	0
Phase B (6 Weeks)	Lost to Follow-up	0	1	1	0	0
Phase B (6 Weeks)	Met Withdrawal Criteria	0	0	2	1	0
Phase B (6 Weeks)	Physician Decision	0	0	0	1	0
Phase B (6 Weeks)	Protocol Deviation	0	1	4	1	0
Phase B (6 Weeks)	Withdrawal by Subject	0	4	4	7	0

Baseline characteristics

Characteristic	Brexpiprazole (1mg + ADT)	Brexpiprazole (3mg + ADT)	Placebo + ADT	Total
Age, Continuous	45.7 Years STANDARD_DEVIATION 11.6	44.5 Years STANDARD_DEVIATION 11.2	46.6 Years STANDARD_DEVIATION 11	45.6 Years STANDARD_DEVIATION 11.3
Sex: Female, Male Female	158 Participants	156 Participants	146 Participants	460 Participants
Sex: Female, Male Male	68 Participants	74 Participants	75 Participants	217 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	63 / 226	72 / 229	29 / 220
serious Total, serious adverse events	1 / 226	1 / 229	0 / 220

Outcome results

Primary

Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set

The MADRS was utilized as the primary efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.

Time frame: Baseline and Week 14

Population: The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set	-7.65 Units on a scale	Standard Error 0.5
Brexpiprazole (3mg) + ADT	Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set	-7.98 Units on a scale	Standard Error 0.51
Placebo + ADT	Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set	-6.45 Units on a scale	Standard Error 0.51

Comparison: The primary analysis was performed on the Efficacy Sample by fitting a Mixed Model Repeated Measures (MMRM) analysis with an unstructured variance covariance structure in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included fixed class effect terms for treatment, trial site, visit week, and an interaction term of treatment by visit week.p-value: 0.092595% CI: [-2.58, 0.2]Mixed Models Analysis

Comparison: The primary analysis was performed on the Efficacy Sample by fitting a MMRM analysis with an unstructured variance covariance structure in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included fixed class effect terms for treatment, trial site, visit week, and an interaction term of treatment by visit week.p-value: 0.032795% CI: [-2.92, -0.13]Mixed Models Analysis

Primary

Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol

Time frame: Baseline and Week 14

Population: Analysis was based on all participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol	-7.64 Units on a scale	Standard Error 0.52
Brexpiprazole (3mg) + ADT	Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol	-8.29 Units on a scale	Standard Error 0.53
Placebo + ADT	Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol	6.33 Units on a scale	Standard Error 0.53

Comparison: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.073795% CI: [-2.73, 0.13]Mixed Models Analysis

Comparison: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.007995% CI: [-3.39, -0.51]Mixed Models Analysis

Secondary

Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set

The SDS is a self-rated instrument used to measure the effect of the patient'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. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.

Time frame: Week 11 and Week 14

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 14	-1.16 Units on a scale	Standard Error 0.17
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 11	-1.14 Units on a scale	Standard Error 0.14
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 14	-1.35 Units on a scale	Standard Error 0.15
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 11	-1.00 Units on a scale	Standard Error 0.16
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 11	-1.13 Units on a scale	Standard Error 0.14
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 14	-1.39 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 11	-0.76 Units on a scale	Standard Error 0.14
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 14	-1.31 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 14	-0.91 Units on a scale	Standard Error 0.18
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 14	-1.28 Units on a scale	Standard Error 0.16
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 11	-0.74 Units on a scale	Standard Error 0.14
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 11	-0.18 Units on a scale	Standard Error 0.18
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 14	-0.80 Units on a scale	Standard Error 0.15
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 14	-0.73 Units on a scale	Standard Error 0.17
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Family life: Week 11	-0.51 Units on a scale	Standard Error 0.12
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 11	-0.72 Units on a scale	Standard Error 0.14
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Work/school: Week 11	-0.55 Units on a scale	Standard Error 0.15
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set	Social life: Week 14	-0.91 Units on a scale	Standard Error 0.15

Comparison: For Item: Work/School: Week 11p-value: 0.037795% CI: [-0.88, -0.03]Mixed Models Analysis

Comparison: For Item: Work/School: Week 14p-value: 0.074195% CI: [-0.91, 0.04]Mixed Models Analysis

Comparison: For Item: Work/School: Week 11p-value: 0.096695% CI: [-0.07, 0.81]Mixed Models Analysis

Comparison: For Item: Work/School: Week 14p-value: 0.477495% CI: [-0.66, 0.31]Mixed Models Analysis

Comparison: Social life: Week 11p-value: 0.026395% CI: [-0.76, -0.05]Mixed Models Analysis

Comparison: Social life: Week 14p-value: 0.021495% CI: [-0.89, -0.07]Mixed Models Analysis

Comparison: Social life: Week 11p-value: 0.828195% CI: [-0.4, 0.32]Mixed Models Analysis

Comparison: Social life: Week 14p-value: 0.05495% CI: [-0.8, 0.01]Mixed Models Analysis

Comparison: Family life: Week 11p-value: 0.000895% CI: [-0.99, -0.26]Mixed Models Analysis

Comparison: Family life: Week 14p-value: 0.009395% CI: [-0.97, -0.14]Mixed Models Analysis

Comparison: Family life: Week 11p-value: 0.218295% CI: [-0.59, 0.14]Mixed Models Analysis

Comparison: Family life: Week 14p-value: 0.025695% CI: [-0.9, -0.06]Mixed Models Analysis

Secondary

Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol

Time frame: Week 11 and Week 14

Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 14	-1.34 Units on a scale	Standard Error 0.16
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 11	-1.17 Units on a scale	Standard Error 0.14
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 14	-1.32 Units on a scale	Standard Error 0.16
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 14	-1.11 Units on a scale	Standard Error 0.2
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 11	-1.01 Units on a scale	Standard Error 0.18
Brexpiprazole (1mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 11	-1.11 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 14	-1.37 Units on a scale	Standard Error 0.16
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 14	-0.93 Units on a scale	Standard Error 0.21
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 11	-0.89 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 11	-0.20 Units on a scale	Standard Error 0.2
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 11	-0.82 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 14	-1.39 Units on a scale	Standard Error 0.16
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 14	-0.81 Units on a scale	Standard Error 0.16
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 14	-0.88 Units on a scale	Standard Error 0.17
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 11	-0.48 Units on a scale	Standard Error 0.19
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Work/school: Week 14	-0.65 Units on a scale	Standard Error 0.2
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Family life: Week 11	-0.54 Units on a scale	Standard Error 0.15
Placebo + ADT	Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol	Social life: Week 11	-0.68 Units on a scale	Standard Error 0.15

Comparison: Work/school: Week 11p-value: 0.034195% CI: [-1.01, -0.04]Mixed Models Analysis

Comparison: School/work: Week 14p-value: 0.081695% CI: [-0.99, 0.06]Mixed Models Analysis

Comparison: Work/school: Week 11p-value: 0.256195% CI: [-0.21, 0.78]Mixed Models Analysis

Comparison: Work/school: Week 14p-value: 0.295295% CI: [-0.82, 0.25]Mixed Models Analysis

Comparison: Social life: Week 11p-value: 0.033195% CI: [-0.82, -0.03]Mixed Models Analysis

Comparison: Social life: Week 14p-value: 0.035295% CI: [-0.9, -0.03]Mixed Models Analysis

Comparison: Social life: Week 11p-value: 0.48695% CI: [-0.54, 0.25]Mixed Models Analysis

Comparison: Social life: Week 14p-value: 0.028295% CI: [-0.93, -0.05]Mixed Models Analysis

Comparison: Family life: Week 11p-value: 0.001695% CI: [-1.01, -0.24]Mixed Models Analysis

Comparison: Family life: Week 14p-value: 0.018695% CI: [-0.94, -0.09]Mixed Models Analysis

Comparison: Family life: Week 11p-value: 0.082495% CI: [-0.73, 0.04]Mixed Models Analysis

Comparison: Family life: Week 14p-value: 0.007795% CI: [-1.02, -0.16]Mixed Models Analysis

Secondary

Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol

The efficacy of study medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. 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.

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 9	3.39 Units on a scale	Standard Deviation 0.65
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 10	3.1 Units on a scale	Standard Deviation 0.82
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 11	2.93 Units on a scale	Standard Deviation 0.8
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 12	2.8 Units on a scale	Standard Deviation 0.86
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 13	2.75 Units on a scale	Standard Deviation 0.86
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 14	2.71 Units on a scale	Standard Deviation 0.88
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 10	3.08 Units on a scale	Standard Deviation 0.84
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 12	2.81 Units on a scale	Standard Deviation 0.94
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 14	2.65 Units on a scale	Standard Deviation 1.09
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 9	3.42 Units on a scale	Standard Deviation 0.74
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 11	2.99 Units on a scale	Standard Deviation 0.89
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 13	2.72 Units on a scale	Standard Deviation 1
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 9	3.54 Units on a scale	Standard Deviation 0.65
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 13	3.01 Units on a scale	Standard Deviation 0.96
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 11	3.19 Units on a scale	Standard Deviation 0.86
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 14	2.9 Units on a scale	Standard Deviation 0.99
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 10	3.35 Units on a scale	Standard Deviation 0.84
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol	Week 12	3.06 Units on a scale	Standard Deviation 0.94

Comparison: Statistical analysis 1 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.027595% CI: [-0.26, -0.01]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.158395% CI: [-0.22, 0.04]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.002195% CI: [-0.41, -0.09]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.001895% CI: [-0.4, -0.09]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.001195% CI: [-0.43, -0.11]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.023595% CI: [-0.36, -0.03]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.002195% CI: [-0.44, -0.1]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.011195% CI: [-0.42, -0.05]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.00395% CI: [-0.44, -0.09]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.004695% CI: [-0.47, -0.09]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.023795% CI: [-0.39, -0.03]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.017195% CI: [-0.45, -0.04]Cochran-Mantel-Haenszel

Secondary

Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set

Time frame: Week 8 to Week 14

Arm	Measure	Group	Value (MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 9	3.36 Units on a scale	Standard Deviation 0.68
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 10	3.08 Units on a scale	Standard Deviation 0.85
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 11	2.91 Units on a scale	Standard Deviation 0.82
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 12	2.78 Units on a scale	Standard Deviation 0.87
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 13	2.72 Units on a scale	Standard Deviation 0.87
Brexpiprazole (1mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 14	2.69 Units on a scale	Standard Deviation 0.89
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 14	2.66 Units on a scale	Standard Deviation 1.1
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 9	3.4 Units on a scale	Standard Deviation 0.75
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 12	2.81 Units on a scale	Standard Deviation 0.95
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 13	2.73 Units on a scale	Standard Deviation 1.01
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 10	3.09 Units on a scale	Standard Deviation 0.85
Brexpiprazole (3mg) + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 11	2.99 Units on a scale	Standard Deviation 0.89
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 10	3.34 Units on a scale	Standard Deviation 0.85
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 11	3.17 Units on a scale	Standard Deviation 0.88
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 14	2.85 Units on a scale	Standard Deviation 1.01
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 12	3.02 Units on a scale	Standard Deviation 0.95
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 9	3.51 Units on a scale	Standard Deviation 0.67
Placebo + ADT	Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set	Week 13	2.97 Units on a scale	Standard Deviation 1

Comparison: Statistical analysis 1 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.024895% CI: [-0.26, -0.02]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.133495% CI: [-0.22, 0.03]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.000995% CI: [-0.42, -0.11]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.001995% CI: [-0.38, -0.09]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.000995% CI: [-0.42, -0.11]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.025495% CI: [-0.34, -0.02]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.003595% CI: [-0.41, -0.08]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.015295% CI: [-0.39, -0.04]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.00495% CI: [-0.42, -0.08]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.01395% CI: [-0.42, -0.05]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.075595% CI: [-0.33, 0.02]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The LOCF method was used to impute missing data.p-value: 0.052795% CI: [-0.39, 0]Cochran-Mantel-Haenszel

Secondary

Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol

The IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms as well as atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items were not included in the calculation of the total score. The IDSSR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDS-SR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 9	-3.27 Units on a scale	Standard Error 0.42
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 10	-4.7 Units on a scale	Standard Error 0.51
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 11	-5.77 Units on a scale	Standard Error 0.57
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 12	-6.33 Units on a scale	Standard Error 0.61
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 13	-6.88 Units on a scale	Standard Error 0.64
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 14	-6.97 Units on a scale	Standard Error 0.67
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 14	-7.2 Units on a scale	Standard Error 0.68
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 9	-2.65 Units on a scale	Standard Error 0.42
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 12	-6.05 Units on a scale	Standard Error 0.61
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 13	-6.97 Units on a scale	Standard Error 0.64
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 10	-4.13 Units on a scale	Standard Error 0.51
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 11	-4.29 Units on a scale	Standard Error 0.58
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 10	-2.94 Units on a scale	Standard Error 0.52
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 11	-3.46 Units on a scale	Standard Error 0.59
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 14	-5.07 Units on a scale	Standard Error 0.69
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 12	-4.18 Units on a scale	Standard Error 0.63
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 9	-2.15 Units on a scale	Standard Error 0.43
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol	Week 13	-5.25 Units on a scale	Standard Error 0.66

Comparison: Statistical analysis 1 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.049695% CI: [-2.24, 0]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.38795% CI: [-1.61, 0.63]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.012595% CI: [-3.13, -0.38]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.089895% CI: [-2.57, 0.19]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.00495% CI: [-3.88, -0.74]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.30195% CI: [-2.4, 0.74]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.011895% CI: [-3.82, -0.48]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.028795% CI: [-3.54, -0.19]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.068695% CI: [-3.39, 0.12]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.05695% CI: [-3.47, 0.04]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.044895% CI: [-3.75, -0.04]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.025195% CI: [-3.98, -0.27]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set

IDS-SR was a 30-item self-report measured to assess core diagnostic depressive symptoms and atypical and melancholic symptom features of major depressive disorders. The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items were not included in the calculation of the total score. The IDS-SR Total Score was the sum of ratings of 28 item scores. The possible IDSSR Total Score ranged from 0 to 84. The IDS-SR Total Score was un-evaluable if less than 23 of the 28 items were recorded. If the number of items recorded was at least 23 and at most 27, the IDS-SR Total Score was the mean of the recorded items multiplied by 28, and was then rounded off to the first decimal place.

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 9	-3.58 Units on a scale	Standard Error 0.41
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 10	-4.97 Units on a scale	Standard Error 0.49
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 11	-5.83 Units on a scale	Standard Error 0.56
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 12	-6.33 Units on a scale	Standard Error 0.59
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 14	-7.02 Units on a scale	Standard Error 0.66
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 13	-6.96 Units on a scale	Standard Error 0.63
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 13	-6.62 Units on a scale	Standard Error 0.63
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 9	-2.68 Units on a scale	Standard Error 0.42
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 14	-6.94 Units on a scale	Standard Error 0.66
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 12	-5.77 Units on a scale	Standard Error 0.59
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 10	-4.00 Units on a scale	Standard Error 0.5
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 11	-4.15 Units on a scale	Standard Error 0.56
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 10	-3.11 Units on a scale	Standard Error 0.5
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 11	-3.74 Units on a scale	Standard Error 0.57
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 12	-4.43 Units on a scale	Standard Error 0.6
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 9	-2.31 Units on a scale	Standard Error 0.42
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 13	-5.66 Units on a scale	Standard Error 0.64
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set	Week 14	-5.42 Units on a scale	Standard Error 0.67

Comparison: Statistical analysis 1 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.022895% CI: [-2.37, -0.18]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.508195% CI: [-1.47, 0.73]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.006495% CI: [-3.2, -0.53]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.189895% CI: [-2.23, 0.44]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.007495% CI: [-3.62, -0.56]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.593595% CI: [-1.95, 1.11]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.021195% CI: [-3.52, -0.29]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.103195% CI: [-2.96, 0.27]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.136695% CI: [-3.02, 0.41]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.270995% CI: [-2.68, 0.75]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.081295% CI: [-3.4, 0.2]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.100195% CI: [-3.33, 0.29]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol

Time frame: Week 8, 9, 10, 11, 12, and 13

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 9	-3.09 Units on a scale	Standard Error 0.31
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 13	-7.56 Units on a scale	Standard Error 0.47
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 11	-6.22 Units on a scale	Standard Error 0.42
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 12	-7.09 Units on a scale	Standard Error 0.45
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 10	-5.12 Units on a scale	Standard Error 0.39
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 13	-8.05 Units on a scale	Standard Error 0.48
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 11	-5.76 Units on a scale	Standard Error 0.43
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 12	-7.11 Units on a scale	Standard Error 0.45
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 9	-2.6 Units on a scale	Standard Error 0.31
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 10	-4.92 Units on a scale	Standard Error 0.39
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 10	-3.95 Units on a scale	Standard Error 0.4
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 9	-2.18 Units on a scale	Standard Error 0.32
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 11	-4.86 Units on a scale	Standard Error 0.43
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 13	-5.93 Units on a scale	Standard Error 0.49
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol	Week 12	-5.48 Units on a scale	Standard Error 0.46

Comparison: Statistical analysis 1 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.028695% CI: [-1.74, -0.1]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.317395% CI: [-1.24, 0.4]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.031395% CI: [-2.23, -0.11]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.073295% CI: [-2.04, 0.09]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.020695% CI: [-2.51, -0.21]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.123395% CI: [-2.06, 0.25]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.009795% CI: [-2.84, -0.39]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.009295% CI: [-2.86, -0.41]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.013995% CI: [-2.94, -0.33]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.001595% CI: [-3.42, -0.81]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set

Time frame: Week 8, 9, 10, 11, 12, and 13

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 12	-7.08 Units on a scale	Standard Error 0.43
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 11	-6.25 Units on a scale	Standard Error 0.41
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 9	-3.25 Units on a scale	Standard Error 0.3
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 10	-5.34 Units on a scale	Standard Error 0.38
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 13	-7.55 Units on a scale	Standard Error 0.46
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 11	-5.56 Units on a scale	Standard Error 0.41
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 9	-2.53 Units on a scale	Standard Error 0.3
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 10	-4.8 Units on a scale	Standard Error 0.38
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 12	-6.8 Units on a scale	Standard Error 0.44
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 13	-7.73 Units on a scale	Standard Error 0.46
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 13	-6.04 Units on a scale	Standard Error 0.47
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 12	-5.52 Units on a scale	Standard Error 0.44
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 9	-2.19 Units on a scale	Standard Error 0.31
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 11	-4.85 Units on a scale	Standard Error 0.41
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set	Week 10	-3.91 Units on a scale	Standard Error 0.39

Comparison: Statistical analysis at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.009695% CI: [-1.86, -0.26]Mixed Models Analysis

Comparison: Statistical analysis at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.006595% CI: [-2.47, -0.4]Mixed Models Analysis

Comparison: Statistical analysis at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.013995% CI: [-2.5, -0.28]Mixed Models Analysis

Comparison: Statistical analysis at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.009995% CI: [-2.75, -0.38]Mixed Models Analysis

Comparison: Statistical analysis at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.017795% CI: [-2.8, -0.27]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set

The HAM-D17 was utilized as a secondary assessment of a participants level of depression. The HAM-D (17-Item) consisted of 17 items. Eight items were rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) were rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 was the best rating and the highest score (2 or 4) was the worst rating. The possible total scores were from 0 to 52, with higher scores indicating more severe depression.

Time frame: Baseline and Week 14

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set	-5.47 Units on a scale	Standard Error 0.36
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set	-6.14 Units on a scale	Standard Error 0.36
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set	-4.8 Units on a scale	Standard Error 0.37

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The last observation carried forward (LOCF) method was used to impute missing data.p-value: 0.173295% CI: [-1.63, 0.29]ANCOVA

Comparison: Statistical analysis 2 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B. The last observation carried forward (LOCF) method was used to impute missing data.p-value: 0.006695% CI: [-2.31, -0.37]ANCOVA

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol

The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the best rating and 4 is the worst rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher score indicating worse anxiety symptoms.

Time frame: Baseline and Week 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol	-3.35 Units on a scale	Standard Error 0.32
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol	-3.96 Units on a scale	Standard Error 0.33
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol	-3.07 Units on a scale	Standard Error 0.33

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol

Time frame: Baseline and Week 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol	-5.36 Units on a scale	Standard Error 0.37
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol	-6.26 Units on a scale	Standard Error 0.38
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol	-4.57 Units on a scale	Standard Error 0.39

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set

Time frame: Baseline and Week 14

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set	-3.43 Units on a scale	Standard Error 0.31
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set	-3.89 Units on a scale	Standard Error 0.31
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set	-3.33 Units on a scale	Standard Error 0.32

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol

The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. 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. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.

Time frame: Week 11 and Week 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 11	-1.11 Units on a scale	Standard Error 0.13
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 14	-1.27 Units on a scale	Standard Error 0.15
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 11	-0.74 Units on a scale	Standard Error 0.13
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 14	-1.26 Units on a scale	Standard Error 0.15
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 11	-0.53 Units on a scale	Standard Error 0.14
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol	Week 14	-0.78 Units on a scale	Standard Error 0.15

Comparison: Statistical analysis 1 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.001595% CI: [-0.94, -0.22]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.262795% CI: [-0.56, 0.15]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3p-value: 0.015895% CI: [-0.89, -0.09]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.019195% CI: [-0.88, -0.08]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set

The SDS was a self-rated instrument used to measure the effect of the participants symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores ranged from 0 through 10. 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. For the work/school item, no response was to be entered if the participant did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS score were calculated over the three item scores. All three item scores were needed to be available with the exception of the work/school item score when this item was not applicable.

Time frame: Week 11 and Week 14

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 11	-1.13 Units on a scale	Standard Error 0.13
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 14	-1.33 Units on a scale	Standard Error 0.14
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 11	-0.67 Units on a scale	Standard Error 0.13
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 14	-1.21 Units on a scale	Standard Error 0.13
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 11	-0.58 Units on a scale	Standard Error 0.11
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set	Week 14	-0.84 Units on a scale	Standard Error 0.13

Comparison: Statistical analysis 1 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.000895% CI: [-0.87, -0.23]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase Bp-value: 0.579295% CI: [-0.41, 0.23]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.009195% CI: [-0.87, -0.12]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.047495% CI: [-0.73, 0]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol

The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the study physician had to answer 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.

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 14	-0.87 Units on a scale	Standard Error 0.06
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 11	-0.64 Units on a scale	Standard Error 0.05
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 13	-0.77 Units on a scale	Standard Error 0.06
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 9	-0.24 Units on a scale	Standard Error 0.03
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 12	-0.73 Units on a scale	Standard Error 0.06
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 10	-0.5 Units on a scale	Standard Error 0.05
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 12	-0.74 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 13	-0.8 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 10	-0.47 Units on a scale	Standard Error 0.05
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 14	-0.92 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 9	-0.23 Units on a scale	Standard Error 0.03
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 11	-0.53 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 11	-0.45 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 9	-0.16 Units on a scale	Standard Error 0.03
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 10	-0.33 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 14	-0.72 Units on a scale	Standard Error 0.06
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 12	-0.58 Units on a scale	Standard Error 0.06
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol	Week 13	-0.64 Units on a scale	Standard Error 0.06

Comparison: Statistical analysis 1 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.081795% CI: [-0.17, 0.01]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 9. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.140695% CI: [-0.16, 0.02]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.01195% CI: [-0.29, -0.04]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 10. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.028795% CI: [-0.27, -0.02]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.007195% CI: [-0.32, -0.05]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.250395% CI: [-0.22, -0.06]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.053995% CI: [-0.3, 0]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 12. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.039895% CI: [-0.31, -0.01]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.116895% CI: [-0.3, 0.03]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 13. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.062195% CI: [-0.32, 0.01]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.08995% CI: [-0.32, 0.02]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 14. All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.p-value: 0.021395% CI: [-0.38, -0.03]Mixed Models Analysis

Secondary

Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set

Time frame: Weeks 8, 9, 10, 11, 12,13 and 14

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 10	-0.52 Units on a scale	Standard Error 0.05
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 9	-0.25 Units on a scale	Standard Error 0.03
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 11	-0.64 Units on a scale	Standard Error 0.05
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 12	-0.73 Units on a scale	Standard Error 0.05
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 13	-0.78 Units on a scale	Standard Error 0.06
Brexpiprazole (1mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 14	-0.86 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 9	-0.22 Units on a scale	Standard Error 0.03
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 10	-0.46 Units on a scale	Standard Error 0.05
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 11	-0.51 Units on a scale	Standard Error 0.05
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 13	-0.77 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 14	-0.9 Units on a scale	Standard Error 0.06
Brexpiprazole (3mg) + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 12	-0.72 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 9	-0.16 Units on a scale	Standard Error 0.03
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 12	-0.59 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 10	-0.31 Units on a scale	Standard Error 0.05
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 14	-0.75 Units on a scale	Standard Error 0.06
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 13	-0.66 Units on a scale	Standard Error 0.06
Placebo + ADT	Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set	Week 11	-0.44 Units on a scale	Standard Error 0.05

Comparison: Statistical analysis 1 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.043695% CI: [-0.18, 0]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 9. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: -0.0695% CI: [-0.15, 0.03]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.001295% CI: [-0.34, -0.08]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 10. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.026695% CI: [-0.27, -0.02]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.003495% CI: [-0.33, -0.07]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 11. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.305395% CI: [-0.2, 0.06]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.054195% CI: [-0.29, 0]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 12. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.091295% CI: [-0.28, 0.02]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.155395% CI: [-0.28, 0.04]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 13. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.185595% CI: [-0.27, 0.05]Mixed Models Analysis

Comparison: Statistical analysis 1 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.201595% CI: [-0.28, 0.06]Mixed Models Analysis

Comparison: Statistical analysis 2 at Week 14. The Efficacy Sample Set included all participants who had received at least one dose of study treatment and had both an end of Phase A (Week 8) value and at least 1 post randomization efficacy evaluation for MADRS Total Score in Phase B.p-value: 0.085295% CI: [-0.32, 0.02]Mixed Models Analysis

Secondary

Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol

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

Time frame: Weeks, 8, 9, 10, 11, 12, 13, and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	7.69 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	21.8 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	27.5 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	34.1 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	38.9 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	41.2 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	48.4 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	9.52 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	38 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	44.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	23 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	30 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	12.3 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	19.7 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	34 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	27.6 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	5.53 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	27.1 Percentage of participants

Secondary

Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set

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

Time frame: Weeks 8, 9, 10, 11, 12, 13 and 14

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	9.46 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	23.6 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	28.4 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	35.1 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	40 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	41.8 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	47.8 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	10.4 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	38.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	43.4 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	23 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	30.1 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	13.3 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	21.6 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	36.7 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	29.4 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	6.54 Percentage of participants
Placebo + ADT	Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	28.9 Percentage of participants

Secondary

Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol

MADRS remission was defined as a \< or equal to 10 and \> or equal to 50% reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.

Time frame: Weeks 8, 9, 10, 11, 12, 13 and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 9	1.92 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 10	2.37 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 11	8.06 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 12	10.4 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 13	9.95 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 14	14.7 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 14	14.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 9	0.48 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 12	9.39 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 13	13.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 10	2.82 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 11	6.57 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 10	3.94 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 11	5.42 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 14	10.8 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 12	6.4 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 9	3.02 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol	Week 13	8.37 Percentage of participants

Comparison: Statistical analysis 1 at Week 11 All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.302795% CI: [0.7, 3.1]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 2 at Week 11 All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.69695% CI: [0.54, 2.52]Cochran-Mantel-Haenszel

Comparison: Statistical analysis 1 at Week 12 All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3. The LOCF method was used to impute missing data.p-value: 0.136895% CI: [0.86, 3.07]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set

Time frame: Weeks 8, 9, 10, 11, 12, 13 and 14

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 9	3.15 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 10	4 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 11	8.44 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 12	11.1 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 13	10.7 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 14	15.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 14	13.7 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 9	0.45 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 12	8.85 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 13	12.8 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 10	2.65 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 11	6.19 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 10	4.13 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 11	5.5 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 14	11.9 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 12	5.96 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 9	2.8 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set	Week 13	9.17 Percentage of participants

Secondary

Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol

MADRS response was defined as \>=50 percent reduction in MADRS Total Score from end of Phase A (Week 8). The MADRS was utilized as an efficacy assessment of a participant's level of depression. The MADRS consisted 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 were to be unevaluable if less than 8 of the 10 items were recorded. If 8 or 9 of the 10 items were recorded, the MADRS total score was the mean of the recorded items multiplied by 10 and then rounded of to the first decimal place. 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.

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	3.37 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	7.58 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	13.3 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	16.6 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	18 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	23.2 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	23 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	0.48 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	16.4 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	19.2 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	6.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	11.3 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 10	4.93 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 11	8.37 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 14	14.3 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 12	10.3 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 9	3.02 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol	Week 13	14.3 Percentage of participants

Secondary

Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set

Time frame: Weeks 8, 9, 10, 11, 12, 13, and 14

Arm	Measure	Group	Value (NUMBER)
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	4.5 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	10.2 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	13.3 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	16.9 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	18.2 Percentage of participants
Brexpiprazole (1mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	23.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	22.1 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	0.45 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	15.5 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	18.6 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	6.19 Percentage of participants
Brexpiprazole (3mg) + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	10.6 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 10	5.05 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 11	8.72 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 14	15.1 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 12	10.1 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 9	2.8 Percentage of participants
Placebo + ADT	Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set	Week 13	15.6 Percentage of participants

Source: ClinicalTrials.gov · Data processed: Mar 13, 2026

Study of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Polaris Trial)

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Brief summary

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Exclusion criteria

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Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Mean Change From the End of Phase A (Week 8 Visit) to Phase B (Week 14 Visit) in the Montgomery-Asberg Depression Rating Scale for the Efficacy Sample Set

Mean Change in MADRS Total Score From Baseline End of Week 8 to Week 14 for the Efficacy Sample Per Final Protocol

Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set

Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Set Per Final Protocol

Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Per Final Protocol

Mean CGI-I Score at Each Trial Week Visit in Phase B for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in IDS-SR Total Score for the Efficacy Sample Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) for Every Study Week Visit in Phase B in Inventory of Depressive Symptomatology (Self-Report) IDS-SR Total Score for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) in MADRS Total Score for Every Study Week Visit in Phase B Other Than Week 14 Visit for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) Hamilton Depression Scale 17 Item Version (HAM)-D17 Total Score for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-A Total for the Efficacy Sample Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in HAM-D17 Total Score for the Efficacy Sample Set Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Hamilton Anxiety Rating Scale (HAM-A) Total Score for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in SDS Mean Scores for the Efficacy Sample Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) to End of Phase B (Week 14 Visit) in Sheehan Disability Scale (SDS) Mean Scores for the Efficacy Sample Set

Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical CGI-S for the Efficacy Sample Per Final Protocol

Mean Change From End of Phase A (Week 8 Visit) to Phase B by Study Week in Clinical Global Impression Severity of Illness (CGI-S) for the Efficacy Sample Set

Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol

Percentage of Participants With a CGI-I Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set

Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Per Final Protocol

Percentage of Participants With a MADRS Remission During Phase B Relative to the End of Phase A (Week 8) for the Efficacy Sample Set

Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Per Final Protocol

Percentage of Participants With a MADRS Response During Phase B Relative to the End of Phase A (Week 8 Visit) for the Efficacy Sample Set