Trial Outcomes & Findings for Study of the Safety and Efficacy of Fixed Dose OPC-34712 as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder (the Pyxis Trial) (NCT NCT01360645)

NCT ID: NCT01360645

Last Updated: 2015-11-26

Results Overview

The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 826 participants
• Primary outcome timeframe: Baseline and Week 14
• Results posted on: 2015-11-26

Participant Flow

This trial was conducted in 826 subjects at 59 trial sites in the following 5 countries: United States, Canada, Poland, Slovakia, and France.

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.

Participant milestones

Measure	Single-blind Placebo + ADT In Phase A, participants were administered placebo as an adjunctive therapy to an open label ADT for 8 weeks	Brexpiprazole 2 mg/Day + ADT Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Phase A+ Placebo + ADT Participants who did not meet criteria for randomization and a follow-up of 30 (+2) days after the last dose of study medication were in Phase A+
Placebo+ADT Prospective Phase-A(8 Weeks) STARTED	824	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) COMPLETED	710	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) NOT COMPLETED	114	0	0	0
Phase B (6 Weeks) STARTED	0	188	191	0
Phase B (6 Weeks) COMPLETED	0	174	178	0
Phase B (6 Weeks) NOT COMPLETED	0	14	13	0
Phase A+ STARTED	0	0	0	331
Phase A+ COMPLETED	0	0	0	307
Phase A+ NOT COMPLETED	0	0	0	24

Reasons for withdrawal

Measure	Single-blind Placebo + ADT In Phase A, participants were administered placebo as an adjunctive therapy to an open label ADT for 8 weeks	Brexpiprazole 2 mg/Day + ADT Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Phase A+ Placebo + ADT Participants who did not meet criteria for randomization and a follow-up of 30 (+2) days after the last dose of study medication were in Phase A+
Placebo+ADT Prospective Phase-A(8 Weeks) Lost to Follow-up	16	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) Adverse Event	19	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) Met Withdrawal Criteria	16	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) Withdrawal by Subject	34	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) Protocol Deviation	24	0	0	0
Placebo+ADT Prospective Phase-A(8 Weeks) Physician Decision	5	0	0	0
Phase B (6 Weeks) Lost to Follow-up	0	1	0	0
Phase B (6 Weeks) Adverse Event	0	6	0	0
Phase B (6 Weeks) Met Withdrawal Criteria	0	3	2	0
Phase B (6 Weeks) Withdrawal by Subject	0	3	8	0
Phase B (6 Weeks) Protocol Deviation	0	1	3	0
Phase A+ Lost to Follow-up	0	0	0	7
Phase A+ Adverse Event	0	0	0	2
Phase A+ Met Withdrawal Criteria	0	0	0	4
Phase A+ Physician Decision	0	0	0	2
Phase A+ Withdrawal by Subject	0	0	0	5
Phase A+ Protocol Deviation	0	0	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Brexpiprazole 2 mg/Day + ADT n=188 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Total n=379 Participants Total of all reporting groups
Age, Continuous	44.1 Years STANDARD_DEVIATION 11.6 • n=93 Participants	45.2 Years STANDARD_DEVIATION 11.3 • n=4 Participants	44.6 Years STANDARD_DEVIATION 11.5 • n=27 Participants
Sex: Female, Male Female	130 Participants n=93 Participants	137 Participants n=4 Participants	267 Participants n=27 Participants
Sex: Female, Male Male	58 Participants n=93 Participants	54 Participants n=4 Participants	112 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample.	-8.27 Units on a scale Standard Error 0.61	-5.15 Units on a scale Standard Error 0.60

PRIMARY outcome

Timeframe: 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.

The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol.	-8.36 Units on a scale Standard Error 0.64	-5.15 Units on a scale Standard Error 0.63

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=179 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=181 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample.	-1.35 Units on a scale Standard Error 0.17	-0.91 Units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=167 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=170 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol	-1.35 Units on a scale Standard Error 0.17	-0.89 Units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Week 9, 10, 11, 12, and 13

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. Week 10	-5.15 Units on a scale Standard Error 0.47	-3.43 Units on a scale Standard Error 0.47
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. Week 9	-3.15 Units on a scale Standard Error 0.40	-1.86 Units on a scale Standard Error 0.39
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. Week 11	-6.69 Units on a scale Standard Error 0.52	-4.06 Units on a scale Standard Error 0.52
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. Week 12	-7.22 Units on a scale Standard Error 0.55	-4.63 Units on a scale Standard Error 0.54
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. Week 13	-8.28 Units on a scale Standard Error 0.58	-5.10 Units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Week 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.

The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the "best" rating and 6 being the "worst" rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. Week 11	-6.58 Units on a scale Standard Error 0.54	-4.17 Units on a scale Standard Error 0.53
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. Week 13	-8.28 Units on a scale Standard Error 0.61	-5.01 Units on a scale Standard Error 0.60
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. Week 9	-3.05 Units on a scale Standard Error 0.41	-1.74 Units on a scale Standard Error 0.41
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. Week 10	-5.04 Units on a scale Standard Error 0.49	-3.52 Units on a scale Standard Error 0.48
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. Week 12	-7.24 Units on a scale Standard Error 0.58	-4.72 Units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Week 9, 10, 11, 12, 13, and 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 13	2.74 Units on a scale Standard Deviation 1.07	3.13 Units on a scale Standard Deviation 1.06
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 9	3.41 Units on a scale Standard Deviation 0.83	3.62 Units on a scale Standard Deviation 0.74
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 10	3.17 Units on a scale Standard Deviation 0.89	3.37 Units on a scale Standard Deviation 0.82
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 11	3.03 Units on a scale Standard Deviation 1.02	3.23 Units on a scale Standard Deviation 0.90
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 12	2.84 Units on a scale Standard Deviation 0.99	3.19 Units on a scale Standard Deviation 1.04
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. Week 14	2.75 Units on a scale Standard Deviation 1.13	3.13 Units on a scale Standard Deviation 1.09

SECONDARY outcome

Timeframe: Week 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. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 13	2.78 Units on a scale Standard Deviation 1.07	3.18 Units on a scale Standard Deviation 1.06
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 9	3.44 Units on a scale Standard Deviation 0.81	3.67 Units on a scale Standard Deviation 0.70
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 10	3.21 Units on a scale Standard Deviation 0.89	3.40 Units on a scale Standard Deviation 0.82
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 11	3.07 Units on a scale Standard Deviation 1.01	3.25 Units on a scale Standard Deviation 0.89
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 12	2.85 Units on a scale Standard Deviation 1.01	3.23 Units on a scale Standard Deviation 1.05
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. Week 14	2.77 Units on a scale Standard Deviation 1.14	3.17 Units on a scale Standard Deviation 1.10

SECONDARY outcome

Timeframe: Week 9, 10, 11, 12, 13, and 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

Items on CGI-S scale are: 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, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 11	-0.61 Units on a scale Standard Error 0.06	-0.40 Units on a scale Standard Error 0.06
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 9	-0.25 Units on a scale Standard Error 0.05	-0.12 Units on a scale Standard Error 0.05
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 12	-0.70 Units on a scale Standard Error 0.07	-0.45 Units on a scale Standard Error 0.06
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 10	-0.45 Units on a scale Standard Error 0.05	-0.31 Units on a scale Standard Error 0.05
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 13	-0.86 Units on a scale Standard Error 0.07	-0.50 Units on a scale Standard Error 0.07
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. Week 14	-0.91 Units on a scale Standard Error 0.07	-0.58 Units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 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.

Items on CGI-S scale are: 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, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 9	-0.24 Units on a scale Standard Error 0.05	-0.09 Units on a scale Standard Error 0.05
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 10	-0.43 Units on a scale Standard Error 0.06	-0.32 Units on a scale Standard Error 0.06
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 11	-0.58 Units on a scale Standard Error 0.06	-0.42 Units on a scale Standard Error 0.06
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 12	-0.70 Units on a scale Standard Error 0.07	-0.46 Units on a scale Standard Error 0.07
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 13	-0.85 Units on a scale Standard Error 0.07	-0.50 Units on a scale Standard Error 0.07
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. Week 14	-0.91 Units on a scale Standard Error 0.07	-0.57 Units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Week 9, 10, 11, 12, 13, and 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

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 are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14.

The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 9	-3.02 Units on a scale Standard Error 0.52	-1.45 Units on a scale Standard Error 0.51
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 10	-4.17 Units on a scale Standard Error 0.59	-2.64 Units on a scale Standard Error 0.59
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 11	-5.41 Units on a scale Standard Error 0.65	-4.31 Units on a scale Standard Error 0.64
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 12	-6.16 Units on a scale Standard Error 0.68	-4.69 Units on a scale Standard Error 0.67
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 13	-7.00 Units on a scale Standard Error 0.72	-5.25 Units on a scale Standard Error 0.71
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. Week 14	-7.49 Units on a scale Standard Error 0.74	-5.52 Units on a scale Standard Error 0.73

SECONDARY outcome

Timeframe: Week 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.

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 are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14.

The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 9	-3.30 Units on a scale Standard Error 0.53	-1.59 Units on a scale Standard Error 0.51
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 10	-4.29 Units on a scale Standard Error 0.61	-3.13 Units on a scale Standard Error 0.60
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 11	-5.45 Units on a scale Standard Error 0.67	-4.73 Units on a scale Standard Error 0.66
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 12	-6.32 Units on a scale Standard Error 0.71	-5.06 Units on a scale Standard Error 0.70
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 13	-7.03 Units on a scale Standard Error 0.74	-5.60 Units on a scale Standard Error 0.73
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. Week 14	-7.59 Units on a scale Standard Error 0.77	-6.05 Units on a scale Standard Error 0.75

SECONDARY outcome

Timeframe: Week 11 and 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Work/School: Week 11	-0.70 Units on a scale Standard Error 0.21	-0.42 Units on a scale Standard Error 0.22
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Work/School: Week 14	-1.09 Units on a scale Standard Error 0.22	-0.90 Units on a scale Standard Error 0.22
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Social life: Week 11	-1.17 Units on a scale Standard Error 0.17	-0.67 Units on a scale Standard Error 0.17
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Social life: Week 14	-1.54 Units on a scale Standard Error 0.19	-1.04 Units on a scale Standard Error 0.18
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Family life: Week 11	-1.06 Units on a scale Standard Error 0.18	-0.43 Units on a scale Standard Error 0.18
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. Item: Family life: Week 14	-1.33 Units on a scale Standard Error 0.19	-0.73 Units on a scale Standard Error 0.19

SECONDARY outcome

Timeframe: Week 11 and 14

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

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Work/School: Week 11	-0.76 Units on a scale Standard Error 0.22	-0.58 Units on a scale Standard Error 0.22
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Work/School: Week 14	-1.11 Units on a scale Standard Error 0.23	-0.96 Units on a scale Standard Error 0.23
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Family life: Week 14	-0.43 Units on a scale Standard Error 0.18	-0.70 Units on a scale Standard Error 0.19
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Social life: Week 11	-1.18 Units on a scale Standard Error 0.18	-0.69 Units on a scale Standard Error 0.18
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Social life: Week 14	-1.57 Units on a scale Standard Error 0.19	-1.02 Units on a scale Standard Error 0.19
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. Item: Family life: Week 11	-0.99 Units on a scale Standard Error 0.19	-0.43 Units on a scale Standard Error 0.18

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: Efficacy Sample comprised all participants in Safety Sample who had end of Phase A value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The Last-observation-carried-forward (LOCF) data set included data recorded at Phase B visit, if no observation was recorded, data was carried forward from previous visit.

The HAM-D (17-Item) consists of 17 items. Eight items are 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) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the "best" rating and the highest score (2 or 4) is the "worst" rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=183 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=188 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample.	-5.89 Units on a scale Standard Error 0.48	-3.55 Units on a scale Standard Error 0.47

SECONDARY outcome

Timeframe: 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. The LOCF data set included data recorded at Phase B visit, if no observation was recorded, data was carried forward from previous visit.

The HAM-D (17-Item) consists of 17 items. Eight items are 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) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the "best" rating and the highest score (2 or 4) is the "worst" rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=172 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=175 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.	-5.89 Units on a scale Standard Error 0.51	-3.59 Units on a scale Standard Error 0.49

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=181 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=188 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample	-3.94 Units on a scale Standard Error 0.43	-2.77 Units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: 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. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

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.

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=171 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=175 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.	-3.79 Units on a scale Standard Error 0.45	-2.70 Units on a scale Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

The MADRS response was defined as >/=50% reduction in MADRS total score from end of Phase A (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	23.5 Percentage of participants	14.7 Percentage of participants

SECONDARY outcome

Timeframe: 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. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

The MADRS response was defined as >/=50% reduction in MADRS total score from end of Phase A (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	23.4 Percentage of participants	15.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

MADRS remission was defined as </=10 and >/=50% reduction in MADRS total score from end of Phase A (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	14.4 Percentage of participants	8.38 Percentage of participants

SECONDARY outcome

Timeframe: 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. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

MADRS remission was defined as </=10 and >/=50% reduction in MADRS total score from end of Phase A (Week 8).

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	14.9 Percentage of participants	8.99 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 14

Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

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

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=187 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.	44.4 Percentage of participants	27.7 Percentage of participants

SECONDARY outcome

Timeframe: 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. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.

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

Outcome measures

Measure	Brexpiprazole 2 mg/Day + ADT n=175 Participants Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=178 Participants Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.	43.4 Percentage of participants	26.4 Percentage of participants

Adverse Events

Brexpiprazole 2 mg/Day + ADT

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Double-blind Placebo + ADT

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Brexpiprazole 2 mg/Day + ADT n=188 participants at risk Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 participants at risk Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Cardiac disorders Atrial Fibrillation	0.00% 0/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	0.52% 1/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Gastrointestinal disorders Abdominal Pain	0.53% 1/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	0.00% 0/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Infections and infestations Pneumonia	0.00% 0/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	0.52% 1/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Injury, poisoning and procedural complications Comminuted Fracture	0.53% 1/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	0.00% 0/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Nervous system disorders Syncope	0.53% 1/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	0.00% 0/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.

Other adverse events

Measure	Brexpiprazole 2 mg/Day + ADT n=188 participants at risk Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.	Double-blind Placebo + ADT n=191 participants at risk Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit.
Gastrointestinal disorders Diarrhoea	2.7% 5/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	5.2% 10/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Infections and infestations Upper resporatory tract infection	3.2% 6/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	6.3% 12/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Investigations Weight increased	8.0% 15/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	3.1% 6/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.
Nervous system disorders Akathisia	7.4% 14/188 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.	1.0% 2/191 • Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included. Safety sample comprised of randomized participants in Phase B who received at least one dose of double-blind trial medication. Participants were excluded only if there was evidence that the participant did not take trial medication. If a participant was dispensed trial medication and is lost to follow-up that participant was considered exposed.

Additional Information

Global Medical Affairs

Otsuka Pharmaceutical Development & Commercialization, Inc

Phone: 800 562-3974

Results disclosure agreements

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