Trial Outcomes & Findings for 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) (NCT NCT01360632)

NCT ID: NCT01360632

Last Updated: 2016-01-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1539 participants

Primary outcome timeframe

Baseline and Week 14

Results posted on

2016-01-01

Participant Flow

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

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

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 (1mg) + ADT
Participants were administered brexpiprazole of \[1mg (milligram)\] as an adjunctive therapy to an assigned open-label ADT (anti-depressant therapy).
Brexpiprazole (3mg) + ADT
Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.
Double-blind Placebo + ADT
In phase B, participants were administered placebo as an adjunctive therapy to an open label ADT for 6 weeks.
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+
Phase A (8 Weeks)
STARTED
1532
0
0
0
0
Phase A (8 Weeks)
COMPLETED
1277
0
0
0
0
Phase A (8 Weeks)
NOT COMPLETED
255
0
0
0
0
Phase B (6 Weeks)
STARTED
0
226
230
221
0
Phase B (6 Weeks)
COMPLETED
0
216
210
208
0
Phase B (6 Weeks)
NOT COMPLETED
0
10
20
13
0
Phase A+
STARTED
0
0
0
0
600
Phase A+
COMPLETED
0
0
0
0
575
Phase A+
NOT COMPLETED
0
0
0
0
25

Reasons for withdrawal

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 (1mg) + ADT
Participants were administered brexpiprazole of \[1mg (milligram)\] as an adjunctive therapy to an assigned open-label ADT (anti-depressant therapy).
Brexpiprazole (3mg) + ADT
Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.
Double-blind Placebo + ADT
In phase B, participants were administered placebo as an adjunctive therapy to an open label ADT for 6 weeks.
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+
Phase A (8 Weeks)
Lost to Follow-up
27
0
0
0
0
Phase A (8 Weeks)
Adverse Event
60
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)
Withdrawal by Subject
74
0
0
0
0
Phase A (8 Weeks)
Protocol Deviation
39
0
0
0
0
Phase B (6 Weeks)
Lost to Follow-up
0
1
1
0
0
Phase B (6 Weeks)
Adverse Event
0
3
9
3
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)
Withdrawal by Subject
0
4
4
7
0
Phase B (6 Weeks)
Protocol Deviation
0
1
4
1
0
Phase B (6 Weeks)
Lack of Efficacy
0
1
0
0
0
Phase A+
Lost to Follow-up
0
0
0
0
2
Phase A+
Adverse Event
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+
Withdrawal by Subject
0
0
0
0
8
Phase A+
Protocol Deviation
0
0
0
0
3

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Brexpiprazole (1mg + ADT)
n=226 Participants
Participants were administered brexpiprazole of 1mg as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (3mg + ADT)
n=230 Participants
Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=221 Participants
Participants were administered placebo as an adjunctive therapy to an open label ADT.
Total
n=677 Participants
Total of all reporting groups
Age, Continuous
45.7 Years
STANDARD_DEVIATION 11.6 • n=5 Participants
44.5 Years
STANDARD_DEVIATION 11.2 • n=7 Participants
46.6 Years
STANDARD_DEVIATION 11.0 • n=5 Participants
45.6 Years
STANDARD_DEVIATION 11.3 • n=4 Participants
Sex: Female, Male
Female
158 Participants
n=5 Participants
156 Participants
n=7 Participants
146 Participants
n=5 Participants
460 Participants
n=4 Participants
Sex: Female, Male
Male
68 Participants
n=5 Participants
74 Participants
n=7 Participants
75 Participants
n=5 Participants
217 Participants
n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-7.65 Units on a scale
Standard Error 0.5
-6.45 Units on a scale
Standard Error 0.51

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-7.64 Units on a scale
Standard Error 0.52
6.33 Units on a scale
Standard Error 0.53

SECONDARY outcome

Timeframe: Week 8, 9, 10, 11, 12, and 13

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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.25 Units on a scale
Standard Error 0.3
-2.19 Units on a scale
Standard Error 0.31
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
-5.34 Units on a scale
Standard Error 0.38
-3.91 Units on a scale
Standard Error 0.39
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
-6.25 Units on a scale
Standard Error 0.41
-4.85 Units on a scale
Standard Error 0.41
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
-7.08 Units on a scale
Standard Error 0.43
-5.52 Units on a scale
Standard Error 0.44
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
-7.55 Units on a scale
Standard Error 0.46
-6.04 Units on a scale
Standard Error 0.47

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.09 Units on a scale
Standard Error 0.31
-2.18 Units on a scale
Standard Error 0.32
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
-5.12 Units on a scale
Standard Error 0.39
-3.95 Units on a scale
Standard Error 0.4
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
-6.22 Units on a scale
Standard Error 0.42
-4.86 Units on a scale
Standard Error 0.43
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
-7.09 Units on a scale
Standard Error 0.45
-5.48 Units on a scale
Standard Error 0.46
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
-7.56 Units on a scale
Standard Error 0.47
-5.93 Units on a scale
Standard Error 0.49

SECONDARY outcome

Timeframe: Week 11 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-1.13 Units on a scale
Standard Error 0.13
-0.58 Units on a scale
Standard Error 0.11
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
-1.33 Units on a scale
Standard Error 0.14
-0.84 Units on a scale
Standard Error 0.13

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-1.11 Units on a scale
Standard Error 0.13
-0.53 Units on a scale
Standard Error 0.14
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
-1.27 Units on a scale
Standard Error 0.15
-0.78 Units on a scale
Standard Error 0.15

SECONDARY outcome

Timeframe: Week 11 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.

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

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-1.00 Units on a scale
Standard Error 0.16
-0.55 Units on a scale
Standard Error 0.15
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
-1.16 Units on a scale
Standard Error 0.17
-0.73 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 Set
Social life: Week 11
-0.76 Units on a scale
Standard Error 0.14
-1.13 Units on a scale
Standard Error 0.14
-0.72 Units on a scale
Standard Error 0.14
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
-1.39 Units on a scale
Standard Error 0.15
-0.91 Units on a scale
Standard Error 0.15
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
-1.14 Units on a scale
Standard Error 0.14
-0.51 Units on a scale
Standard Error 0.12
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
-1.35 Units on a scale
Standard Error 0.15
-0.80 Units on a scale
Standard Error 0.15

SECONDARY outcome

Timeframe: 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.

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

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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 0.20
-1.01 Units on a scale
Standard Error 0.18
-0.48 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 Set Per Final Protocol
Work/school: Week 14
-0.93 Units on a scale
Standard Error 0.21
-1.11 Units on a scale
Standard Error 0.20
-0.65 Units on a scale
Standard Error 0.20
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
-1.11 Units on a scale
Standard Error 0.15
-0.68 Units on a scale
Standard Error 0.15
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
-1.34 Units on a scale
Standard Error 0.16
-0.88 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 Set Per Final Protocol
Family life: Week 11
-0.89 Units on a scale
Standard Error 0.15
-1.17 Units on a scale
Standard Error 0.14
-0.54 Units on a scale
Standard Error 0.15
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
-1.32 Units on a scale
Standard Error 0.16
-0.81 Units on a scale
Standard Error 0.16

SECONDARY outcome

Timeframe: Weeks 8, 9, 10, 11, 12,13 and 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-0.25 Units on a scale
Standard Error 0.03
-0.16 Units on a scale
Standard Error 0.03
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
-0.52 Units on a scale
Standard Error 0.05
-0.31 Units on a scale
Standard Error 0.05
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
-0.64 Units on a scale
Standard Error 0.05
-0.44 Units on a scale
Standard Error 0.05
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
-0.73 Units on a scale
Standard Error 0.05
-0.59 Units on a scale
Standard Error 0.05
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
-0.78 Units on a scale
Standard Error 0.06
-0.66 Units on a scale
Standard Error 0.06
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
-0.86 Units on a scale
Standard Error 0.06
-0.75 Units on a scale
Standard Error 0.06

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-0.24 Units on a scale
Standard Error 0.03
-0.16 Units on a scale
Standard Error 0.03
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
-0.5 Units on a scale
Standard Error 0.05
-0.33 Units on a scale
Standard Error 0.05
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
-0.64 Units on a scale
Standard Error 0.05
-0.45 Units on a scale
Standard Error 0.05
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
-0.73 Units on a scale
Standard Error 0.06
-0.58 Units on a scale
Standard Error 0.06
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
-0.77 Units on a scale
Standard Error 0.06
-0.64 Units on a scale
Standard Error 0.06
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
-0.87 Units on a scale
Standard Error 0.06
-0.72 Units on a scale
Standard Error 0.06

SECONDARY outcome

Timeframe: Weeks 8, 9, 10, 11, 12, 13, and 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.58 Units on a scale
Standard Error 0.41
-2.31 Units on a scale
Standard Error 0.42
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
-4.97 Units on a scale
Standard Error 0.49
-3.11 Units on a scale
Standard Error 0.5
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
-5.83 Units on a scale
Standard Error 0.56
-3.74 Units on a scale
Standard Error 0.57
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
-6.33 Units on a scale
Standard Error 0.59
-4.43 Units on a scale
Standard Error 0.6
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
-6.96 Units on a scale
Standard Error 0.63
-5.66 Units on a scale
Standard Error 0.64
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
-7.02 Units on a scale
Standard Error 0.66
-5.42 Units on a scale
Standard Error 0.67

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.27 Units on a scale
Standard Error 0.42
-2.15 Units on a scale
Standard Error 0.43
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
-4.7 Units on a scale
Standard Error 0.51
-2.94 Units on a scale
Standard Error 0.52
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
-5.77 Units on a scale
Standard Error 0.57
-3.46 Units on a scale
Standard Error 0.59
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
-6.33 Units on a scale
Standard Error 0.61
-4.18 Units on a scale
Standard Error 0.63
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
-6.88 Units on a scale
Standard Error 0.64
-5.25 Units on a scale
Standard Error 0.66
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
-6.97 Units on a scale
Standard Error 0.67
-5.07 Units on a scale
Standard Error 0.69

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=220 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=222 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=213 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-5.47 Units on a scale
Standard Error 0.36
-4.8 Units on a scale
Standard Error 0.37

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 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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=207 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=208 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=198 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-5.36 Units on a scale
Standard Error 0.37
-4.57 Units on a scale
Standard Error 0.39

SECONDARY outcome

Timeframe: 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.

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

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=216 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=220 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=210 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.43 Units on a scale
Standard Error 0.31
-3.33 Units on a scale
Standard Error 0.32

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 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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=204 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=206 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=195 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
-3.35 Units on a scale
Standard Error 0.32
-3.07 Units on a scale
Standard Error 0.33

SECONDARY outcome

Timeframe: Week 8 to 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
3.36 Units on a scale
Standard Deviation 0.68
3.51 Units on a scale
Standard Deviation 0.67
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
3.08 Units on a scale
Standard Deviation 0.85
3.34 Units on a scale
Standard Deviation 0.85
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
2.91 Units on a scale
Standard Deviation 0.82
3.17 Units on a scale
Standard Deviation 0.88
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
2.78 Units on a scale
Standard Deviation 0.87
3.02 Units on a scale
Standard Deviation 0.95
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
2.72 Units on a scale
Standard Deviation 0.87
2.97 Units on a scale
Standard Deviation 1.00
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
2.69 Units on a scale
Standard Deviation 0.89
2.85 Units on a scale
Standard Deviation 1.01

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
2.8 Units on a scale
Standard Deviation 0.86
3.06 Units on a scale
Standard Deviation 0.94
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
3.39 Units on a scale
Standard Deviation 0.65
3.54 Units on a scale
Standard Deviation 0.65
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
3.1 Units on a scale
Standard Deviation 0.82
3.35 Units on a scale
Standard Deviation 0.84
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
2.93 Units on a scale
Standard Deviation 0.8
3.19 Units on a scale
Standard Deviation 0.86
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
2.75 Units on a scale
Standard Deviation 0.86
3.01 Units on a scale
Standard Deviation 0.96
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
2.71 Units on a scale
Standard Deviation 0.88
2.9 Units on a scale
Standard Deviation 0.99

SECONDARY outcome

Timeframe: Weeks 8, 9, 10, 11, 12, 13, and 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
16.9 Percentage of participants
10.1 Percentage of participants
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
18.2 Percentage of participants
15.6 Percentage of participants
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
4.5 Percentage of participants
2.8 Percentage of participants
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
10.2 Percentage of participants
5.05 Percentage of participants
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
13.3 Percentage of participants
8.72 Percentage of participants
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
23.1 Percentage of participants
15.1 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
3.37 Percentage of participants
3.02 Percentage of participants
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
7.58 Percentage of participants
4.93 Percentage of participants
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
13.3 Percentage of participants
8.37 Percentage of participants
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
16.6 Percentage of participants
10.3 Percentage of participants
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
18 Percentage of participants
14.3 Percentage of participants
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
23.2 Percentage of participants
14.3 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 8, 9, 10, 11, 12, 13 and 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=221 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=222 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=214 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
3.15 Percentage of participants
2.8 Percentage of participants
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
4 Percentage of participants
4.13 Percentage of participants
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
8.44 Percentage of participants
5.5 Percentage of participants
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
11.1 Percentage of participants
5.96 Percentage of participants
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
10.7 Percentage of participants
9.17 Percentage of participants
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
15.1 Percentage of participants
11.9 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
1.92 Percentage of participants
3.02 Percentage of participants
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
2.37 Percentage of participants
3.94 Percentage of participants
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
8.06 Percentage of participants
5.42 Percentage of participants
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
10.4 Percentage of participants
6.4 Percentage of participants
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
9.95 Percentage of participants
8.37 Percentage of participants
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
14.7 Percentage of participants
10.8 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 8, 9, 10, 11, 12, 13 and 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.

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

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=226 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=225 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=218 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
9.46 Percentage of participants
6.54 Percentage of participants
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
23.6 Percentage of participants
13.3 Percentage of participants
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
28.4 Percentage of participants
21.6 Percentage of participants
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
35.1 Percentage of participants
29.4 Percentage of participants
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
40 Percentage of participants
28.9 Percentage of participants
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
41.8 Percentage of participants
36.7 Percentage of participants

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Brexpiprazole (3mg) + ADT
n=213 Participants
Participants were administered brexpiprazole 3mg/day as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (1mg) + ADT
n=211 Participants
Participants were administered brexpiprazole 1mg/day as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=203 Participants
Participants were administered placebo daily as an adjunctive therapy to an open label 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
7.69 Percentage of participants
5.53 Percentage of participants
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
21.8 Percentage of participants
12.3 Percentage of participants
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
27.5 Percentage of participants
19.7 Percentage of participants
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
34.1 Percentage of participants
27.6 Percentage of participants
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
38.9 Percentage of participants
27.1 Percentage of participants
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
41.2 Percentage of participants
34 Percentage of participants

Adverse Events

Brexpiprazole (1mg + ADT)

Serious events: 1 serious events
Other events: 63 other events
Deaths: 0 deaths

Brexpiprazole (3mg + ADT)

Serious events: 1 serious events
Other events: 72 other events
Deaths: 0 deaths

Placebo + ADT

Serious events: 0 serious events
Other events: 29 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Brexpiprazole (1mg + ADT)
n=226 participants at risk
Participants were administered brexpiprazole of 1mg as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (3mg + ADT)
n=229 participants at risk
Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=220 participants at risk
Participants were administered placebo as an adjunctive therapy to an open label ADT.
Infections and infestations
Pneumonia
0.44%
1/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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%
0/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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%
0/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
Epilepsy
0.00%
0/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
0.44%
1/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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%
0/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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

Other adverse events
Measure
Brexpiprazole (1mg + ADT)
n=226 participants at risk
Participants were administered brexpiprazole of 1mg as an adjunctive therapy to an assigned open-label ADT.
Brexpiprazole (3mg + ADT)
n=229 participants at risk
Participants were administered brexpiprazole of 3mg as an adjunctive therapy to an assigned open-label ADT.
Placebo + ADT
n=220 participants at risk
Participants were administered placebo as an adjunctive therapy to an open label ADT.
Infections and infestations
Nasopharyngitis
6.6%
15/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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%
7/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
1.8%
4/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
6.6%
15/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
5.7%
13/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
0.91%
2/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
4.4%
10/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
13.5%
31/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
2.3%
5/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
Headache
9.3%
21/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
6.1%
14/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
7.7%
17/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
Somnolence
4.0%
9/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
5.7%
13/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
0.45%
1/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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
Tremor
4.0%
9/226 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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%
12/229 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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.
3.2%
7/220 • AEs were captured from randomization to double-blind treatment at Week 8 to Follow-up 30 (+ 2) days after last dose of study medication.
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 and Commercialization, Inc.

Phone: 800 562-3974

Results disclosure agreements

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