Trial Outcomes & Findings for Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment (NCT NCT01838681)

NCT ID: NCT01838681

Last Updated: 2017-08-09

Results Overview

Full remission is defined as a Montomery and Åsberg Depression Rating Scale (MADRS) total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomized treatment. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1986 participants
• Primary outcome timeframe: From randomisation to end of Period B (24 weeks)
• Results posted on: 2017-08-09

Participant Flow

1986 patients were enrolled; 1982 received open-label ADT plus double-blind placebo in the 8-week Period A. In the 24-week Period B, 886 patients were randomised and 885 were treated with open-label ADT plus double-blind brexpiprazole or placebo. Non-randomised patients continued in Period A+ and received open-label ADT plus double-blind placebo.

Participant milestones

Measure	Period A Placebo and ADT (8 Weeks) Placebo adjunct to open-label treatment with ADT Placebo: Once daily, tablets, orally	Period B Placebo and ADT (24 Weeks Randomised Treatment) Placebo adjunct to open-label treatment with ADT (same ADT as in Period A) Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) Brexpiprazole adjunct to open-label treatment with ADT (same ADT as in Period A) Brexpiprazole: flexible dose; 1, 2, or 3 mg/day, once daily, tablets, orally	Period A+ Placebo and ADT (Non-randomised Patients) Placebo adjunct to open-label treatment with ADT (same ADT as in Period A) Placebo: Once daily, tablets, orally
Period A STARTED	1986	0	0	0
Period A COMPLETED	1661	0	0	0
Period A NOT COMPLETED	325	0	0	0
Period B/A+ STARTED	0	442	444	770
Period B/A+ COMPLETED	0	380	349	653
Period B/A+ NOT COMPLETED	0	62	95	117

Reasons for withdrawal

Measure	Period A Placebo and ADT (8 Weeks) Placebo adjunct to open-label treatment with ADT Placebo: Once daily, tablets, orally	Period B Placebo and ADT (24 Weeks Randomised Treatment) Placebo adjunct to open-label treatment with ADT (same ADT as in Period A) Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) Brexpiprazole adjunct to open-label treatment with ADT (same ADT as in Period A) Brexpiprazole: flexible dose; 1, 2, or 3 mg/day, once daily, tablets, orally	Period A+ Placebo and ADT (Non-randomised Patients) Placebo adjunct to open-label treatment with ADT (same ADT as in Period A) Placebo: Once daily, tablets, orally
Period A Adverse Event	39	0	0	0
Period A Lack of Efficacy	21	0	0	0
Period A Early response	148	0	0	0
Period A Withdrawal by Subject	70	0	0	0
Period A Protocol Violation	16	0	0	0
Period A Non-compliance with IMP	6	0	0	0
Period A Lost to Follow-up	4	0	0	0
Period A Withdrawal before treatment	4	0	0	0
Period A Administrative or other reasons	17	0	0	0
Period B/A+ Adverse Event	0	13	27	16
Period B/A+ Lack of Efficacy	0	9	11	6
Period B/A+ Withdrawal by Subject	0	28	35	47
Period B/A+ Protocol Violation	0	1	4	6
Period B/A+ Non-compliance with IMP	0	2	3	3
Period B/A+ Lost to Follow-up	0	2	5	11
Period B/A+ Withdrawal before treatment	0	1	0	0
Period B/A+ Administrative or other reasons	0	6	10	28

Baseline Characteristics

Brexpiprazole as Adjunctive Treatment in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment

Baseline characteristics by cohort

Measure	All Enrolled Patients n=1986 Participants Period A
Age, Continuous	47.3 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	1402 Participants n=5 Participants
Sex: Female, Male Male	584 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants
Race (NIH/OMB) White	1918 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	46 Participants n=5 Participants
Region of Enrollment Russian Federation	121 participants n=5 Participants
Region of Enrollment Romania	15 participants n=5 Participants
Region of Enrollment United States	78 participants n=5 Participants
Region of Enrollment Ukraine	189 participants n=5 Participants
Region of Enrollment United Kingdom	168 participants n=5 Participants
Region of Enrollment Canada	30 participants n=5 Participants
Region of Enrollment Latvia	84 participants n=5 Participants
Region of Enrollment Sweden	85 participants n=5 Participants
Region of Enrollment Finland	136 participants n=5 Participants
Region of Enrollment Poland	325 participants n=5 Participants
Region of Enrollment Mexico	72 participants n=5 Participants
Region of Enrollment Bulgaria	119 participants n=5 Participants
Region of Enrollment Lithuania	76 participants n=5 Participants
Region of Enrollment Germany	325 participants n=5 Participants
Region of Enrollment Estonia	161 participants n=5 Participants
Region of Enrollment Korea, Republic of	2 participants n=5 Participants

PRIMARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

Full remission is defined as a Montomery and Åsberg Depression Rating Scale (MADRS) total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomized treatment. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Full Remission During the Randomised Treatment Period	110 participants	95 participants

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

Full functional remission is defined as a Sheehan Disability Scale (SDS) total score <=6 and all SDS domain scores <=2 observed for at least 8 consecutive weeks during the randomised treatment period. The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Full Functional Remission During the Randomised Treatment Period	73 participants	68 participants

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

Full global score remission is defined as a Clinical Global Impression - Severity of Illness (CGI-S) score <=2 observed for at least 8 consecutive weeks during the randomised treatment period. The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis, on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Full Global Score Remission During the Randomised Treatment Period	143 participants	121 participants

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The total time the patient spends in remission during randomised treatment. Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score. Time in remission is defined as the sum of days over all periods between Period B visits where remission was obtained. The period between two visits is counted as in remission if the patient was in remission when the period started.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Total Time in Remission During the Randomised Treatment Period	33.5 Number of days Standard Deviation 46.1	30.0 Number of days Standard Deviation 44.3

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The time from randomisation until full remission has been obtained. Full remission is defined as a MADRS total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomised treatment. The time to full remission was calculated using Kaplan-Meier Methods.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Time to Full Remission During the Randomised Treatment Period	NA Days The median number of days to full remission was not estimable (less than 50% of the patients were in full remission).	NA Days The median number of days to full remission was not estimable (less than 50% of the patients were in full remission).

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

Full remission sustained is defined as having obtained full remission and remain in remission until completion of the study. Full remission is defined as a MADRS total score ≤10 and a ≥50% decrease from randomisation in MADRS total score for at least 8 consecutive weeks during randomised treatment.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=441 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=444 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Full Remission Sustained During the Randomised Treatment Period	105 participants	84 participants

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=422 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=422 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period	-5.9 units on a scale Standard Error 0.4	-6.3 units on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). The MADRS total score is the sum of the 10 items.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=361 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=333 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period	-12.6 Units on a scale Standard Error 0.6	-11.5 Units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B. Last Observation Carried Forward (LOCF).

Response is defined as a >=50% decrease from randomisation in MADRS total score.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=440 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=442 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Response at Week 6 During the Randomised Treatment Period	76 participants	82 participants

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B. Last Observation Carried Forward (LOCF).

Response is defined as a >=50% decrease from randomisation in MADRS total score.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=440 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=442 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Response at Week 24 During the Randomised Treatment Period	236 participants	223 participants

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B. Last Observation Carried Forward (LOCF).

Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=440 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=442 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Remission at Week 6 During the Randomised Treatment Period	46 participants	53 participants

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B. Last Observation Carried Forward (LOCF).

Remission is defined as a MADRS total score <=10 and a >=50% decrease from randomisation in MADRS total score.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=440 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=442 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Remission at Week 24 in the Randomised Treatment Period	198 participants	176 participants

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B

The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=422 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=421 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 6 in SDS Total Score During the Randomised Treatment Period	-3.0 units on a scale Standard Error 0.3	-2.9 units on a scale Standard Error 0.3

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The SDS assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=361 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=333 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 24 in SDS Total Score During the Randomised Treatment Period	-6.7 units on a scale Standard Error 0.5	-5.5 units on a scale Standard Error 0.5

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=422 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=422 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 6 in CGI-S Score During the Randomised Treatment Period	-0.8 units on a scale Standard Error 0.1	-0.8 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The CGI-S is a 7-point scale where the clinician rates the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=361 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=333 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 24 in CGI-S Score During the Randomised Treatment Period	-1.7 units on a scale Standard Error 0.1	-1.5 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: From randomisation to week 6

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The original Q-LES-Q is a patient self-rated scale designed to measure the degree of enjoyment and satisfaction experienced by patients in various areas of daily life. It consists of 93 items to measure: physical health, feelings, work, household duties, school, leisure time activities, social relations, and general activities. The Q-LES-Q short form (SF) contains 16 items from the general activities section. Each item is rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total score is the sum of the first 14 items. The last two scores are stand-alone items. The total score ranges from 14 to 70.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=422 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=421 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period	3.5 units on a scale Standard Error 0.4	3.2 units on a scale Standard Error 0.4

SECONDARY outcome

Timeframe: From randomisation to end of Period B (24 weeks)

Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.

The original Q-LES-Q is a patient self-rated scale designed to measure the degree of enjoyment and satisfaction experienced by patients in various areas of daily life. It consists of 93 items to measure: physical health, feelings, work, household duties, school, leisure time activities, social relations, and general activities. The Q-LES-Q short form (SF) contains 16 items from the general activities section. Each item is rated on a 5-point scale ranging from 1 (very poor) to 5 (very good). The total score is the sum of the first 14 items. The last two scores are stand-alone items. The total score ranges from 14 to 70.

Outcome measures

Measure	Period B Placebo and ADT (24 Weeks Randomised Treatment) n=361 Participants Placebo adjunct to open-label treatment with a commercially available ADT Placebo: Once daily, tablets, orally	Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) n=333 Participants Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, or 3 mg/day, once daily dose, tablets, orally
Change From Randomisation to Week 24 in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q (SF)) Total Score During the Randomised Treatment Period	7.7 units on a scale Standard Error 0.7	6.2 units on a scale Standard Error 0.7

Adverse Events

Placebo and ADT

Serious events: 13 serious events

Other events: 97 other events

Deaths: 0 deaths

Brexpiprazole and ADT

Serious events: 9 serious events

Other events: 108 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo and ADT n=441 participants at risk Placebo adjunct to open-label treatment with a commercially available antidepressant (ADT) Placebo: Once daily, tablets, orally	Brexpiprazole and ADT n=444 participants at risk Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, 3, mg/day, once daily, tablets, orally
Gastrointestinal disorders Pancreatitis	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Infections and infestations Influenza	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Injury, poisoning and procedural complications Forearm fracture	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Injury, poisoning and procedural complications Intentional overdose	0.45% 2/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Injury, poisoning and procedural complications Radius fracture	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Investigations False positive investigation result	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Metabolism and nutrition disorders Obesity	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Dizziness	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Loss of consciousness	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Ruptured cerebral aneurysm	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Sciatica	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Seizure	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Psychiatric disorders Major depression	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Psychiatric disorders Self injurious behaviour	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Psychiatric disorders Suicidal ideation	0.68% 3/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.45% 2/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Psychiatric disorders Suicide attempt	0.23% 1/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Reproductive system and breast disorders Ovarian cyst	0.33% 1/302 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.00% 0/307 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Social circumstances Family stress	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Vascular disorders Circulatory collapse	0.00% 0/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	0.23% 1/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section

Other adverse events

Measure	Placebo and ADT n=441 participants at risk Placebo adjunct to open-label treatment with a commercially available antidepressant (ADT) Placebo: Once daily, tablets, orally	Brexpiprazole and ADT n=444 participants at risk Brexpiprazole adjunct to open-label treatment with a commercially available ADT Brexpiprazole: 1, 2, 3, mg/day, once daily, tablets, orally
Infections and infestations Nasopharyngitis	7.7% 34/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	6.3% 28/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Injury, poisoning and procedural complications Accidental overdose	5.7% 25/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	6.1% 27/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Investigations Weight increased	5.0% 22/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	9.5% 42/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section
Nervous system disorders Headache	7.0% 31/441 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section	7.7% 34/444 • Randomisation to end of study (28 weeks) Treatment-Emergent Adverse Events are reported in this section

Additional Information

Email contact via

H. Lundbeck A/S

Email: LundbeckClinicalTrials@lundbeck.com

Results disclosure agreements

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