Major Depressive Disorder
Conditions
Brief summary
To evaluate the long-term efficacy and safety of brexpiprazole as an adjunctive treatment to an antidepressant treatment (ADT) for adult patients with Major Depressive Disorder (MDD).
Detailed description
The total duration of the study was 32 weeks and the study consisted of Periods A, B, and A+. Patients entered the study in Period A and were treated open-label with one of six commercially available antidepressant treatments (ADTs) for 8 weeks. Patients who met the blinded response criteria at the Week 6 Visit, were deemed early responders and were withdrawn from the study. At Week 8, patients with inadequate response to placebo + ADT, as per the randomisation criteria, entered Period B and were randomised to received double-blind brexpiprazole + ADT or placebo + ADT for 24 weeks. Non-randomised patients continued in Period A+ and received placebo + ADT until the end of the study. The primary objective was to compare the efficacy and safety of brexpiprazole with placebo. This comparison occurred Period B; therefore, the focus is Period B.
Interventions
DRUGPlacebo
Once daily, tablets, orally
DRUGBrexpiprazole
1, 2, or 3 mg/day, once daily dose, tablets, orally. Uptitration in weekly steps from 1 mg/day
DRUGADT
Duloxetine, escitalopram, fluoxetine, paroxetine IR, sertraline, venlafaxine XR; dosing according to label
Sponsors
Otsuka Pharmaceutical Co., Ltd.
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The patient is an outpatient consulting a psychiatrist. * The patient has an MDD diagnosed according to DSM-IV-TR™. The current Major Depressive Episode (MDE) should be confirmed using the Mini International Neuropsychiatric Interview (MINI). * The patient has a moderate to severe depression and an insufficient response to at least one and no more than three adequate antidepressant treatments. * The patient agrees to protocol-defined use of effective contraception.
Exclusion criteria
* The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™ criteria), established as the primary diagnosis, other than MDD. * The patient has a current Axis II (DSM-IV-TR™) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypical or histrionic personality disorder. * The patient has experienced/experiences hallucinations, delusions or any psychotic symptomatology in the current MDE. * The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria). * The patient, in the opinion of the investigator or according to Columbia-Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide. * The patient has had neuroleptic malignant syndrome. * The patient has any relevant medical history or current presence of systemic disease. * The patient has, at the Screening Visit an abnormal ECG that is, in the investigator's opinion, clinically significant. * The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for \>5 years prior to the first dose of IMP. * The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Full Remission During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Full Global Score Remission During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Total Time in Remission During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Time to Full Remission During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Full Remission Sustained During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period | From randomisation to week 6 | 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. |
| Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Response at Week 6 During the Randomised Treatment Period | From randomisation to week 6 | Response is defined as a \>=50% decrease from randomisation in MADRS total score. |
| Response at Week 24 During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | Response is defined as a \>=50% decrease from randomisation in MADRS total score. |
| Full Functional Remission During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Remission at Week 24 in the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | Remission is defined as a MADRS total score \<=10 and a \>=50% decrease from randomisation in MADRS total score. |
| Change From Randomisation to Week 6 in SDS Total Score During the Randomised Treatment Period | From randomisation to week 6 | 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. |
| Change From Randomisation to Week 24 in SDS Total Score During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Change From Randomisation to Week 6 in CGI-S Score During the Randomised Treatment Period | From randomisation to week 6 | 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. |
| Change From Randomisation to Week 24 in CGI-S Score During the Randomised Treatment Period | From randomisation to end of Period B (24 weeks) | 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. |
| Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period | From randomisation to week 6 | 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. |
| 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 | From randomisation to end of Period B (24 weeks) | 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. |
| Remission at Week 6 During the Randomised Treatment Period | From randomisation to week 6 | Remission is defined as a MADRS total score \<=10 and a \>=50% decrease from randomisation in MADRS total score. |
Countries
Bulgaria, Canada, Estonia, Finland, Germany, Latvia, Lithuania, Mexico, Poland, Romania, Russia, South Korea, Sweden, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Patients Period A | 1,986 |
| Total | 1,986 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period A | Administrative or other reasons | 17 | 0 | 0 | 0 |
| Period A | Adverse Event | 39 | 0 | 0 | 0 |
| Period A | Early response | 148 | 0 | 0 | 0 |
| Period A | Lack of Efficacy | 21 | 0 | 0 | 0 |
| Period A | Lost to Follow-up | 4 | 0 | 0 | 0 |
| Period A | Non-compliance with IMP | 6 | 0 | 0 | 0 |
| Period A | Protocol Violation | 16 | 0 | 0 | 0 |
| Period A | Withdrawal before treatment | 4 | 0 | 0 | 0 |
| Period A | Withdrawal by Subject | 70 | 0 | 0 | 0 |
| Period B/A+ | Administrative or other reasons | 0 | 6 | 10 | 28 |
| Period B/A+ | Adverse Event | 0 | 13 | 27 | 16 |
| Period B/A+ | Lack of Efficacy | 0 | 9 | 11 | 6 |
| Period B/A+ | Lost to Follow-up | 0 | 2 | 5 | 11 |
| Period B/A+ | Non-compliance with IMP | 0 | 2 | 3 | 3 |
| Period B/A+ | Protocol Violation | 0 | 1 | 4 | 6 |
| Period B/A+ | Withdrawal before treatment | 0 | 1 | 0 | 0 |
| Period B/A+ | Withdrawal by Subject | 0 | 28 | 35 | 47 |
Baseline characteristics
| Characteristic | All Enrolled Patients |
|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 46 Participants |
| Race (NIH/OMB) White | 1918 Participants |
| Region of Enrollment Bulgaria | 119 participants |
| Region of Enrollment Canada | 30 participants |
| Region of Enrollment Estonia | 161 participants |
| Region of Enrollment Finland | 136 participants |
| Region of Enrollment Germany | 325 participants |
| Region of Enrollment Korea, Republic of | 2 participants |
| Region of Enrollment Latvia | 84 participants |
| Region of Enrollment Lithuania | 76 participants |
| Region of Enrollment Mexico | 72 participants |
| Region of Enrollment Poland | 325 participants |
| Region of Enrollment Romania | 15 participants |
| Region of Enrollment Russian Federation | 121 participants |
| Region of Enrollment Sweden | 85 participants |
| Region of Enrollment Ukraine | 189 participants |
| Region of Enrollment United Kingdom | 168 participants |
| Region of Enrollment United States | 78 participants |
| Sex: Female, Male Female | 1402 Participants |
| Sex: Female, Male Male | 584 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 97 / 441 | 108 / 444 |
| serious Total, serious adverse events | 13 / 441 | 9 / 444 |
Outcome results
Primary
Full Remission During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Full Remission During the Randomised Treatment Period | 110 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Full Remission During the Randomised Treatment Period | 95 participants |
p-value: 0.264195% CI: [0.6, 1.15]Regression, Logistic
Secondary
Change From Randomisation to Week 24 in CGI-S Score 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 24 in CGI-S Score During the Randomised Treatment Period | -1.5 units on a scale | Standard Error 0.1 |
Secondary
Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 24 in MADRS Total Score During the Randomised Treatment Period | -11.5 Units on a scale | Standard Error 0.6 |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 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 | 6.2 units on a scale | Standard Error 0.7 |
Secondary
Change From Randomisation to Week 24 in SDS Total Score 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 24 in SDS Total Score During the Randomised Treatment Period | -5.5 units on a scale | Standard Error 0.5 |
Secondary
Change From Randomisation to Week 6 in CGI-S Score 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.
Time frame: From randomisation to week 6
Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | 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 |
Secondary
Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period
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.
Time frame: From randomisation to week 6
Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 6 in MADRS Total Score During the Randomised Treatment Period | -6.3 units on a scale | Standard Error 0.4 |
Secondary
Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period
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.
Time frame: From randomisation to week 6
Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 6 in Q-LES-Q (SF) Total Score During the Randomised Treatment Period | 3.2 units on a scale | Standard Error 0.4 |
Secondary
Change From Randomisation to Week 6 in SDS Total Score 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.
Time frame: From randomisation to week 6
Population: All randomised patients who took at least one dose of randomised treatment (brexpiprazole or placebo) in Period B
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | 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 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Change From Randomisation to Week 6 in SDS Total Score During the Randomised Treatment Period | -2.9 units on a scale | Standard Error 0.3 |
Secondary
Full Functional Remission During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Full Functional Remission During the Randomised Treatment Period | 73 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Full Functional Remission During the Randomised Treatment Period | 68 participants |
Secondary
Full Global Score Remission During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Full Global Score Remission During the Randomised Treatment Period | 143 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Full Global Score Remission During the Randomised Treatment Period | 121 participants |
Secondary
Full Remission Sustained During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Full Remission Sustained During the Randomised Treatment Period | 105 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Full Remission Sustained During the Randomised Treatment Period | 84 participants |
Secondary
Remission at Week 24 in the Randomised Treatment Period
Remission is defined as a MADRS total score \<=10 and a \>=50% decrease from randomisation in MADRS total score.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Remission at Week 24 in the Randomised Treatment Period | 198 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Remission at Week 24 in the Randomised Treatment Period | 176 participants |
Secondary
Remission at Week 6 During the Randomised Treatment Period
Remission is defined as a MADRS total score \<=10 and a \>=50% decrease from randomisation in MADRS total score.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Remission at Week 6 During the Randomised Treatment Period | 46 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Remission at Week 6 During the Randomised Treatment Period | 53 participants |
Secondary
Response at Week 24 During the Randomised Treatment Period
Response is defined as a \>=50% decrease from randomisation in MADRS total score.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Response at Week 24 During the Randomised Treatment Period | 236 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Response at Week 24 During the Randomised Treatment Period | 223 participants |
Secondary
Response at Week 6 During the Randomised Treatment Period
Response is defined as a \>=50% decrease from randomisation in MADRS total score.
Time frame: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Response at Week 6 During the Randomised Treatment Period | 76 participants |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Response at Week 6 During the Randomised Treatment Period | 82 participants |
Secondary
Time to Full Remission During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Time to Full Remission During the Randomised Treatment Period | NA Days |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Time to Full Remission During the Randomised Treatment Period | NA Days |
Secondary
Total Time in Remission During the Randomised Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Period B Placebo and ADT (24 Weeks Randomised Treatment) | Total Time in Remission During the Randomised Treatment Period | 33.5 Number of days | Standard Deviation 46.1 |
| Period B Brexpiprazole and ADT (24 Weeks Randomised Treatment) | Total Time in Remission During the Randomised Treatment Period | 30.0 Number of days | Standard Deviation 44.3 |