Depression, Depressive Disorder, Depressive Disorder, Major, Mental Disorders, Mood Disorders
Conditions
Keywords
OPC-34712, brexpiprazole, Major Depressive Disorder, Adjunctive Treatment
Brief summary
To compare the effect of OPC-34712 (brexpiprazole) to the effect of placebo (an inactive substance) as add on treatment to an assigned FDA approved antidepressant treatment (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective trial of the same assigned FDA approved ADT
Interventions
DRUGOPC-34712 + ADT
Tablet, Oral, 2 mg OPC-34712 and FDA Approved Antidepressant Therapy (ADT)
DRUGPlacebo + ADT
Placebo + FDA Approved Antidepressant (ADT)
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects between 18 and 65 years of age, with diagnosis of major depressive disorder, as defined by DSM-IV-TR criteria * The current depressive episode must be equal to or greater than 8 weeks in duration * Subjects must report a history for the current depressive episode of an inadequate response to no more than three adequate antidepressant treatments
Exclusion criteria
* Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug * Subjects who report an inadequate response to more than three adequate trials of antidepressant treatments during current depressive episode at a therapeutic dose for an adequate duration. * Subjects with a current Axis I (DSM-IV-TR) diagnosis of: Delirium, dementia, amnestic or other cognitive disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder, Bipolar I or II disorder * Subjects with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample. | Baseline and Week 14 | The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 9, 10, 11, 12, and 13 | The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9, 10, 11, 12, and 13 | The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place. |
| Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 9, 10, 11, 12, 13, and 14 | The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8). |
| Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9, 10, 11, 12, 13, and 14 | The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8). |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 9, 10, 11, 12, 13, and 14 | Items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 9, 10, 11, 12, 13, and 14 | Items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 9, 10, 11, 12, 13, and 14 | The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the best rating and the highest score (2 or 4) is the worst rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 9, 10, 11, 12, 13, and 14 | The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84. |
| Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Week 11 and 14 | The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. |
| Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample. | Baseline and Week 14 | The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample. | Baseline and Week 14 | The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the best rating and the highest score (2 or 4) is the worst rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample | Baseline and Week 14 | The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the best rating and 4 is the worst rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher scores indicating worse anxiety symptoms. |
| Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | The HAM-A is utilized for the evaluation of anxiety symptoms. The HAM-A consists of 14 items. Each item is rated on a 0 to 4 scale. For all of these items, 0 is the best rating and 4 is the worst rating. If no item scores are missing, then the HAM-A total score is the sum of all 14 item scores. The possible total scores are from 0 to 56, with higher scores indicating worse anxiety symptoms. |
| Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | Baseline and Week 14 | The MADRS response was defined as \>/=50% reduction in MADRS total score from end of Phase A (Week 8). |
| Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | The MADRS response was defined as \>/=50% reduction in MADRS total score from end of Phase A (Week 8). |
| Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | Baseline and Week 14 | MADRS remission was defined as \</=10 and \>/=50% reduction in MADRS total score from end of Phase A (Week 8). |
| Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | MADRS remission was defined as \</=10 and \>/=50% reduction in MADRS total score from end of Phase A (Week 8). |
| Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | Baseline and Week 14 | CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). |
| Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | Baseline and Week 14 | CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved). |
| Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Week 11 and 14 | The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. |
| Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol | Baseline and Week 14 | The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable. |
Countries
Canada, France, Poland, Slovakia, United States
Participant flow
Recruitment details
This trial was conducted in 826 subjects at 59 trial sites in the following 5 countries: United States, Canada, Poland, Slovakia, and France.
Pre-assignment details
The study consisted of a 7 to 28-day Screening period, an 8-Week single-blind placebo + ADT prospective Phase-A, a 6-Week double-blind randomization Phase-B or single-blind Phase A+ and a Follow-up of 30 (+2) days after the last dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 2 mg/Day + ADT Participants received Brexpiprazole 2 mg/day as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit. | 188 |
| Double-blind Placebo + ADT Participants received placebo as an adjunctive therapy over a 2-week period beginning at the Week 8 visit and continued to take the same ADT that was assigned in Phase A at the final dose taken just prior to the Week 8 visit. | 191 |
| Total | 379 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Phase A+ | Adverse Event | 0 | 0 | 0 | 2 |
| Phase A+ | Lost to Follow-up | 0 | 0 | 0 | 7 |
| Phase A+ | Met Withdrawal Criteria | 0 | 0 | 0 | 4 |
| Phase A+ | Physician Decision | 0 | 0 | 0 | 2 |
| Phase A+ | Protocol Deviation | 0 | 0 | 0 | 4 |
| Phase A+ | Withdrawal by Subject | 0 | 0 | 0 | 5 |
| Phase B (6 Weeks) | Adverse Event | 0 | 6 | 0 | 0 |
| Phase B (6 Weeks) | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Phase B (6 Weeks) | Met Withdrawal Criteria | 0 | 3 | 2 | 0 |
| Phase B (6 Weeks) | Protocol Deviation | 0 | 1 | 3 | 0 |
| Phase B (6 Weeks) | Withdrawal by Subject | 0 | 3 | 8 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Adverse Event | 19 | 0 | 0 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Lost to Follow-up | 16 | 0 | 0 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Met Withdrawal Criteria | 16 | 0 | 0 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Physician Decision | 5 | 0 | 0 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Protocol Deviation | 24 | 0 | 0 | 0 |
| Placebo+ADT Prospective Phase-A(8 Weeks) | Withdrawal by Subject | 34 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-blind Placebo + ADT | Total | Brexpiprazole 2 mg/Day + ADT |
|---|---|---|---|
| Age, Continuous | 45.2 Years STANDARD_DEVIATION 11.3 | 44.6 Years STANDARD_DEVIATION 11.5 | 44.1 Years STANDARD_DEVIATION 11.6 |
| Sex: Female, Male Female | 137 Participants | 267 Participants | 130 Participants |
| Sex: Female, Male Male | 54 Participants | 112 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 188 | 27 / 191 |
| serious Total, serious adverse events | 2 / 188 | 2 / 191 |
Outcome results
Primary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol.
The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
Time frame: Baseline and Week 14
Population: All participants in the Efficacy Sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol. | -8.36 Units on a scale | Standard Error 0.64 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol. | -5.15 Units on a scale | Standard Error 0.63 |
p-value: 0.000295% CI: [-4.87, -1.54]Mixed Models Analysis
Primary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample.
The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample. | -8.27 Units on a scale | Standard Error 0.61 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score for the Efficacy Sample. | -5.15 Units on a scale | Standard Error 0.6 |
Comparison: The primary analysis was performed on the Efficacy Sample by fitting a Mixed Model Repeated Measures (MMRM) analysis with an unstructured variance covariance structure in which the change from the end of Phase A (Week 8) in MADRS Total Score (at Weeks 9 to 14) was the dependent variable. The model included fixed class effect terms for treatment, trial site, visit week, and an interaction term of treatment by visit week.p-value: 0.000195% CI: [-4.7, -1.54]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample.
The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Time frame: Week 11 and 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Work/School: Week 11 | -0.70 Units on a scale | Standard Error 0.21 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Work/School: Week 14 | -1.09 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Social life: Week 11 | -1.17 Units on a scale | Standard Error 0.17 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Social life: Week 14 | -1.54 Units on a scale | Standard Error 0.19 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Family life: Week 11 | -1.06 Units on a scale | Standard Error 0.18 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Family life: Week 14 | -1.33 Units on a scale | Standard Error 0.19 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Family life: Week 11 | -0.43 Units on a scale | Standard Error 0.18 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Work/School: Week 11 | -0.42 Units on a scale | Standard Error 0.22 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Social life: Week 14 | -1.04 Units on a scale | Standard Error 0.18 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Work/School: Week 14 | -0.90 Units on a scale | Standard Error 0.22 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Family life: Week 14 | -0.73 Units on a scale | Standard Error 0.19 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample. | Item: Social life: Week 11 | -0.67 Units on a scale | Standard Error 0.17 |
Comparison: For Item: Work/School: Week 11p-value: 0.307995% CI: [-0.81, 0.26]Mixed Models Analysis
Comparison: For Item: Work/School: Week 14p-value: 0.477195% CI: [-0.73, 0.34]Mixed Models Analysis
Comparison: For Item: Social life: Week 11p-value: 0.019595% CI: [-0.92, -0.08]Mixed Models Analysis
Comparison: For Item: Social life: Week 14p-value: 0.032395% CI: [-0.96, -0.04]Mixed Models Analysis
Comparison: For Item: Family life: Week 11p-value: 0.005895% CI: [-1.07, -0.18]Cochran-Mantel-Haenszel
Comparison: For Item: Family life: Week 14p-value: 0.012995% CI: [-1.07, -0.13]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol.
The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Time frame: Week 11 and 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Work/School: Week 11 | -0.76 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Work/School: Week 14 | -1.11 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Social life: Week 11 | -1.18 Units on a scale | Standard Error 0.18 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Social life: Week 14 | -1.57 Units on a scale | Standard Error 0.19 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Family life: Week 11 | -0.99 Units on a scale | Standard Error 0.19 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Family life: Week 14 | -0.43 Units on a scale | Standard Error 0.18 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Family life: Week 11 | -0.43 Units on a scale | Standard Error 0.18 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Work/School: Week 11 | -0.58 Units on a scale | Standard Error 0.22 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Social life: Week 14 | -1.02 Units on a scale | Standard Error 0.19 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Work/School: Week 14 | -0.96 Units on a scale | Standard Error 0.23 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Family life: Week 14 | -0.70 Units on a scale | Standard Error 0.19 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol. | Item: Social life: Week 11 | -0.69 Units on a scale | Standard Error 0.18 |
Comparison: Statistical analysis for Item: Work/School Week 11p-value: 0.515195% CI: [-0.71, 0.36]Mixed Models Analysis
Comparison: Statistical analysis for Item: Work/School Week 14p-value: 0.60895% CI: [-0.7, 0.41]Mixed Models Analysis
Comparison: Statistical analysis for Item: Social life-Week 11p-value: 0.026795% CI: [-0.92, -0.06]Mixed Models Analysis
Comparison: Statistical analysis for Item: Social life-Week 14p-value: 0.022495% CI: [-1.01, -0.08]Mixed Models Analysis
Comparison: Statistical analysis for Item: Family life-Week 11p-value: 0.014695% CI: [-1.01, -0.11]Mixed Models Analysis
Comparison: Statistical analysis for Item: Family life-Week 14p-value: 0.011395% CI: [-1.09, -0.14]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol.
Items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 10 | -0.43 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 12 | -0.70 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 9 | -0.24 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 13 | -0.85 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 14 | -0.91 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 11 | -0.58 Units on a scale | Standard Error 0.06 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 14 | -0.57 Units on a scale | Standard Error 0.07 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 9 | -0.09 Units on a scale | Standard Error 0.05 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 10 | -0.32 Units on a scale | Standard Error 0.06 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 11 | -0.42 Units on a scale | Standard Error 0.06 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 12 | -0.46 Units on a scale | Standard Error 0.07 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in CGI-S Scale Score for the Efficacy Sample Per the Final Protocol. | Week 13 | -0.50 Units on a scale | Standard Error 0.07 |
Comparison: Statistical analysis for Week 9p-value: 0.010995% CI: [-0.27, -0.04]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.128695% CI: [-0.25, 0.03]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.052195% CI: [-0.32, 0]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.008495% CI: [-0.42, -0.06]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 0.000395% CI: [-0.54, -0.16]Mixed Models Analysis
Comparison: Statistical analysis for Week 14p-value: 0.000695% CI: [-0.53, -0.15]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample.
Items on CGI-S scale are: 0 = not assessed, 1 = normal, not at all ill, 2 = borderline mentally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill patients. The score 0 (= not assessed) will be set to missing. The CGI-S is therefore a 7-point scale from 1 through 7.
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 9 | -0.25 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 10 | -0.45 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 11 | -0.61 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 12 | -0.70 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 13 | -0.86 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 14 | -0.91 Units on a scale | Standard Error 0.07 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 13 | -0.50 Units on a scale | Standard Error 0.07 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 9 | -0.12 Units on a scale | Standard Error 0.05 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 12 | -0.45 Units on a scale | Standard Error 0.06 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 10 | -0.31 Units on a scale | Standard Error 0.05 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 14 | -0.58 Units on a scale | Standard Error 0.07 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Clinical Global Impression - Severity of Illness (CGI-S) Scale Score for the Efficacy Sample. | Week 11 | -0.40 Units on a scale | Standard Error 0.06 |
Comparison: Statistical analysis for Week 9p-value: 0.022995% CI: [-0.25, -0.02]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.045995% CI: [-0.28, 0]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.009795% CI: [-0.37, -0.05]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.003895% CI: [-0.42, -0.08]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 0.000195% CI: [-0.54, -0.18]Mixed Models Analysis
Comparison: Statistical analysis for Week 14.p-value: 0.000495% CI: [-0.52, -0.15]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.
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.
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | -3.79 Units on a scale | Standard Error 0.45 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-A Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | -2.70 Units on a scale | Standard Error 0.43 |
p-value: 0.037695% CI: [-2.13, -0.06]ANCOVA
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol.
The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the best rating and the highest score (2 or 4) is the worst rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at Phase B visit, if no observation was recorded, data was carried forward from previous visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | -5.89 Units on a scale | Standard Error 0.51 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in HAM-D Rating Scale Total Score for the Efficacy Sample Per the Final Protocol. | -3.59 Units on a scale | Standard Error 0.49 |
p-value: 0.000295% CI: [-3.47, -1.12]ANCOVA
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample
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.
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample | -3.94 Units on a scale | Standard Error 0.43 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Anxiety (HAM-A) Rating Scale Total Score for the Efficacy Sample | -2.77 Units on a scale | Standard Error 0.42 |
Comparison: ANCOVA\_LOCF model with treatment and trial site as main effects, and baseline (end of Phase A \[Week 8\]) value as a covariate was used.p-value: 0.021995% CI: [-2.17, -0.17]ANCOVA
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample.
The HAM-D (17-Item) consists of 17 items. Eight items are rated on a 0 to 2 scale (items 4, 5, 6, 12, 13, 14, 16 and 17), while nine items (items 1, 2, 3, 7, 8, 9, 10, 11, and 15) are rated on a 0 to 4 scale (twice the weight of the other items). For all of these items, 0 is the best rating and the highest score (2 or 4) is the worst rating. The sum of the scores from the first 17 items; 0-7 =Normal; 8-13 =mild depression; 14-18 =moderate depression; 19-22 =severe depression; ≥23 =very severe depression. The total score ranges from 0 to 52, with higher score indicating worse depressive symptoms.
Time frame: Baseline and Week 14
Population: Efficacy Sample comprised all participants in Safety Sample who had end of Phase A value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The Last-observation-carried-forward (LOCF) data set included data recorded at Phase B visit, if no observation was recorded, data was carried forward from previous visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample. | -5.89 Units on a scale | Standard Error 0.48 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in Hamilton Depression (HAM-D) Rating Scale Total Score for the Efficacy Sample. | -3.55 Units on a scale | Standard Error 0.47 |
Comparison: ANCOVA\_Last observation carry forward (LOCF) model with treatment and trial site as main effects, and baseline (end of Phase A \[Week 8\]) value as a covariate was used.p-value: 0.000195% CI: [-3.47, -1.22]ANCOVA
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample.
The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
Time frame: Week 9, 10, 11, 12, and 13
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 10 | -5.15 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 12 | -7.22 Units on a scale | Standard Error 0.55 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 11 | -6.69 Units on a scale | Standard Error 0.52 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 13 | -8.28 Units on a scale | Standard Error 0.58 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 9 | -3.15 Units on a scale | Standard Error 0.4 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 13 | -5.10 Units on a scale | Standard Error 0.57 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 9 | -1.86 Units on a scale | Standard Error 0.39 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 10 | -3.43 Units on a scale | Standard Error 0.47 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 11 | -4.06 Units on a scale | Standard Error 0.52 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample. | Week 12 | -4.63 Units on a scale | Standard Error 0.54 |
Comparison: Statistical analysis for Week 9p-value: 0.00895% CI: [-2.25, -0.34]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.004595% CI: [-2.91, -0.54]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.000195% CI: [-3.96, -1.3]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.000495% CI: [-4.01, -1.18]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 095% CI: [-4.68, -1.7]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol.
The MADRS consists of 10 items, all rated on a 0 to 6 scale with 0 being the best rating and 6 being the worst rating. The MADRS total score is the sum of ratings for all 10 items. The possible total scores are from 0 to 60. The MADRS total score will be un-evaluable if less than 8 of the 10 items are recorded. If 8 or 9 of the 10 items are recorded, the MADRS total score will be the mean of the recorded items multiplied by 10 and then rounded to the first decimal place.
Time frame: Week 9, 10, 11, 12, and 13
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 10 | -5.04 Units on a scale | Standard Error 0.49 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 12 | -7.24 Units on a scale | Standard Error 0.58 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 11 | -6.58 Units on a scale | Standard Error 0.54 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 13 | -8.28 Units on a scale | Standard Error 0.61 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9 | -3.05 Units on a scale | Standard Error 0.41 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 13 | -5.01 Units on a scale | Standard Error 0.6 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9 | -1.74 Units on a scale | Standard Error 0.41 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 10 | -3.52 Units on a scale | Standard Error 0.48 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 11 | -4.17 Units on a scale | Standard Error 0.53 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 12 | -4.72 Units on a scale | Standard Error 0.57 |
Comparison: Statistical analysis for Week 9p-value: 0.008695% CI: [-2.28, -0.34]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.014995% CI: [-2.74, -0.3]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.000695% CI: [-3.78, -1.05]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.000995% CI: [-4, -1.04]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 095% CI: [-4.84, -3.28]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol.
The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84.
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 9 | -3.30 Units on a scale | Standard Error 0.53 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 10 | -4.29 Units on a scale | Standard Error 0.61 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 11 | -5.45 Units on a scale | Standard Error 0.67 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 12 | -6.32 Units on a scale | Standard Error 0.71 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 13 | -7.03 Units on a scale | Standard Error 0.74 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 14 | -7.59 Units on a scale | Standard Error 0.77 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 13 | -5.60 Units on a scale | Standard Error 0.73 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 9 | -1.59 Units on a scale | Standard Error 0.51 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 12 | -5.06 Units on a scale | Standard Error 0.7 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 10 | -3.13 Units on a scale | Standard Error 0.6 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 14 | -6.05 Units on a scale | Standard Error 0.75 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the IDS-SR Total Score for the Efficacy Sample Per the Final Protocol. | Week 11 | -4.73 Units on a scale | Standard Error 0.66 |
Comparison: Statistical analysis for Week 9p-value: 0.006995% CI: [-2.95, -0.47]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.132295% CI: [-2.68, 0.35]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.405595% CI: [-2.41, 0.98]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.171595% CI: [-3.08, 0.55]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 0.142495% CI: [-3.33, 0.48]Mixed Models Analysis
Comparison: Statistical analysis for Week 14p-value: 0.12795% CI: [-3.52, 0.44]Mixed Models Analysis
Secondary
Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample.
The IDS-SR consists of 30 items, all rated on a 0 to 3 scale with 0 being the best rating and 3 being the worst rating. Besides item 9, two sub-items 9A and 9B exist, with possible scores of 1, 2 or 3 for item 9A, and 0 or 1 for item 9B. The scores for these two sub-items are not included in the calculation of the total score. Item 11 or item 12 should be completed but not both, and similarly, item 13 or item 14 should be completed but not both. Should items 11 and 12 be rated both, then the maximum of the two scores will be used. The same approach will be used for handling items 13 and 14. The IDS-SR total score is the sum of ratings of 28 item scores. The possible IDS-SR total score ranges from 0 to 84.
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 9 | -3.02 Units on a scale | Standard Error 0.52 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 10 | -4.17 Units on a scale | Standard Error 0.59 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 11 | -5.41 Units on a scale | Standard Error 0.65 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 12 | -6.16 Units on a scale | Standard Error 0.68 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 13 | -7.00 Units on a scale | Standard Error 0.72 |
| Brexpiprazole 2 mg/Day + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 14 | -7.49 Units on a scale | Standard Error 0.74 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 13 | -5.25 Units on a scale | Standard Error 0.71 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 9 | -1.45 Units on a scale | Standard Error 0.51 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 12 | -4.69 Units on a scale | Standard Error 0.67 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 10 | -2.64 Units on a scale | Standard Error 0.59 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 14 | -5.52 Units on a scale | Standard Error 0.73 |
| Double-blind Placebo + ADT | Change From Baseline (End of Phase A [Week 8]) to Week 14 in the Inventory of Depressive Symptomatology (Self-Report) (IDS-SR) Total Score for the Efficacy Sample. | Week 11 | -4.31 Units on a scale | Standard Error 0.64 |
Comparison: Statistical analysis for Week 9p-value: 0.013995% CI: [-2.82, -0.32]Mixed Models Analysis
Comparison: Statistical analysis for Week 10p-value: 0.043695% CI: [-3.01, -0.04]Mixed Models Analysis
Comparison: Statistical analysis for Week 11p-value: 0.190395% CI: [-2.75, 0.55]Mixed Models Analysis
Comparison: Statistical analysis for Week 12p-value: 0.095195% CI: [-3.21, 0.26]Mixed Models Analysis
Comparison: Statistical analysis for Week 13p-value: 0.062695% CI: [-3.59, 0.09]Mixed Models Analysis
Comparison: Statistical analysis for Week 14p-value: 0.043595% CI: [-3.87, -0.06]Mixed Models Analysis
Secondary
Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol.
The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8).
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9 | 3.44 Units on a scale | Standard Deviation 0.81 |
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 10 | 3.21 Units on a scale | Standard Deviation 0.89 |
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 11 | 3.07 Units on a scale | Standard Deviation 1.01 |
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 12 | 2.85 Units on a scale | Standard Deviation 1.01 |
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 13 | 2.78 Units on a scale | Standard Deviation 1.07 |
| Brexpiprazole 2 mg/Day + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 14 | 2.77 Units on a scale | Standard Deviation 1.14 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 13 | 3.18 Units on a scale | Standard Deviation 1.06 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 9 | 3.67 Units on a scale | Standard Deviation 0.7 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 12 | 3.23 Units on a scale | Standard Deviation 1.05 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 10 | 3.40 Units on a scale | Standard Deviation 0.82 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 14 | 3.17 Units on a scale | Standard Deviation 1.1 |
| Double-blind Placebo + ADT | Mean CGI-I Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample Per the Final Protocol. | Week 11 | 3.25 Units on a scale | Standard Deviation 0.89 |
Comparison: Statistical analysis for Week 9p-value: 0.00195% CI: [-0.4, -0.1]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 10p-value: 0.02995% CI: [-0.37, -0.02]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 11p-value: 0.042295% CI: [-0.4, -0.01]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 12p-value: 0.000395% CI: [-0.61, -0.18]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 13p-value: 0.000295% CI: [-0.64, -0.2]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 14p-value: 0.000395% CI: [-0.65, -0.19]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol
The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in Protocol Amendment 3.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol | -1.35 Units on a scale | Standard Error 0.17 |
| Double-blind Placebo + ADT | Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol | -0.89 Units on a scale | Standard Error 0.17 |
p-value: 0.034995% CI: [-0.88, -0.03]Mixed Models Analysis
Secondary
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample.
The SDS is a self-rated instrument used to measure the effect of the patient's symptoms on work/school, social life, and family/home responsibilities. For each of the three items, scores range from 0 through 10. The number most representative of how much each area was disrupted by symptoms is marked along the line from 0 = not at all, to 10 = extremely. For the work/school item, no response was to be entered if the patient did not work or go to school for reasons unrelated to the disorder and a response therefore not being applicable. The Mean SDS Score will be calculated over the three item scores. All three item scores need to be available with the exception of the work/school item score when this item is not applicable.
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample. | -1.35 Units on a scale | Standard Error 0.17 |
| Double-blind Placebo + ADT | Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample. | -0.91 Units on a scale | Standard Error 0.17 |
p-value: 0.037295% CI: [-0.86, -0.03]Mixed Models Analysis
Secondary
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample.
The items on CGI-I scale are: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The score of 0 (= not assessed) will be set to missing. The CGI-I is therefore a 7-point scale from 1 through 7. The CGI-I was measured in related to Baseline (Week 8).
Time frame: Week 9, 10, 11, 12, 13, and 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 9 | 3.41 Units on a scale | Standard Deviation 0.83 |
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 10 | 3.17 Units on a scale | Standard Deviation 0.89 |
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 11 | 3.03 Units on a scale | Standard Deviation 1.02 |
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 12 | 2.84 Units on a scale | Standard Deviation 0.99 |
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 13 | 2.74 Units on a scale | Standard Deviation 1.07 |
| Brexpiprazole 2 mg/Day + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 14 | 2.75 Units on a scale | Standard Deviation 1.13 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 13 | 3.13 Units on a scale | Standard Deviation 1.06 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 9 | 3.62 Units on a scale | Standard Deviation 0.74 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 12 | 3.19 Units on a scale | Standard Deviation 1.04 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 10 | 3.37 Units on a scale | Standard Deviation 0.82 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 14 | 3.13 Units on a scale | Standard Deviation 1.09 |
| Double-blind Placebo + ADT | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score (End of Phase A [Week 8]) to Week 14 by Trial Week for the Efficacy Sample. | Week 11 | 3.23 Units on a scale | Standard Deviation 0.9 |
Comparison: Statistical analysis for Week 9p-value: 0.002295% CI: [-0.38, -0.08]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 10p-value: 0.011595% CI: [-0.38, -0.05]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 11p-value: 0.025595% CI: [-0.41, -0.03]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 12p-value: 0.000595% CI: [-0.57, -0.16]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 13p-value: 0.000195% CI: [-0.62, -0.2]Cochran-Mantel-Haenszel
Comparison: Statistical analysis for Week 14p-value: 0.000595% CI: [-0.6, -0.17]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.
CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 44.4 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 27.7 Percentage of participants |
p-value: 0.000395% CI: [1.23, 2.1]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.
CGI-I response was defined as a CGI-I score of 1 (very much improved) or 2 (much improved).
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 43.4 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With CGI-I Scale Response Rate at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 26.4 Percentage of participants |
p-value: 0.000295% CI: [1.27, 2.27]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.
MADRS remission was defined as \</=10 and \>/=50% reduction in MADRS total score from end of Phase A (Week 8).
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 14.4 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 8.38 Percentage of participants |
p-value: 0.058695% CI: [0.98, 2.86]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.
MADRS remission was defined as \</=10 and \>/=50% reduction in MADRS total score from end of Phase A (Week 8).
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 14.9 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 8.99 Percentage of participants |
p-value: 0.067195% CI: [0.97, 2.9]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.
The MADRS response was defined as \>/=50% reduction in MADRS total score from end of Phase A (Week 8).
Time frame: Baseline and Week 14
Population: The Efficacy Sample comprised of all participants in the Safety Sample who had an end of Phase A (i.e, Week 8) value and at least one post-randomization efficacy evaluation for MADRS total score in Phase B. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 23.5 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample. | 14.7 Percentage of participants |
p-value: 0.017695% CI: [1.09, 2.44]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol.
The MADRS response was defined as \>/=50% reduction in MADRS total score from end of Phase A (Week 8).
Time frame: Baseline and Week 14
Population: All participants in the efficacy sample who met the revised randomization criteria for incomplete response as defined in protocol amendment 3. The LOCF data set included data recorded at a Phase B visit, if no observation was recorded, data was carried forward from the previous visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 2 mg/Day + ADT | Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 23.4 Percentage of participants |
| Double-blind Placebo + ADT | Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample Per the Final Protocol. | 15.7 Percentage of participants |
p-value: 0.042995% CI: [1.01, 2.35]Cochran-Mantel-Haenszel