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CompletedNCT01360645PyxisUpdated Nov 26, 2015Results posted

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

A Phase 3 interventional study of OPC-34712 + ADT and Placebo + ADT in Depressive Disorder, Depression and Depressive Disorder, Major, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 57 sites in 5 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2015-11-26.

Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. (part of Otsuka Holdings Co., Ltd.) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
826
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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

02

Conditions studied

  • Depressive Disorder
  • Depression
  • Depressive Disorder, Major
  • Mood Disorders
  • Mental Disorders

Keywords

  • OPC-34712
  • brexpiprazole
  • Major Depressive Disorder
  • Adjunctive Treatment
03

In context

Depressive Disorder

4,847 studies on the registry are indexed under Depressive Disorder; 509 are open to participants now.

This study's enrollment of 826 is above the median of 80 across 3,997 interventional studies indexed under Depressive Disorder.

Browse Depressive Disorder studies →

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 293 studies on the registry; 18 are open to participants now.

Of its 105 completed or terminated interventional studies of FDA-regulated products, 70 (67%) have results posted.

Browse Otsuka Pharmaceutical Development & Commercialization, Inc. studies →All Otsuka Holdings Co., Ltd. studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
826 participants (actual)

Study arms

  • Experimental
    Phase B

    Drug: OPC-34712 + ADT Drug: Placebo + ADT

    Drug: OPC-34712 + ADT · Drug: Placebo + ADT

  • Placebo comparator
    Phase A

    Intervention: Drug: Placebo + ADT

    Drug: Placebo + ADT

Interventions

  • DrugOPC-34712 + ADT

    Drug page: Brexpiprazole

    Tablet, Oral, 2 mg OPC-34712 and FDA Approved Antidepressant Therapy (ADT)

  • DrugPlacebo + ADT

    Placebo + FDA Approved Antidepressant (ADT)

  • DrugPlacebo + ADT

    Placebo + FDA Approved Antidepressant (ADT)

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

07

Results

Posted Nov 26, 2015

Participant flow

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

Placebo+ADT Prospective Phase-A(8 Weeks)
Participant flow — Placebo+ADT Prospective Phase-A(8 Weeks)
MilestoneSingle-blind Placebo + ADTBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADTPhase A+ Placebo + ADT
Started824000
Completed710000
Not completed114000
Withdrew: Lost to follow-up16000
Withdrew: Adverse event19000
Withdrew: Met withdrawal criteria16000
Withdrew: Withdrawal by subject34000
Withdrew: Protocol deviation24000
Withdrew: Physician decision5000
Phase B (6 Weeks)
Participant flow — Phase B (6 Weeks)
MilestoneSingle-blind Placebo + ADTBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADTPhase A+ Placebo + ADT
Started01881910
Completed01741780
Not completed014130
Withdrew: Lost to follow-up0100
Withdrew: Adverse event0600
Withdrew: Met withdrawal criteria0320
Withdrew: Withdrawal by subject0380
Withdrew: Protocol deviation0130
Phase A+
Participant flow — Phase A+
MilestoneSingle-blind Placebo + ADTBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADTPhase A+ Placebo + ADT
Started000331
Completed000307
Not completed00024
Withdrew: Lost to follow-up0007
Withdrew: Adverse event0002
Withdrew: Met withdrawal criteria0004
Withdrew: Physician decision0002
Withdrew: Withdrawal by subject0005
Withdrew: Protocol deviation0004

Outcome measures

PrimaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-8.27 ± 0.61-5.15 ± 0.60
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0001 · Mean difference (final values): -3.12 · 95% CI -4.70 to -1.54MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
PrimaryChange 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
Reported as:
Least squares mean · Units on a scale
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score for the Efficacy Sample Per the Final Protocol.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-8.36 ± 0.64-5.15 ± 0.63
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0002 · Mean difference (final values): -3.21 · 95% CI -4.87 to -1.54MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryMean 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
Reported as:
Least squares mean · Units on a scale
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in Sheehan Disability Scale (SDS) Score for the Efficacy Sample.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-1.35 ± 0.17-0.91 ± 0.17
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0372 · Mean difference (final values): -0.45 · 95% CI -0.86 to -0.03MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryMean 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
Reported as:
Least squares mean · Units on a scale
Mean Change From Baseline (End of Phase A [Week 8]) to Week 14 in SDS Score for the Efficacy Sample Per the Final Protocol
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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-1.35 ± 0.17-0.89 ± 0.17
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0349 · Mean difference (final values): -0.46 · 95% CI -0.88 to -0.03MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
Change From Baseline (End of Phase A [Week 8]) to Week 14 in MADRS Total Score by Trial Week for the Efficacy Sample.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-3.15 ± 0.40-1.86 ± 0.39
Week 10-5.15 ± 0.47-3.43 ± 0.47
Week 11-6.69 ± 0.52-4.06 ± 0.52
Week 12-7.22 ± 0.55-4.63 ± 0.54
Week 13-8.28 ± 0.58-5.10 ± 0.57
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0080 · Mean difference (final values): -1.29 · 95% CI -2.25 to -0.34MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0045 · Mean difference (final values): -1.72 · 95% CI -2.91 to -0.54MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0001 · Mean difference (final values): -2.63 · 95% CI -3.96 to -1.30MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0004 · Mean difference (final values): -2.59 · 95% CI -4.01 to -1.18MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0000 · Mean difference (final values): -3.19 · 95% CI -4.68 to -1.70MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-3.05 ± 0.41-1.74 ± 0.41
Week 10-5.04 ± 0.49-3.52 ± 0.48
Week 11-6.58 ± 0.54-4.17 ± 0.53
Week 12-7.24 ± 0.58-4.72 ± 0.57
Week 13-8.28 ± 0.61-5.01 ± 0.60
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0086 · Mean difference (final values): -1.31 · 95% CI -2.28 to -0.34MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0149 · Mean difference (final values): -1.52 · 95% CI -2.74 to -0.30MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0006 · Mean difference (final values): -2.42 · 95% CI -3.78 to -1.05MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0009 · Mean difference (final values): -2.52 · 95% CI -4.00 to -1.04MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0000 · Mean difference (final values): -3.28 · 95% CI -4.84 to -3.28MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryMean 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
Reported as:
Mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 93.41 ± 0.833.62 ± 0.74
Week 103.17 ± 0.893.37 ± 0.82
Week 113.03 ± 1.023.23 ± 0.90
Week 122.84 ± 0.993.19 ± 1.04
Week 132.74 ± 1.073.13 ± 1.06
Week 142.75 ± 1.133.13 ± 1.09
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0022 · Mean difference (final values): -0.23 · 95% CI -0.38 to -0.08P-value and treatment difference (CI) are derived from Cochran-Mantel-Haenszel (CMH) row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0115 · Mean difference (final values): -0.22 · 95% CI -0.38 to -0.05P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0255 · Mean difference (final values): -0.22 · 95% CI -0.41 to -0.03P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0005 · Mean difference (final values): -0.36 · 95% CI -0.57 to -0.16P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0001 · Mean difference (final values): -0.41 · 95% CI -0.62 to -0.20P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0005 · Mean difference (final values): -0.39 · 95% CI -0.60 to -0.17P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
SecondaryMean 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
Reported as:
Mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 93.44 ± 0.813.67 ± 0.70
Week 103.21 ± 0.893.40 ± 0.82
Week 113.07 ± 1.013.25 ± 0.89
Week 122.85 ± 1.013.23 ± 1.05
Week 132.78 ± 1.073.18 ± 1.06
Week 142.77 ± 1.143.17 ± 1.10
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0010 · Mean difference (final values): -0.25 · 95% CI -0.40 to -0.10P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0290 · Mean difference (final values): -0.19 · 95% CI -0.37 to -0.02P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0422 · Mean difference (final values): -0.20 · 95% CI -0.40 to -0.01P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0003 · Mean difference (final values): -0.39 · 95% CI -0.61 to -0.18P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0002 · Mean difference (final values): -0.42 · 95% CI -0.64 to -0.20P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0003 · Mean difference (final values): -0.42 · 95% CI -0.65 to -0.19P-value and treatment difference (CI) are derived from CMH row mean score differ test controlling for study center.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-0.25 ± 0.05-0.12 ± 0.05
Week 10-0.45 ± 0.05-0.31 ± 0.05
Week 11-0.61 ± 0.06-0.40 ± 0.06
Week 12-0.70 ± 0.07-0.45 ± 0.06
Week 13-0.86 ± 0.07-0.50 ± 0.07
Week 14-0.91 ± 0.07-0.58 ± 0.07
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0229 · Mean difference (final values): -0.13 · 95% CI -0.25 to -0.02MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0459 · Mean difference (final values): -0.14 · 95% CI -0.28 to -0.00MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0097 · Mean difference (final values): -0.21 · 95% CI -0.37 to -0.05MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0038 · Mean difference (final values): -0.25 · 95% CI -0.42 to -0.08MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0001 · Mean difference (final values): -0.36 · 95% CI -0.54 to -0.18MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0004 · Mean difference (final values): -0.34 · 95% CI -0.52 to -0.15MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-0.24 ± 0.05-0.09 ± 0.05
Week 10-0.43 ± 0.06-0.32 ± 0.06
Week 11-0.58 ± 0.06-0.42 ± 0.06
Week 12-0.70 ± 0.07-0.46 ± 0.07
Week 13-0.85 ± 0.07-0.50 ± 0.07
Week 14-0.91 ± 0.07-0.57 ± 0.07
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0109 · Mean difference (final values): -0.15 · 95% CI -0.27 to -0.04MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1286 · Mean difference (final values): -0.11 · 95% CI -0.25 to 0.03MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0521 · Mean difference (final values): -0.16 · 95% CI -0.32 to 0.00MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0084 · Mean difference (final values): -0.24 · 95% CI -0.42 to -0.06MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0003 · Mean difference (final values): -0.35 · 95% CI -0.54 to -0.16MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0006 · Mean difference (final values): -0.34 · 95% CI -0.53 to -0.15MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-3.02 ± 0.52-1.45 ± 0.51
Week 10-4.17 ± 0.59-2.64 ± 0.59
Week 11-5.41 ± 0.65-4.31 ± 0.64
Week 12-6.16 ± 0.68-4.69 ± 0.67
Week 13-7.00 ± 0.72-5.25 ± 0.71
Week 14-7.49 ± 0.74-5.52 ± 0.73
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0139 · Mean difference (final values): -1.57 · 95% CI -2.82 to -0.32MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0436 · Mean difference (final values): -1.53 · 95% CI -3.01 to -0.04MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1903 · Mean difference (final values): -1.10 · 95% CI -2.75 to 0.55MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0951 · Mean difference (final values): -1.47 · 95% CI -3.21 to 0.26MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0626 · Mean difference (final values): -1.75 · 95% CI -3.59 to 0.09MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0435 · Mean difference (final values): -1.96 · 95% CI -3.87 to -0.06MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Week 9-3.30 ± 0.53-1.59 ± 0.51
Week 10-4.29 ± 0.61-3.13 ± 0.60
Week 11-5.45 ± 0.67-4.73 ± 0.66
Week 12-6.32 ± 0.71-5.06 ± 0.70
Week 13-7.03 ± 0.74-5.60 ± 0.73
Week 14-7.59 ± 0.77-6.05 ± 0.75
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0069 · Mean difference (final values): -1.71 · 95% CI -2.95 to -0.47MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1322 · Mean difference (final values): -1.16 · 95% CI -2.68 to 0.35MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.4055 · Mean difference (final values): -0.72 · 95% CI -2.41 to 0.98MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1715 · Mean difference (final values): -1.26 · 95% CI -3.08 to 0.55MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1424 · Mean difference (final values): -1.42 · 95% CI -3.33 to 0.48MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.1270 · Mean difference (final values): -1.54 · 95% CI -3.52 to 0.44MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Item: Work/School: Week 11-0.70 ± 0.21-0.42 ± 0.22
Item: Work/School: Week 14-1.09 ± 0.22-0.90 ± 0.22
Item: Social life: Week 11-1.17 ± 0.17-0.67 ± 0.17
Item: Social life: Week 14-1.54 ± 0.19-1.04 ± 0.18
Item: Family life: Week 11-1.06 ± 0.18-0.43 ± 0.18
Item: Family life: Week 14-1.33 ± 0.19-0.73 ± 0.19
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.3079 · Mean difference (final values): -0.28 · 95% CI -0.81 to 0.26MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.4771 · Mean difference (final values): -0.19 · 95% CI -0.73 to 0.34MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0195 · Mean difference (final values): -0.50 · 95% CI -0.92 to -0.08MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0323 · Mean difference (final values): -0.50 · 95% CI -0.96 to -0.04MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0058 · Mean difference (final values): -0.63 · 95% CI -1.07 to -0.18MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0129 · Mean difference (final values): -0.60 · 95% CI -1.07 to -0.13MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
Change From Baseline (End of Phase A [Week 8]) in SDS Item Scores for the Efficacy Sample Per the Final Protocol.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Item: Work/School: Week 11-0.76 ± 0.22-0.58 ± 0.22
Item: Work/School: Week 14-1.11 ± 0.23-0.96 ± 0.23
Item: Social life: Week 11-1.18 ± 0.18-0.69 ± 0.18
Item: Social life: Week 14-1.57 ± 0.19-1.02 ± 0.19
Item: Family life: Week 11-0.99 ± 0.19-0.43 ± 0.18
Item: Family life: Week 14-0.43 ± 0.18-0.70 ± 0.19
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.5151 · Mean difference (final values): -0.18 · 95% CI -0.71 to 0.36MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.6080 · Mean difference (final values): -0.15 · 95% CI -0.70 to 0.41MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0267 · Mean difference (final values): -0.49 · 95% CI -0.92 to -0.06MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0224 · Mean difference (final values): -0.55 · 95% CI -1.01 to -0.08MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0146 · Mean difference (final values): -0.56 · 95% CI -1.01 to -0.11MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Mixed Models Analysis · p = 0.0113 · Mean difference (final values): -0.62 · 95% CI -1.09 to -0.14MMRM method was used with trial site; treatment group-visit; Baseline-visit interaction as an unstructured covariate.
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-5.89 ± 0.48-3.55 ± 0.47
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · ANCOVA · p = 0.0001 · Mean difference (final values): -2.34 · 95% CI -3.47 to -1.22
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-5.89 ± 0.51-3.59 ± 0.49
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · ANCOVA · p = 0.0002 · Mean difference (final values): -2.29 · 95% CI -3.47 to -1.12
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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-3.94 ± 0.43-2.77 ± 0.42
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · ANCOVA · p = 0.0219 · Mean difference (final values): -1.17 · 95% CI -2.17 to -0.17
SecondaryChange 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
Reported as:
Least squares mean · Units on a scale
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.
Units on a scaleBrexpiprazole 2 mg/Day + ADTDouble-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.-3.79 ± 0.45-2.70 ± 0.43
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · ANCOVA · p = 0.0376 · Mean difference (final values): -1.09 · 95% CI -2.13 to -0.06
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With MADRS Response at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.23.514.7
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0176 · Ratio of response rate: 1.63 · 95% CI 1.09 to 2.44CHM general association test controlling for trial site.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
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.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.23.415.7
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0429 · Ratio of response rate: 1.54 · 95% CI 1.01 to 2.35CHM general association test controlling for trial site.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
Percentage of Participants With MADRS Remission at Week 14 Relative to Baseline (End of Phase A [Week 8]) for the Efficacy Sample.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.14.48.38
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0586 · Ratio of remission rate: 1.68 · 95% CI 0.98 to 2.86CHM general association test controlling for trial site.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
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.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.14.98.99
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0671 · Ratio of remission rate: 1.67 · 95% CI 0.97 to 2.90CHM general association test controlling for trial site.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
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.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.44.427.7
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0003 · Ratio of response rate: 1.61 · 95% CI 1.23 to 2.10CHM general association test controlling for trial site.
SecondaryPercentage 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
Reported as:
Number · Percentage of participants
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.
Percentage of participantsBrexpiprazole 2 mg/Day + ADTDouble-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.43.426.4
Statistical analysis
  • Brexpiprazole 2 mg/Day + ADT vs Double-blind Placebo + ADT · Cochran-Mantel-Haenszel · p = 0.0002 · Ratio of response rate: 1.69 · 95% CI 1.27 to 2.27CHM general association test controlling for trial site.

Adverse events

Collected over Adverse Events with an onset date on or after the start of double-blind treatment and occurring up to 30 days after the last day of double-blind treatment were included.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Brexpiprazole 2 mg/Day + ADT—2/188 (1.1%)37/188 (19.7%)
Double-blind Placebo + ADT—2/191 (1%)27/191 (14.1%)
Most frequent serious events
Most frequent serious events
EventBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Abdominal PainGastrointestinal disorders1/1880/191
Comminuted FractureInjury, poisoning and procedural complications1/1880/191
SyncopeNervous system disorders1/1880/191
Atrial FibrillationCardiac disorders0/1881/191
PneumoniaInfections and infestations0/1881/191
Most frequent other events
Most frequent other events
EventBrexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADT
Weight increasedInvestigations15/1886/191
AkathisiaNervous system disorders14/1882/191
Upper resporatory tract infectionInfections and infestations6/18812/191
DiarrhoeaGastrointestinal disorders5/18810/191

Baseline characteristics

Randomized sample were used. Randomized sample comprises all who were randomized in Phase B.

Age, Continuous
Age, Continuous(Years)Brexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADTTotal
Mean44.1 ± 11.645.2 ± 11.344.6 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)Brexpiprazole 2 mg/Day + ADTDouble-blind Placebo + ADTTotal
Female130137267
Male5854112
08

Study locations

57 sites
  • Research Site
    Arcadia, California, United States
  • Research Site
    Beverly Hills, California, United States
  • Research Site
    Fresno, California, United States
  • Research Site
    Oceanside, California, United States
  • Research Site
    San Diego, California, United States
  • Research Site
    San Francisco, California, United States
  • Research Site
    Sherman Oaks, California, United States
  • Research Site
    Denver, Colorado, United States
  • Research Site
    Norwalk, Connecticut, United States
  • Research Site
    Coral Springs, Florida, United States
  • Research Site
    Fort Myers, Florida, United States
  • Research Site
    Hialeah, Florida, United States
  • Research Site
    Jacksonville, Florida, United States
  • Research Site
    Melbourne, Florida, United States
  • Research Site
    Orlando, Florida, United States
  • Research Site
    Indianapolis, Indiana, United States
  • Research Site
    Prairie Village, Kansas, United States
  • Research Site
    Wichita, Kansas, United States
  • Research Site
    New Orleans, Louisiana, United States
  • Research Site
    Shreveport, Louisiana, United States
  • Research Site
    Belmont, Massachusetts, United States
  • Research Site
    Boston, Massachusetts, United States
  • Research Site
    Lincoln, Nebraska, United States
  • Research Site
    New York, New York, United States
  • Research Site
    Rochester, New York, United States
  • Research Site
    Dayton, Ohio, United States
  • Research Site
    Toledo, Ohio, United States
  • Research Site
    Salem, Oregon, United States
  • Research Site
    Allentown, Pennsylvania, United States
  • Research Site
    Bala-Cynwyd, Pennsylvania, United States
  • Research Site
    Bridgeville, Pennsylvania, United States
  • Research Site
    Philadelphia, Pennsylvania, United States
  • Research Site
    San Antonio, Texas, United States
  • Research Site
    Murray, Utah, United States
  • Research Site
    Woodstock, Vermont, United States
  • Research Site
    Richmond, Virginia, United States
  • Research Site
    Seattle, Washington, United States
  • Research Site
    Penticton, British Columbia, Canada
  • Research Site
    Toronto, Ontario, Canada
  • Research Site
    Gatineau, Quebec, Canada
  • Research Site
    Arcachon, France
  • Research Site
    Élancourt, France
  • Research Site
    Orvault, France
  • Research Site
    Palaiseau, France
  • Research Site
    Toulouse, France
  • Research Site
    Bełchatów, Poland, Poland
  • Research Site
    Katowice, Upper Silesia, Poland
  • Research Site
    Poznan, Woj. Wielkopolskie, Poland
  • Research Site
    Gdynia, Poland
  • Research Site
    Kielce, Poland
  • Research Site
    Lublin, Poland
  • Research Site
    Tuszyn, Poland
  • Research Site
    Warsaw, Poland
  • Research Site
    Kosice-Barca, Slovakia, Slovakia
  • Research Site
    Bratislava, Slovakia
  • Research Site
    Levice, Slovakia
  • Research Site
    Michalovce, Slovakia
09

References and documents

Publications

  • Kapadia S, Zhang Z, Ardic F, Patel M, Thase ME, Papakostas GI. Adjunctive brexpiprazole in patients with major depressive disorder who show minimal or partial response to antidepressant treatment: post hoc analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2025 Oct 1;28(10):pyaf074. doi: 10.1093/ijnp/pyaf074. PubMed 41055581 ↗
  • Ardic F, Zhang Z, Hogan M. Effects of adjunctive brexpiprazole in patients with major depressive disorder and sleep disturbance: a post hoc analysis of three randomized trials. Front Psychiatry. 2025 Aug 7;16:1618176. doi: 10.3389/fpsyt.2025.1618176. eCollection 2025. PubMed 40852147 ↗
  • Kapadia S, Zhang Z, Csoboth C, Patel M, Thase ME, Papakostas GI. Adjunctive brexpiprazole in patients with unresolved symptoms of depression on antidepressant treatment who are early in the disease course: post hoc analysis of randomized controlled trials. Int J Neuropsychopharmacol. 2025 Aug 1;28(8):pyaf050. doi: 10.1093/ijnp/pyaf050. PubMed 40607746 ↗
  • McIntyre RS, Bubolic S, Zhang Z, MacKenzie EM, Therrien F, Miguelez M, Boucher M. Effects of Adjunctive Brexpiprazole on Individual Depressive Symptoms and Functioning in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of Three Placebo-Controlled Studies. J Clin Psychopharmacol. 2024 Mar-Apr 01;44(2):133-140. doi: 10.1097/JCP.0000000000001825. PubMed 38421922 ↗
  • Newcomer JW, Meehan SR, Chen D, Brubaker M, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies. J Clin Psychiatry. 2023 Aug 28;84(5):23m14786. doi: 10.4088/JCP.23m14786. PubMed 37656180 ↗
  • McIntyre RS, Therrien F, Ismail Z, Meehan SR, Miguelez M, Larsen KG, Chen D, MacKenzie EM, Thase ME. Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data. J Psychiatr Res. 2023 Jun;162:71-78. doi: 10.1016/j.jpsychires.2023.04.012. Epub 2023 Apr 12. PubMed 37099968 ↗
  • Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1;80(6):18m12680. doi: 10.4088/JCP.18m12680. PubMed 31577867 ↗
  • Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H. Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale. Int J Neuropsychopharmacol. 2019 Mar 1;22(3):173-179. doi: 10.1093/ijnp/pyy095. PubMed 30508090 ↗
  • McIntyre RS, Weiller E, Zhang P, Weiss C. Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials. J Affect Disord. 2016 Sep 1;201:116-23. doi: 10.1016/j.jad.2016.05.013. Epub 2016 May 12. PubMed 27208498 ↗
  • Thase ME, Youakim JM, Skuban A, Hobart M, Augustine C, Zhang P, McQuade RD, Carson WH, Nyilas M, Sanchez R, Eriksson H. Efficacy and safety of adjunctive brexpiprazole 2 mg in major depressive disorder: a phase 3, randomized, placebo-controlled study in patients with inadequate response to antidepressants. J Clin Psychiatry. 2015 Sep;76(9):1224-31. doi: 10.4088/JCP.14m09688. PubMed 26301701 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 26, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01360645
Lead sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Responsible party
Sponsor
First posted
May 25, 2011
Start date
Jul 2011
Primary completion
May 2013
Completion
Jun 2013
Results posted
Nov 26, 2015
Last update
Nov 26, 2015

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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