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Trial record 36 of 64 for:    brexpiprazole

A Study of Flexible-dose Brexpiprazole as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial

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ClinicalTrials.gov Identifier: NCT01727726
Recruitment Status : Completed
First Posted : November 16, 2012
Results First Posted : June 8, 2018
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Interventions Drug: Brexpiprazole
Drug: Seroquel XR
Drug: Placebo
Enrollment 2182
Recruitment Details Trial was conducted at 75 trial sites in 7 countries (United States, Russia, Poland, France, Serbia,Germany & Canada). Phase A non-responders entered Phase B (503 subjects randomized in 2:2:1 (197+100+206) ratio - brexpiprazole/Seroquel extended release tablets/placebo +ADT).
Pre-assignment Details Screening period ranged from a minimum of 7 days to a maximum of 28 days and began when informed consent was signed. The purpose of the screening period was to assess eligibility criteria at 1 or more visits (as necessary to complete screening assessments) and to washout (minimum of 24 hours) prohibited concomitant pharmacotherapy, if applicable.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule at 1 mg, 2 mg, 3 mg.

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule at 50 mg, 150 mg, 300 mg.

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Period Title: Overall Study
Started 197 100 206
Completed 171 86 186
Not Completed 26 14 20
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT Total
Hide Arm/Group Description

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Total of all reporting groups
Overall Number of Baseline Participants 197 100 206 503
Hide Baseline Analysis Population Description
Randomized sample comprised all subjects who were randomized in Phase B. Subjects were considered randomized when they were assigned a treatment number by IVRS at the end of Phase A. A subject receiving IMP outside of the IVRS was not considered randomized, but safety was reported.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 100 participants 206 participants 503 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
197
 100.0%
100
 100.0%
206
 100.0%
503
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 197 participants 100 participants 206 participants 503 participants
43.6  (11.5) 44.6  (11.6) 41.8  (11.7) 43  (11.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 197 participants 100 participants 206 participants 503 participants
Female
128
  65.0%
66
  66.0%
149
  72.3%
343
  68.2%
Male
69
  35.0%
34
  34.0%
57
  27.7%
160
  31.8%
1.Primary Outcome
Title Montgomery Asberg Depression Rating Scale (MADRS)
Hide Description To determine the efficacy of brexpiprazole (flexible dose) with placebo as adjunctive therapy by assessment of MADRS total score. The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Time Frame Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-6.04  (0.43) -4.86  (0.57) -4.57  (0.41)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.48
Confidence Interval (2-Sided) 95%
-2.56 to -0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6642
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-1.63 to 1.04
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Sheehan Disability Scale (SDS)
Hide Description To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale is a measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains ( work/social life/family life/home responsibilities). 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. Scores of 5 and above are associated with significant functional impairment. Additionally, SDS included 2 questions related to productivity losses due to the psychiatric symptoms and impairment.
Time Frame Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for SDS Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.97  (0.12) -0.32  (0.16) -0.74  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1334
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.52 to 0.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0237
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.06 to 0.78
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From End of Phase A in MADRS Total Score for Trial Week 2 and Week 4.
Hide Description Change from end of Phase A in MADRS Total Score. The MADRS was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS depression rating scale was used to assess the subject's level of depression by utilizing the structured interview guide for the MADRS (SIGMA). The MADRS consisted of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts and suicidal thoughts), each rated 0 to 6. The overall score ranged from 0 (symptoms absent) to 60 (severe depression). Lower score indicated decreased severity of depression.
Time Frame Change from baseline to week 2 and week 4 in Phase B (week 10/12 and week 12/14)
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Phase B Week 2 Number Analyzed 188 participants 99 participants 203 participants
-2.57  (0.32) -2.26  (0.41) -1.04  (0.31)
Phase B Week 4 Number Analyzed 178 participants 94 participants 192 participants
-4.39  (0.39) -3.30  (0.51) -3.22  (0.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Phase B week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.53
Confidence Interval (2-Sided) 95%
-2.29 to -0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Phase B Week 2
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0103
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-2.15 to -0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Phase B week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0185
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-2.15 to -0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Phase B Week 4
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8949
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-1.27 to 1.11
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Global Impression Score
Hide Description Mean change from end of Phase A in Clinical Global Impression - Severity of Illness scale (CGI-S) score and Improvement scale (CGI-I) during double-blind randomized Phase B treatment. CGI-S score assessed how mentally ill the patient was at that time. CGI-S score is calculated from 0 to 7 (0 indicates not assessed 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and7 indicated among the most extremely ill patient). CGI-I score is compared to his/her condition at baseline, how much has the patient changed. CGI-I score is calculated from 0 to 7 (0 indicates not assessed and 7 indicates very much worse).
Time Frame From randomization to Phase B week 6 (14/16 weeks after randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for CGI-S score and CGI-I score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Mean (Standard Deviation)
Unit of Measure: Mean score
CGI-Severity of Illness Scale 3.98  (0.56) 4.07  (0.58) 4.02  (0.58)
CGI-Improvement Scale Score 2.55  (0.84) 2.71  (0.87) 2.74  (0.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments CGI-Severity of Illness Scale Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0350
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.29 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments CGI-Severity of Illness Scale Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5601
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.22 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments CGI-Improvement Scale Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0146
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.35 to -0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments CGI-Improvement Scale Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7127
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.23 to 0.15
Estimation Comments [Not Specified]
5.Secondary Outcome
Title MADRS Response at Week 6
Hide Description MADRS Response Rate, where response was defined as 50% reduction in MADRS Total Score, during double-blind randomized Phase B treatment.
Time Frame Phase B week 6 (14/16 weeks after randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Measure Type: Count of Participants
Unit of Measure: Participants
20
  10.5%
8
   8.1%
14
   6.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2242
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of response rate
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
0.78 to 2.84
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5998
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.53 to 2.98
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With MADRS
Hide Description MADRS Remission Rate, where remission was defined as MADRS Total Score ≤ 10 and 50% reduction in MADRS Total Score, for every trial week visit during double-blind randomized Phase B treatment.
Time Frame Phase B week 6 (14/16 weeks after randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
Number of subjects in the Safety Sample who had an end of Phase A (ie, Week 8 or 10) value and at least one post randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Measure Type: Count of Participants
Unit of Measure: Participants
13
   6.8%
2
   2.0%
9
   4.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3321
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
0.66 to 3.49
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3917
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.11 to 2.46
Estimation Comments [Not Specified]
7.Secondary Outcome
Title CGI-I Response Rate
Hide Description CGI-I Response rate, where response was defined as a CGI-I score of 1 or 2 (very much improved or much improved), during double-blind randomized Phase B treatment.
Time Frame Phase B week 6 (14/16 weeks after randomization).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Measure Type: Count of Participants
Unit of Measure: Participants
100
  52.4%
48
  48.5%
79
  38.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
1.10 to 1.66
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Phase B Week 6
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0898
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.98 to 1.59
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description To evaluate the safety and tolerability of brexpiprazole (flexible dose) as adjunctive therapy to ADT in the proposed subject population with MDD as AE variables.
Time Frame From screening (Day -28 to Day-1) upto post treatment follow-up.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized subjects in Phase B who received at least one dose of double-blind trial medication as indicated on the dosing record.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 197 100 206
Measure Type: Count of Participants
Unit of Measure: Participants
Death
0
   0.0%
0
   0.0%
0
   0.0%
Serious TEAE
0
   0.0%
1
   1.0%
1
   0.5%
Discontinuation due to TEAE
2
   1.0%
4
   4.0%
1
   0.5%
Any TEAE
100
  50.8%
58
  58.0%
107
  51.9%
9.Secondary Outcome
Title Sheehan Disability Scale (SDS) Individual Item Scores.
Hide Description To evaluate mean change in SDS score from randomization (End of Phase A) to end of Phase B. The Sheehan Disability Scale (a self rated questionnaire) was used for measurement of functional disability and impairment due to psychiatric symptoms. The SDS is a visual analogue scale that uses spatio-visual, numeric, and verbal descriptive anchors simultaneously to assess disability across the three domains (work/school work, social life/leisure activities and family life/home responsibilities). All domains were rated on a score scale ranged from 0 (no impairment) to 10 (most severe). Score of 5 and above indicated significant functional impairment. A total score was addition of the 3 individual scores and the total score ranged from 0 (no impairment) to 30 (most severe).
Time Frame Randomization Visit (week 8 or week 10) to End of Double-Blind Treatment (week 14 or week 16).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects in the Safety Sample who have an end of Phase A (ie, Week 8 or 10) value and at least one post-randomization efficacy evaluation for MADRS Total Score in Phase B.
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description:

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

Overall Number of Participants Analyzed 191 99 205
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Work/School Score Number Analyzed 125 participants 67 participants 136 participants
-0.59  (0.16) -0.22  (0.21) -0.74  (0.16)
Social Life Score Number Analyzed 191 participants 99 participants 205 participants
-1.03  (0.13) -0.26  (0.17) -0.70  (0.12)
Family Life Score Number Analyzed 191 participants 99 participants 205 participants
-1.02  (0.13) -0.34  (0.18) -0.67  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Work/School Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4480
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.25 to 0.56
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Work/School Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0380
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.03 to 1.02
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Social Life Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0436
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.66 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Social Life Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0350
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.03 to 0.84
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole + ADT, Seroquel XR + ADT
Comments Family Life Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0424
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.69 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Seroquel XR + ADT, Placebo + ADT
Comments Family Life Score
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1230
Comments [Not Specified]
Method MMRM
Comments Mixed-model repeated measures (MMRM)
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-0.09 to 0.75
Estimation Comments [Not Specified]
Time Frame Adverse events were recorded from screening (Day -28 to Day-1) upto post treatment follow-up.
Adverse Event Reporting Description All adverse events which started after start of double blind study drug treatment; or if the event was continuous from end of phase A and was worsening, serious, study drug related, or resulted in death, discontinuation, interruption or reduction of study therapy. Subjects in Phase B who received at least one dose of double-blind IMP as indicated on the dosing record. If a subject was dispensed IMP and was lost to follow up, he/she was considered exposed.
 
Arm/Group Title Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Hide Arm/Group Description

Brexpiprazole, flexible dose and assigned ADT

Brexpiprazole: tablet/capsule

Seroquel XR, flexible dose and assigned ADT

Seroquel XR: tablet/capsule

Matching Placebo and assigned ADT

Placebo: tablet/capsule

All-Cause Mortality
Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/197 (0.00%)      0/100 (0.00%)      0/206 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/197 (0.00%)      1/100 (1.00%)      1/206 (0.49%)    
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
malignanat melanoma  1  0/197 (0.00%)  0 1/100 (1.00%)  1 0/206 (0.00%)  0
Psychiatric disorders       
panic attack  1  0/197 (0.00%)  0 0/100 (0.00%)  0 1/206 (0.49%)  1
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Brexpiprazole + ADT Seroquel XR + ADT Placebo + ADT
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   62/197 (31.47%)      33/100 (33.00%)      39/206 (18.93%)    
General disorders       
Asthenia  1  4/197 (2.03%)  2/100 (2.00%)  0/206 (0.00%) 
fatigue  1  3/197 (1.52%)  4/100 (4.00%)  3/206 (1.46%) 
Infections and infestations       
Nasopharyngitis  1  9/197 (4.57%)  2/100 (2.00%)  9/206 (4.37%) 
Investigations       
Weight Increased  1  7/197 (3.55%)  4/100 (4.00%)  4/206 (1.94%) 
Metabolism and nutrition disorders       
Increased Appetite  1  5/197 (2.54%)  5/100 (5.00%)  2/206 (0.97%) 
Nervous system disorders       
Akathisia  1  12/197 (6.09%)  3/100 (3.00%)  4/206 (1.94%) 
Dizziness  1  7/197 (3.55%)  3/100 (3.00%)  5/206 (2.43%) 
Headache  1  11/197 (5.58%)  1/100 (1.00%)  10/206 (4.85%) 
Somnolence  1  11/197 (5.58%)  18/100 (18.00%)  2/206 (0.97%) 
Psychiatric disorders       
Insomnia  1  5/197 (2.54%)  3/100 (3.00%)  4/206 (1.94%) 
Irritability  1  4/197 (2.03%)  1/100 (1.00%)  3/206 (1.46%) 
Restlessness  1  5/197 (2.54%)  1/100 (1.00%)  2/206 (0.97%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Global Clinical Development
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01727726     History of Changes
Other Study ID Numbers: 331-12-282
First Submitted: October 31, 2012
First Posted: November 16, 2012
Results First Submitted: January 3, 2018
Results First Posted: June 8, 2018
Last Update Posted: June 8, 2018