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Study of the Effectiveness of Three Different Doses of OPC-34712 in the Treatment of Adults With Acute Schizophrenia (VECTOR)

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ClinicalTrials.gov Identifier: NCT01396421
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : October 29, 2015
Last Update Posted : October 29, 2015
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
Condition Acute Schizophrenia
Interventions Drug: OPC-34712 [Brexpiprazole] High Dose
Drug: Experimental: OPC-34712 [Brexpiprazole] Middle Dose
Drug: Experimental: OPC-34712 [Brexpiprazole] Low Dose
Drug: Placebo
Enrollment 636

Recruitment Details The trial was conducted in 636 participants from 65 trial sites in 10 countries.
Pre-assignment Details Adults with schizophrenia as defined by Diagnostic and Statistical Manual of Mental Health Disorders 4th Edition Text Revision criteria and confirmed by the Mini International Neuropsychiatric Interview for schizophrenia and psychotic disorders studies.
Arm/Group Title Brexpiprazole 4 mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description

Brexpiprazole 4 milligram (mg) tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
Period Title: Overall Study
Started 180 182 90 184
Completed 121 124 56 109
Not Completed 59 58 34 75
Reason Not Completed
Lost to Follow-up             0             0             0             1
Adverse Event             17             15             12             32
Participant Met Withdrawal Criteria             1             0             1             0
Physician Decision             1             1             0             3
Withdrawal by Subject             31             24             13             21
Protocol Deviation             2             1             1             0
Lack of Efficacy             7             17             7             18
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25 mg Placebo Total
Hide Arm/Group Description

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 180 182 90 184 636
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 180 participants 182 participants 90 participants 184 participants 636 participants
40.8  (11.0) 39.6  (10.2) 40.5  (11.4) 39.7  (10.8) 40.1  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 180 participants 182 participants 90 participants 184 participants 636 participants
Female
69
  38.3%
71
  39.0%
29
  32.2%
66
  35.9%
235
  36.9%
Male
111
  61.7%
111
  61.0%
61
  67.8%
118
  64.1%
401
  63.1%
1.Primary Outcome
Title Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score.
Hide Description The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 134, 132, 62 and 124 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2 mg Brexpiprazole 0.25 mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 134 132 62 124
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-19.65  (1.54) -20.73  (1.55) -14.90  (2.23) -12.01  (1.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Brexpiprazole 2 mg, Placebo
Comments Difference between average effect of brexpiprazole 2 and 4 mg/day and placebo was tested first at alpha level of 0.05. If statistically significant, then comparisons for each group (brexpiprazole 2 and 4 mg/day) versus placebo were performed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Primary analysis was performed by fitting a Mixed Model Repeated Measures (MMRM) which included fixed class effect terms for treatment, trial site, visit week, and an interaction term of treatment by visit week.
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -8.18
Confidence Interval (2-Sided) 95%
-12.0 to -4.40
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of −7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -7.64
Confidence Interval (2-Sided) 95%
-12.0 to -3.30
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of −7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Traetment difference
Estimated Value -8.72
Confidence Interval (2-Sided) 95%
-13.1 to -4.37
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25 mg, Placebo
Comments Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of −7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-test
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2910
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.89
Confidence Interval (2-Sided) 95%
-8.27 to 2.49
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
Hide Description The severity of illness was rated using the CGI-S which is the key secondary endpoint. To perform this assessment, the rater or study physician answered the following question: “Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?” Response choices included: 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; and 7=among the most extremely ill participant.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 124, 56 and 109 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4 mg Brexpiprazole 2 mg Brexpiprazole 0.25 mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 124 56 109
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-1.20  (0.08) -1.15  (0.08) -0.85  (0.12) -0.82  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Brexpiprazole 2 mg, Placebo
Comments Difference between the average effect of brexpiprazole 2 and 4 mg/day and placebo was tested first at alpha level of 0.05. If statistically significant, then comparisons for each group (brexpiprazole 2 and 4 mg/day) versus placebo were performed at a significance level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.56 to -0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.61 to -0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.56 to -0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8491
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM with fixed effect of treatment, clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.31 to 0.26
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score.
Hide Description The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame Baseline to Week 1, 2, 3, 4, 5
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1),and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5).

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 178 180 87 178
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -4.38  (0.60) -4.87  (0.59) -2.52  (0.83) -2.87  (0.60)
Week 2 -9.51  (0.93) -8.86  (0.93) -3.28  (1.32) -5.11  (0.95)
Week 3 -12.78  (1.15) -11.08  (1.16) -5.71  (1.65) -7.64  (1.18)
Week 4 -16.50  (1.32) -14.06  (1.32) -8.86  (1.90) -8.89  (1.35)
Week 5 -18.61  (1.42) -17.90  (1.43) -11.87  (2.05) -10.75  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0644
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, and baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-3.09 to 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0139
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.99
Confidence Interval (2-Sided) 95%
-3.58 to -0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7231
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-1.61 to 2.32
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0018
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -5.14
Confidence Interval (2-Sided) 95%
-8.36 to -1.93
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates
Method Mixed Models Analysis
Comments Week 2
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.75
Confidence Interval (2-Sided) 95%
-6.33 to -1.17
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2568
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 2
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.84
Confidence Interval (2-Sided) 95%
-1.34 to 5.02
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 2
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -4.40
Confidence Interval (2-Sided) 95%
-6.97 to -1.82
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0360
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -3.45
Confidence Interval (2-Sided) 95%
-6.67 to -0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9876
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-4.53 to 4.60
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -7.61
Confidence Interval (2-Sided) 95%
-11.3 to -3.93
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -5.16
Confidence Interval (2-Sided) 95%
-8.85 to -1.47
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3407
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.93
Confidence Interval (2-Sided) 95%
-2.05 to 5.90
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -7.86
Confidence Interval (2-Sided) 95%
-11.9 to -3.86
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -7.15
Confidence Interval (2-Sided) 95%
-11.2 to -3.14
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6570
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.12
Confidence Interval (2-Sided) 95%
-6.07 to 3.83
Estimation Comments Because only the comparison of brexpiprazole 4 mg/day versus placebo met the threshold in the primary analysis, the following analysis is not part for the formal statistical testing and is descriptive only.
4.Secondary Outcome
Title Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
Hide Description The severity of illness was rated using the CGI-S. To perform this assessment, the rater or study physician answered the following question: “Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?” Response choices included: 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; and 7=among the most extremely ill participant.
Time Frame Baseline to Week 1, 2, 3, 4 and 5
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 178 181 89 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.16  (0.04) -0.16  (0.04) -0.11  (0.05) -0.14  (0.04)
Week 2 -0.46  (0.05) -0.43  (0.05) -0.18  (0.07) -0.30  (0.05)
Week 3 -0.72  (0.06) -0.60  (0.06) -0.33  (0.09) -0.51  (0.07)
Week 4 -0.96  (0.07) -0.73  (0.07) -0.58  (0.11) -0.54  (0.08)
Week 5 -1.08  (0.08) -1.03  (0.08) -0.73  (0.11) -0.69  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6553
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.13 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6170
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.13 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6446
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates..
Method Mixed Models Analysis
Comments Week 1
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.10 to 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 2
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.29 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0825
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Leasr squares mean
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.27 to 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1678
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 2
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-0.05 to 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0219
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.39 to -0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3275
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.27 to 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1173
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 3
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.04 to 0.40
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.63 to -0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0662
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.40 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7587
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 4
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.30 to 0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.61 to -0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.56 to -0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7619
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 5
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.32 to 0.23
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)
Hide Description The PSP is a clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment in each of these domains was rated as absent, mild, manifest, marked, severe, or very severe. These ratings were then converted to a total score based on a 100-point scale using algorithms to identify the appropriate 10-point interval, and the rater’s judgment to determine the total score within the 10-point interval. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented manifest disabilities of various degrees and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 122, 55 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a r5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 122 55 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
12.72  (0.93) 13.15  (0.93) 11.84  (1.33) 10.26  (0.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0557
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 6
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.46
Confidence Interval (2-Sided) 95%
-0.06 to 4.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0250
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 6
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 2.89
Confidence Interval (2-Sided) 95%
0.37 to 5.42
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3264
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments Week 6
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
-1.58 to 4.74
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score
Hide Description For each symptom construct of the PANSS Positive Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-6.78  (0.51) -6.57  (0.52) -5.46  (0.74) -4.35  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.44
Confidence Interval (2-Sided) 95%
-3.88 to -0.99
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.22
Confidence Interval (2-Sided) 95%
-3.67 to -0.77
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2227
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.11
Confidence Interval (2-Sided) 95%
-2.90 to 0.68
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score
Hide Description For each symptom construct of the PANSS Negative Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.65  (0.36) -4.02  (0.36) -3.31  (0.53) -2.24  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.41
Confidence Interval (2-Sided) 95%
-2.44 to 0.39
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean
Estimated Value -1.78
Confidence Interval (2-Sided) 95%
-2.81 to -0.76
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0996
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatmetn difference
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-2.33 to 0.20
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6
Hide Description The participant’s overall improvement was rated using the CGI-I. The rater or study physician rated the participant’s total improvement whether or not it was due entirely to drug treatment. All responses were compared with the participant’s condition at screening/baseline. Response choices were: 0=not assessed, 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, and 7=very much worse.
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 178 181 89 178
Mean (Standard Deviation)
Unit of Measure: Units on a scale
2.94  (1.29) 2.94  (1.34) 3.37  (1.46) 3.48  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments The Cochran-Mantel-Haenzel (CMH) row mean scores differ test controlling for trial center was applied to CGI-I score.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.77 to -0.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The CMH row mean scores differ test controlling for trial center was applied to CGI-I score.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.82 to -0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4505
Comments The CMH row mean scores differ test controlling for trial center was applied to CGI-I score.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.50 to 0.22
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Response Rate at Week 6
Hide Description Response rate was defined as improvement in mean change of ≥30% from baseline in PANSS Total Score at Week 6 or CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6.
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 178 180 87 178
Measure Type: Number
Unit of Measure: Percentage of participants
46.07 47.78 39.08 30.34
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments CMH general association test controlling for trial was applied to the analysis of response rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 1.48
Confidence Interval (2-Sided) 95%
1.14 to 1.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments CMH general association test controlling for trial was applied to the analysis of response rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
1.23 to 2.05
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1576
Comments CMH general association test controlling for trial was applied to the analysis of response rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.92 to 1.76
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score
Hide Description The PEC consists of 5 PANSS items (excitement [P4], hostility [P7], tension [G4], uncooperativeness [G8], and poor impulse control [G14]). Each rated on a scale of 1 (absent) to 7 (extreme). The PEC for participants was calculated as the sum of the rating assigned to each of the 5 items, and ranged from 5 to 35 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-2.75  (0.34) -2.87  (0.34) -1.99  (0.49) -1.64  (0.36)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0246
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.10
Confidence Interval (2-Sided) 95%
-2.06 to -0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0131
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-2.19 to -0.26
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5706
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-1.53 to 0.85
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Discontinuation Rate for Lack of Efficacy at Week 6
Hide Description [Not Specified]
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 178 180 87 178
Measure Type: Number
Unit of Measure: Percentage of participants
3.93 9.44 8.05 10.11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0143
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test controlling for trial center was applied to the analysis of discontinuation rate.
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.18 to 0.85
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6606
Comments CMH general association test controlling for trial center was applied to the analysis of discontinuation rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.46 to 1.65
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5115
Comments CMH general association test controlling for trial center was applied to the analysis of discontinuation rate.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative risk
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.35 to 1.68
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score
Hide Description The PANSS Marder Factor score - Positive Symptoms Score consists of 8 PANSS items (delusions [P1], hallucinatory behaviour [P3], grandiosity [P5], suspiciousness [P6], stereotyped thinking [N7], somatic concern [G1], unusual thought content [G9], lack of judgment and insight [G10]. Each was rated on a scale of 1 (absent) to 7 (extreme). The PANSS Marder Factor score - Positive Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 8 items, and ranged from 8 to 42 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-7.23  (0.51) -7.37  (0.51) -5.78  (0.73) -4.89  (0.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-3.77 to -0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -2.47
Confidence Interval (2-Sided) 95%
-3.91 to -1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3263
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.89
Confidence Interval (2-Sided) 95%
-2.66 to 0.89
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score
Hide Description The PANSS Marder Factor score - Negative Symptoms Score consists of 7 PANSS items (blunted effect [N1], emotional withdrawal [N2], poor rapport [N3], passive/apathetic social withdrawal [N4], lack of spontaneity and conversation flow [N6], motor retardation [G7], active social avoidance [G16]). The PANSS Marder Factor score - Negative Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-4.10  (0.37) -4.48  (0.37) -3.66  (0.54) -2.80  (0.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0155
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-2.35 to -0.25
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.68
Confidence Interval (2-Sided) 95%
-2.73 to -0.62
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1956
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.86
Confidence Interval (2-Sided) 95%
-2.17 to 0.44
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score
Hide Description The PANSS Marder Factor score -Disorganized Thought Score consists of 7 PANSS items (conceptual disorganization [P2], difficulty in abstract thinking [N5], mannerisms and posturing [G5], disorientation [G10], poor attention [G11], disturbance of violation [G13], preoccupation [G15]). The PANSS Marder Factor score - Disorganized Thought Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.72  (0.36) -3.94  (0.36) -2.69  (0.52) -1.97  (0.37)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-2.76 to -0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.98
Confidence Interval (2-Sided) 95%
-2.98 to -0.97
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2572
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-1.96 to 0.52
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score
Hide Description The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score consists of 4 PANSS items (excitement [P4], hostility [P7], uncooperativeness [G8], poor impulse control [G14]). The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of placebo over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of placebo over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-1.90  (0.28) -1.91  (0.28) -1.15  (0.41) -0.82  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0085
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-1.87 to -0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0081
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-1.88 to -0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5172
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-1.31 to 0.66
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score
Hide Description The PANSS Marder Factor score - Anxiety/Depression Score consists of 4 PANSS items (anxiety [G2], guilt feelings [G3], tension [G4], depression [G6]). The PANSS Marder Factor score - Anxiety/Depression Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Time Frame Baseline to Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2mg Brexpiprazole 0.25mg Placebo
Hide Arm/Group Description:

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 121 123 56 108
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.40  (0.25) -3.70  (0.25) -3.27  (0.35) -3.05  (0.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3284
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-1.03 to 0.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0655
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-1.34 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 0.25mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6251
Comments MMRM with fixed effect of treatment, (pooled) clinical center, visit, treatment visit interaction, baseline value, baseline visit interaction as covariates.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-1.07 to 0.64
Estimation Comments [Not Specified]
Time Frame Adverse events were recorded from the time the participant signs the informed consent form, throughout the 6-week treatment period and until 30 days after the last dose of study medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Brexpiprazole 4mg Brexpiprazole 2 mg Brexpiprazile 0.25 mg Placebo
Hide Arm/Group Description

Brexpiprazole 4mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2).

Brexpiprazole 2mg tablet once daily for 6 weeks.

Participants were titrated to the target dose of brexpiprazole over a 5-day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5.

Brexpiprazole 0.25mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
All-Cause Mortality
Brexpiprazole 4mg Brexpiprazole 2 mg Brexpiprazile 0.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole 4mg Brexpiprazole 2 mg Brexpiprazile 0.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/180 (1.11%)   4/182 (2.20%)   4/90 (4.44%)   7/184 (3.80%) 
Cardiac disorders         
Acute myocardial infarction * 1  0/180 (0.00%)  0/182 (0.00%)  1/90 (1.11%)  0/184 (0.00%) 
Gastrointestinal disorders         
Gastric ulcer * 1  0/180 (0.00%)  0/182 (0.00%)  0/90 (0.00%)  1/184 (0.54%) 
Musculoskeletal and connective tissue disorders         
Rhabdomyolysis * 1  0/180 (0.00%)  1/182 (0.55%)  0/90 (0.00%)  0/184 (0.00%) 
Nervous system disorders         
Grand mal convulsion * 1  0/180 (0.00%)  0/182 (0.00%)  0/90 (0.00%)  1/184 (0.54%) 
Psychiatric disorders         
Psychotic disorder * 1  0/180 (0.00%)  1/182 (0.55%)  1/90 (1.11%)  2/184 (1.09%) 
Schizophrenia * 1  2/180 (1.11%)  2/182 (1.10%)  2/90 (2.22%)  2/184 (1.09%) 
Schizophrenia, paranoid type * 1  0/180 (0.00%)  0/182 (0.00%)  0/90 (0.00%)  1/184 (0.54%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 16
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole 4mg Brexpiprazole 2 mg Brexpiprazile 0.25 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   64/180 (35.56%)   53/182 (29.12%)   25/90 (27.78%)   65/184 (35.33%) 
Gastrointestinal disorders         
Diarrhoea * 1  7/180 (3.89%)  3/182 (1.65%)  5/90 (5.56%)  3/184 (1.63%) 
Nausea * 1  6/180 (3.33%)  10/182 (5.49%)  1/90 (1.11%)  8/184 (4.35%) 
Nervous system disorders         
Akathisia * 1  13/180 (7.22%)  8/182 (4.40%)  0/90 (0.00%)  4/184 (2.17%) 
Headache * 1  22/180 (12.22%)  17/182 (9.34%)  9/90 (10.00%)  15/184 (8.15%) 
Psychiatric disorders         
Agitation * 1  13/180 (7.22%)  11/182 (6.04%)  4/90 (4.44%)  19/184 (10.33%) 
Insomnia * 1  15/180 (8.33%)  16/182 (8.79%)  8/90 (8.89%)  18/184 (9.78%) 
Schizophrenia * 1  10/180 (5.56%)  7/182 (3.85%)  6/90 (6.67%)  18/184 (9.78%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA version 16
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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 Medical Affairs
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01396421     History of Changes
Other Study ID Numbers: 331-10-231
First Submitted: July 11, 2011
First Posted: July 18, 2011
Results First Submitted: August 4, 2015
Results First Posted: October 29, 2015
Last Update Posted: October 29, 2015