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Efficacy Study of OPC-34712 in Adults With Acute Schizophrenia (BEACON)

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ClinicalTrials.gov Identifier: NCT01393613
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : November 26, 2015
Last Update Posted : November 26, 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
Drug: Placebo
Enrollment 674
Recruitment Details This trial was conducted in 674 participants from 68 trial sites in 8 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 (MINI) for schizophrenia and psychotic disorders studies were included.
Arm/Group Title Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
Period Title: Overall Study
Started 120 186 184 184
Completed 81 129 130 118
Not Completed 39 57 54 66
Reason Not Completed
Adverse Event             11             11             13             22
Participant Met Withdrawal Criteria             0             0             2             1
Physician Decision             2             0             0             1
Withdrawal by Subject             15             25             23             21
Protocol Deviation             2             1             0             0
Lack of Efficacy             9             20             16             21
Arm/Group Title Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo Total
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks. Total of all reporting groups
Overall Number of Baseline Participants 120 186 184 184 674
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 120 participants 186 participants 184 participants 184 participants 674 participants
39.1  (11.9) 36.9  (10.9) 38.6  (11.0) 39.3  (10.8) 38.4  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 120 participants 186 participants 184 participants 184 participants 674 participants
Female
43
  35.8%
64
  34.4%
71
  38.6%
73
  39.7%
251
  37.2%
Male
77
  64.2%
122
  65.6%
113
  61.4%
111
  60.3%
423
  62.8%
1.Primary Outcome
Title Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score.
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -3.32  (0.83) -4.35  (0.68) -5.58  (0.68) -3.48  (0.68)
Week 2 -7.61  (1.09) -8.70  (0.88) -8.42  (0.88) -6.61  (0.89)
Week 3 -11.56  (1.30) -10.69  (1.06) -12.63  (1.05) -8.95  (1.06)
Week 4 -13.97  (1.49) -13.12  (1.21) -15.55  (1.19) -11.10  (1.22)
Week 5 -14.47  (1.71) -14.11  (1.38) -17.26  (1.37) -11.89  (1.40)
Week 6 -16.90  (1.86) -16.61  (1.49) -20.00  (1.48) -13.53  (1.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare the average effect analysis for brexpiprazole 2 mg/day and 4 mg/day and placebo combined treatment groups at Week 6. The primary analysis was performed by fitting a Mixed Model Repeated Measures (MMRM) with an unstructured variance covariance structure. The model included fixed class effect terms for treatment, trial site, visit week, baseline, baseline and visit interaction and an interaction term of treatment by visit week.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0093
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.47
Confidence Interval (2-Sided) 95%
-10.6 to -2.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1448
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.08
Confidence Interval (2-Sided) 95%
-7.23 to 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6. MMRM analysis fixed effect of treatment, clinical visit, trial site, treatment visit interaction, Baseline value, and Baseline visit interaction as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1588
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.37
Confidence Interval (2-Sided) 95%
-8.06 to 1.32
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score.
Hide Description Severity of illness for each participant was rated using the CGI-S, which was the key secondary efficacy endpoint. To perform this assessment, the 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 participants.
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 120 180 183 181
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.11  (0.05) -0.16  (0.04) -0.22  (0.04) -0.12  (0.04)
Week 2 -0.31  (0.06) -0.40  (0.05) -0.40  (0.05) -0.36  (0.05)
Week 3 -0.63  (0.07) -0.60  (0.06) -0.69  (0.06) -0.44  (0.06)
Week 4 -0.67  (0.09) -0.72  (0.07) -0.85  (0.07) -0.58  (0.07)
Week 5 -0.81  (0.10) -0.79  (0.08) -1.02  (0.08) -0.68  (0.08)
Week 6 -0.91  (0.11) -0.99  (0.09) -1.19  (0.08) -0.81  (0.09)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare the average effect analysis for brexpiprazole 2 mg/day and 4 mg/day and placebo combined treatment groups at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0069
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6. The analysis of this key secondary endpoint was conducted if both comparisons of brexpiprazole 4 mg/day vs placebo and brexpiprazole 2 mg/day vs placebo of the primary endpoint were significant. Because only the comparison of brexpiprazole 4 mg/day vs placebo met the threshold in the primary analysis, the following analysis is not part of the formal statistical testing and is descriptive only.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.62 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 Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1269
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.42 to -0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4449
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.37 to 0.16
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score.
Hide Description PSP is a validated clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (e.g. 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, Week 3 and Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 105 170 174 163
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 3 6.97  (0.90) 6.85  (0.73) 7.12  (0.71) 5.80  (0.73)
Week 6 11.73  (1.19) 10.52  (0.95) 13.11  (0.94) 8.52  (0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.59
Confidence Interval (2-Sided) 95%
2.02 to 7.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1286
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.00
Confidence Interval (2-Sided) 95%
-0.58 to 4.59
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0332
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.21
Confidence Interval (2-Sided) 95%
0.26 to 6.16
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score.
Hide Description PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). The analysis of secondary endpoints was conducted if both comparisons of brexpiprazole 4 mg/day vs placebo and brexpiprazole 2 mg/day vs placebo of the primary endpoint were significant. Although only the comparison of brexpiprazole 4 mg/day vs placebo met the gatekeeping threshold in the primary analysis, statistical testing for the other doses was reported for information.
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.93  (0.28) -1.43  (0.23) -1.80  (0.23) -1.25  (0.23)
Week 2 -2.54  (0.39) -2.76  (0.32) -2.93  (0.32) -2.56  (0.32)
Week 3 -3.94  (0.46) -3.56  (0.37) -4.43  (0.37) -3.34  (0.37)
Week 4 -4.83  (0.52) -4.35  (0.42) -5.16  (0.41) -3.93  (0.42)
Week 5 -4.80  (0.58) -4.68  (0.47) -6.04  (0.46) -4.33  (0.47)
Week 6 -5.63  (0.62) -5.42  (0.50) -6.65  (0.50) -4.95  (0.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0166
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.70
Confidence Interval (2-Sided) 95%
-3.08 to -0.31
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5101
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-1.86 to 0.93
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3938
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-2.26 to 0.89
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score.
Hide Description The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.31  (0.25) -0.52  (0.20) -0.88  (0.20) -0.40  (0.20)
Week 2 -1.27  (0.29) -1.31  (0.23) -1.42  (0.23) -0.79  (0.24)
Week 3 -2.06  (0.35) -1.80  (0.28) -2.15  (0.28) -1.18  (0.28)
Week 4 -2.56  (0.40) -2.09  (0.32) -2.69  (0.32) -1.67  (0.33)
Week 5 -2.71  (0.44) -2.50  (0.35) -2.82  (0.35) -1.74  (0.36)
Week 6 -2.92  (0.48) -2.91  (0.38) -3.36  (0.38) -2.14  (0.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0231
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.22
Confidence Interval (2-Sided) 95%
-2.28 to -0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1547
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-1.83 to 0.29
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2004
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.78
Confidence Interval (2-Sided) 95%
-1.98 to 0.42
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6.
Hide Description The efficacy of trial medication was rated for each participant using the CGI-I. The study physician would rate the participant's total improvement whether or not it is due entirely to drug treatment. All responses were compared to the participant's condition at Baseline prior to the first dose of double-blind study medication. Response choices included: 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 sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 120 180 183 181
Mean (Standard Deviation)
Unit of Measure: Units on a scale
3.20  (1.45) 3.17  (1.34) 2.95  (1.33) 3.48  (1.46)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenzel (CMH) row mean scores differ test controlling for study center.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.49
Confidence Interval (2-Sided) 95%
-0.78 to -0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0422
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH row mean scores differ test controlling for study center.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.60 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1358
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH row mean scores differ test controlling for study center.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.56 to 0.08
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Response at Week 6.
Hide Description The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of 1 or 2.
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Measure Type: Number
Unit of Measure: percentage of participants
43.6 38.5 49.7 31.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
1.20 to 2.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1680
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.92 to 1.62
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0433
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
1.02 to 1.79
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6.
Hide Description Participants discontinued for lack of efficacy during the trial were reported here.
Time Frame Week 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Measure Type: Number
Unit of Measure: percentage of participants
7.69 11.2 8.84 11.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5202
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.44 to 1.51
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9894
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.55 to 1.85
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4586
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments CMH general association test
Method of Estimation Estimation Parameter Relative Risk
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.36 to 1.59
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score.
Hide Description The PEC score consisted of five PANSS items: excitement (P4), hostility (P7), tension (G4), uncooperativeness (G8), and poor impulse control (G14). Each of the items were rated on a scale of 1 (absent) to 7 (extreme). The PEC scores ranged from 5 (not present) to 35 (extremely severe).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.35  (0.25) -0.46  (0.21) -1.01  (0.21) -0.48  (0.21)
Week 2 -0.76  (0.32) -1.31  (0.26) -1.21  (0.26) -0.62  (0.26)
Week 3 -1.21  (0.35) -1.31  (0.28) -1.81  (0.28) -0.82  (0.29)
Week 4 -1.58  (0.37) -1.52  (0.29) -2.12  (0.29) -1.12  (0.30)
Week 5 -1.16  (0.42) -1.48  (0.34) -2.27  (0.34) -0.97  (0.35)
Week 6 -1.94  (0.41) -1.90  (0.33) -2.86  (0.33) -1.47  (0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0029
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.30 to -0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3559
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.34 to 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3646
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-1.51 to 0.56
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score.
Hide Description Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -1.44  (0.29) -1.77  (0.23) -1.75  (0.24) -1.30  (0.24)
Week 2 -2.97  (0.39) -3.10  (0.32) -3.03  (0.32) -3.03  (0.32)
Week 3 -4.48  (0.47) -4.09  (0.38) -4.39  (0.37) -3.78  (0.38)
Week 4 -5.42  (0.53) -4.93  (0.43) -5.48  (0.43) -4.67  (0.44)
Week 5 -5.86  (0.58) -5.35  (0.47) -6.41  (0.46) -5.47  (0.47)
Week 6 -6.56  (0.66) -6.26  (0.53) -7.05  (0.53) -5.91  (0.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1273
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-2.61 to 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6400
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-1.83 to 1.12
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4423
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.65
Confidence Interval (2-Sided) 95%
-2.32 to 1.01
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score.
Hide Description Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.70  (0.28) -0.85  (0.22) -1.12  (0.23) -0.66  (0.22)
Week 2 -1.71  (0.32) -1.86  (0.26) -1.72  (0.26) -1.38  (0.26)
Week 3 -2.55  (0.37) -2.30  (0.30) -2.64  (0.30) -1.83  (0.30)
Week 4 -3.21  (0.43) -2.63  (0.34) -3.17  (0.34) -2.16  (0.35)
Week 5 -3.35  (0.47) -3.13  (0.38) -3.21  (0.37) -2.24  (0.38)
Week 6 -3.55  (0.48) -3.53  (0.39) -3.84  (0.39) -2.55  (0.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0194
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.28
Confidence Interval (2-Sided) 95%
-2.36 to -0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0754
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.98
Confidence Interval (2-Sided) 95%
-2.06 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1080
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.00
Confidence Interval (2-Sided) 95%
-2.22 to 0.22
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score.
Hide Description Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -0.40  (0.23) -0.46  (0.19) -0.78  (0.19) -0.42  (0.19)
Week 2 -1.42  (0.27) -1.15  (0.22) -1.37  (0.22) -0.71  (0.23)
Week 3 -2.35  (0.31) -1.71  (0.25) -2.32  (0.25) -1.35  (0.26)
Week 4 -2.56  (0.36) -2.27  (0.29) -2.83  (0.29) -1.77  (0.30)
Week 5 -2.95  (0.41) -2.55  (0.33) -3.42  (0.32) -2.01  (0.33)
Week 6 -3.46  (0.43) -2.94  (0.35) -3.98  (0.34) -2.59  (0.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6. 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.39
Confidence Interval (2-Sided) 95%
-2.34 to -0.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4753
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-1.31 to 0.61
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1150
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.87
Confidence Interval (2-Sided) 95%
-1.96 to 0.21
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score.
Hide Description Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 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).
Placebo 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).
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 0.03  (0.22) -0.10  (0.18) -0.63  (0.18) -0.21  (0.18)
Week 2 -0.15  (0.28) -0.65  (0.23) -0.68  (0.23) -0.13  (0.23)
Week 3 -0.46  (0.30) -0.61  (0.24) -1.16  (0.24) -0.19  (0.24)
Week 4 -0.74  (0.32) -0.74  (0.26) -1.31  (0.25) -0.39  (0.26)
Week 5 -0.34  (0.36) -0.60  (0.29) -1.50  (0.29) -0.22  (0.30)
Week 6 -0.90  (0.36) -0.81  (0.29) -1.89  (0.29) -0.64  (0.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.26
Confidence Interval (2-Sided) 95%
-2.05 to -0.46
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6792
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.97 to 0.63
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5752
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.16 to 0.65
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score.
Hide Description Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).
Time Frame Baseline, Weeks 1, 2, 3, 4, 5, and 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy sample consisted 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 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description:
Brexpiprazole 1 mg tablet once daily for 6 weeks.
Brexpiprazole 2 mg tablet once daily for 6 weeks.
Brexpiprazole 4 mg tablet once daily for 6 weeks.
Placebo tablet once daily for 6 weeks.
Overall Number of Participants Analyzed 117 179 181 180
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
Week 1 -1.18  (0.22) -1.10  (0.18) -1.26  (0.18) -0.96  (0.18)
Week 2 -1.86  (0.27) -1.91  (0.22) -1.60  (0.22) -1.47  (0.22)
Week 3 -2.43  (0.28) -2.10  (0.23) -2.24  (0.23) -1.97  (0.23)
Week 4 -2.85  (0.29) -2.70  (0.23) -2.93  (0.23) -2.60  (0.23)
Week 5 -2.93  (0.31) -2.87  (0.25) -3.09  (0.25) -2.69  (0.26)
Week 6 -3.57  (0.30) -3.62  (0.24) -3.78  (0.24) -2.93  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 4 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0104
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.86
Confidence Interval (2-Sided) 95%
-1.51 to -0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0373
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.70
Confidence Interval (2-Sided) 95%
-1.35 to -0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 1 mg, Placebo
Comments Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0890
Comments [Not Specified]
Method Mixed Models Analysis
Comments MMRM analysis fixed effect of treatment, trial site, visit, treatment visit interaction, Baseline value, Baseline visit interaction as covariates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-1.39 to 0.10
Estimation Comments [Not Specified]
Time Frame Adverse events were monitored from signing of the informed consent form until follow-up for up to 30 (+2) days after the last dose of study medication.
Adverse Event Reporting Description A serious adverse event (SAE) was an untoward medical occurrence that resulted in death or required inpatient hospitalization or prolonged hospitalization. An AE was an exacerbation of an existing problem or a new problem experienced by a participant when enrolled in a trial whether or not it was considered drug related by study physician.
 
Arm/Group Title Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Hide Arm/Group Description Brexpiprazole 1 mg tablet once daily for 6 weeks. Brexpiprazole 2 mg tablet once daily for 6 weeks. Brexpiprazole 4 mg tablet once daily for 6 weeks. Placebo tablet once daily for 6 weeks.
All-Cause Mortality
Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/120 (2.50%)   4/186 (2.15%)   4/184 (2.17%)   10/184 (5.43%) 
General disorders         
Irritability * 1  0/120 (0.00%)  0/186 (0.00%)  0/184 (0.00%)  1/184 (0.54%) 
Psychiatric disorders         
Acute psychosis * 1  0/120 (0.00%)  0/186 (0.00%)  0/184 (0.00%)  1/184 (0.54%) 
Aggression * 1  1/120 (0.83%)  0/186 (0.00%)  0/184 (0.00%)  0/184 (0.00%) 
Psychotic disorder * 1  1/120 (0.83%)  2/186 (1.08%)  1/184 (0.54%)  1/184 (0.54%) 
Schizophrenia * 1  1/120 (0.83%)  2/186 (1.08%)  3/184 (1.63%)  8/184 (4.35%) 
Suicidal ideation * 1  0/120 (0.00%)  0/186 (0.00%)  1/184 (0.54%)  0/184 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole 1 mg Brexpiprazole 2 mg Brexpiprazole 4 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/120 (30.83%)   65/186 (34.95%)   66/184 (35.87%)   71/184 (38.59%) 
Gastrointestinal disorders         
Dyspepsia * 1  7/120 (5.83%)  7/186 (3.76%)  6/184 (3.26%)  6/184 (3.26%) 
Nervous system disorders         
Akathisia * 1  5/120 (4.17%)  9/186 (4.84%)  12/184 (6.52%)  13/184 (7.07%) 
Headache * 1  9/120 (7.50%)  20/186 (10.75%)  19/184 (10.33%)  27/184 (14.67%) 
Psychiatric disorders         
Agitation * 1  10/120 (8.33%)  16/186 (8.60%)  13/184 (7.07%)  13/184 (7.07%) 
Insomnia * 1  15/120 (12.50%)  25/186 (13.44%)  28/184 (15.22%)  27/184 (14.67%) 
Schizophrenia * 1  4/120 (3.33%)  6/186 (3.23%)  7/184 (3.80%)  10/184 (5.43%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 16.0
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 and Commercialization, Inc.
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01393613     History of Changes
Other Study ID Numbers: 331-10-230
First Submitted: July 11, 2011
First Posted: July 13, 2011
Results First Submitted: August 11, 2015
Results First Posted: November 26, 2015
Last Update Posted: November 26, 2015