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A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated With Dementia of the Alzheimer's Type

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03548584
Recruitment Status : Completed
First Posted : June 7, 2018
Results First Posted : September 18, 2023
Last Update Posted : September 18, 2023
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Agitation Associated With Alzheimer's Dementia
Alzheimer Dementia
Interventions Drug: Brexpiprazole
Other: Placebo
Enrollment 345
Recruitment Details A total of 345 participants were randomized, and participated in the study from 16 May 2018 to 1 June 2022.
Pre-assignment Details  
Arm/Group Title Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo
Hide Arm/Group Description Participants followed a titration schedule, to gradually increase their dose from 0.5 milligrams per day (mg/day) in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 milligrams (mg), once daily until Week 12. Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 3 mg/day from Day 29. Participants continued to receive brexpiprazole 3 mg, once daily until Week 12. Participants received matching placebo, once daily for 12 weeks.
Period Title: Overall Study
Started 75 153 117
Intent-to-treat Population [1] 73 153 116
Completed 68 130 104
Not Completed 7 23 13
Reason Not Completed
Lost to Follow-up             0             0             1
Adverse Event             1             11             5
Site Terminated by Sponsor             1             3             2
Subject Withdrew Consent to Participate             5             5             3
Lack of Efficacy             0             1             0
Non-compliance with Study Drug             0             1             0
Reason not Specified (Not Related to Coronavirus Disease 2019 [COVID-19])             0             2             2
[1]
Intent-to-treat (ITT) Population consisted of all participants in the randomized sample, who took at least 1 dose of investigational medical product (IMP) and had a baseline and at least one post-baseline evaluation for the Cohen-Mansfield Agitation Inventory (CMAI) total score.
Arm/Group Title Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo Total
Hide Arm/Group Description Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 mg, once daily until Week 12. Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 3 mg/day from Day 29. Participants continued to receive brexpiprazole 3 mg, once daily until Week 12. Participants received matching placebo, once daily for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 75 153 117 345
Hide Baseline Analysis Population Description
Randomized Sample consisted of all participants who were randomized into this trial.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 75 participants 153 participants 117 participants 345 participants
74.3  (7.3) 74.6  (8.0) 73.0  (7.0) 74.0  (7.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 153 participants 117 participants 345 participants
Female
43
  57.3%
92
  60.1%
60
  51.3%
195
  56.5%
Male
32
  42.7%
61
  39.9%
57
  48.7%
150
  43.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 153 participants 117 participants 345 participants
Hispanic or Latino
25
  33.3%
46
  30.1%
37
  31.6%
108
  31.3%
Not Hispanic or Latino
50
  66.7%
107
  69.9%
80
  68.4%
237
  68.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 75 participants 153 participants 117 participants 345 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
3
   2.0%
1
   0.9%
4
   1.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
   6.7%
6
   3.9%
1
   0.9%
12
   3.5%
White
70
  93.3%
144
  94.1%
115
  98.3%
329
  95.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Cohen-Mansfield Agitation Inventory (CMAI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 75 participants 153 participants 117 participants 345 participants
78.6  (15.5) 81.2  (17.2) 79.4  (17.6) 80  (17)
[1]
Measure Description: The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior.
1.Primary Outcome
Title Change From Baseline to Week 12 in the CMAI Total Score
Hide Description The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. Mixed model repeated measures (MMRM) was used for the analysis. As prespecified in the statistical analysis plan (SAP), data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-22.6  (1.08) -17.3  (1.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.32
Confidence Interval (2-Sided) 95%
-8.77 to -1.87
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 12 in the Clinical Global Impression Severity of Illness (CGI-S) Score, as Related to Agitation
Hide Description CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 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. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.20  (0.06) -0.93  (0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.47 to -0.07
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 12 in CMAI Subscale Scores
Hide Description The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. It consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding, as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The four subscales include 12, 6, 4, and 2 items, respectively. The score of the subscale is the sum of the individual items included in the subscale, so the score range for each of the 4 subscales is 0 to 84, 0 to 42, 0 to 28, and 0 to 14, respectively. Higher scores indicate worsening of the condition. A negative change from baseline=improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Aggressive Behavior -9.09  (0.42) -7.13  (0.56)
Physically Nonaggressive Behavior -6.45  (0.40) -5.04  (0.53)
Verbally Agitated Behavior -4.39  (0.31) -3.14  (0.40)
Hiding and Hoarding -1.50  (0.17) -1.14  (0.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Aggressive Behavior
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0040
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.95
Confidence Interval (2-Sided) 95%
-3.28 to -0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Physically Nonaggressive Behavior
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0296
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.41
Confidence Interval (2-Sided) 95%
-2.68 to -0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Verbally Agitated Behavior
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0113
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-2.21 to -0.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Hiding and Hoarding
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1941
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.90 to 0.18
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in CMAI Total Score for Each Trial Visit During the Double-blind Treatment Period
Hide Description The CMAI score is used to assess the frequency of manifestations of agitated behaviors in participants. The CMAI consists of 29 agitated behaviors that are rated on a 7-point scale of frequency across four subscales of aggressive behavior, physically nonaggressive behavior, verbally agitated behavior and hiding and hoarding as: 1=never; 2=less than once a week; 3=once or twice a week; 4=several times a week; 5=once or twice a day; 6=several times a day; 7=several times an hour. The CMAI total score ranges from 29 to 203. Higher scores indicate worsening of the condition. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline, Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change From Baseline at Week 2 -5.76  (0.71) -6.61  (0.90)
Change From Baseline at Week 4 -12.1  (0.82) -11.0  (1.06)
Change From Baseline at Week 6 -16.2  (0.91) -13.9  (1.19)
Change From Baseline at Week 8 -19.4  (0.96) -14.4  (1.28)
Change From Baseline at Week 10 -22.2  (0.97) -15.7  (1.29)
Change From Baseline at Week 12 -22.6  (1.08) -17.3  (1.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change From Baseline at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4242
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
-1.24 to 2.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change From Baseline at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3665
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.14
Confidence Interval (2-Sided) 95%
-3.63 to 1.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1065
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.32
Confidence Interval (2-Sided) 95%
-5.15 to 0.50
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.08
Confidence Interval (2-Sided) 95%
-8.12 to -2.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.47
Confidence Interval (2-Sided) 95%
-9.54 to -3.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.32
Confidence Interval (2-Sided) 95%
-8.77 to -1.87
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in CGI-S for Each Trial Visit During the Double-Blind Treatment Period
Hide Description CGI-S was used to rate the severity of agitation. The score ranges from 0 to 7 with response choices as, 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. The higher the value, the more severe the agitation. A negative change from baseline indicates improvement. MMRM was used for the analysis. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline, Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Change From Baseline at Week 2 -0.21  (0.03) -0.27  (0.04)
Change From Baseline at Week 4 -0.53  (0.05) -0.50  (0.06)
Change From Baseline at Week 6 -0.74  (0.05) -0.68  (0.07)
Change From Baseline at Week 8 -0.97  (0.06) -0.70  (0.08)
Change From Baseline at Week 10 -1.14  (0.06) -0.86  (0.08)
Change From Baseline at Week 12 -1.20  (0.06) -0.93  (0.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3048
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.05 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7058
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.17 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4516
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.23 to 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0052
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.46 to -0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0060
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.47 to -0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments MMRM method with model terms of treatment, trial site, visit, treatment-by-visit and baseline-by-visit interaction were used for analysis.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-0.47 to -0.07
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Clinical Global Impressions-Improvement (CGI-I) Score at Each Trial Visit During the Double-Blind Treatment Period
Hide Description CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline, Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 2 Number Analyzed 221 participants 114 participants
3.70  (0.75) 3.57  (0.69)
Week 4 Number Analyzed 225 participants 116 participants
3.19  (0.85) 3.39  (0.87)
Week 6 Number Analyzed 225 participants 116 participants
2.92  (0.94) 3.19  (0.95)
Week 8 Number Analyzed 225 participants 116 participants
2.80  (1.00) 3.16  (1.01)
Week 10 Number Analyzed 225 participants 116 participants
2.62  (0.99) 2.97  (1.00)
Week 12 Number Analyzed 225 participants 116 participants
2.66  (1.09) 2.97  (1.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1975
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.05 to 0.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0084
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.44 to -0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0101
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.46 to -0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.59 to -0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-0.55 to -0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0070
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.57 to -0.09
Estimation Comments [Not Specified]
7.Secondary Outcome
Title CMAI Response Rate Assessed as Percentage of Participants With CMAI Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
Hide Description The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Measure Type: Number
Unit of Measure: percentage of participants
>/= 20%: Week 2 Number Analyzed 221 participants 114 participants
11.3 13.2
>/= 20%: Week 4 Number Analyzed 225 participants 116 participants
29.3 27.6
>/= 20%: Week 6 Number Analyzed 225 participants 116 participants
43.1 37.9
>/= 20%: Week 8 Number Analyzed 225 participants 116 participants
59.6 38.8
>/= 20%: Week 10 Number Analyzed 225 participants 116 participants
65.8 45.7
>/= 20%: Week 12 Number Analyzed 225 participants 116 participants
68.4 47.4
>/= 30%: Week 2 Number Analyzed 221 participants 114 participants
3.62 3.51
>/= 30%: Week 4 Number Analyzed 225 participants 116 participants
10.7 10.3
>/= 30%: Week 6 Number Analyzed 225 participants 116 participants
22.7 20.7
>/= 30%: Week 8 Number Analyzed 225 participants 116 participants
32.9 19.0
>/= 30%: Week 10 Number Analyzed 225 participants 116 participants
38.2 24.1
>/= 30%: Week 12 Number Analyzed 225 participants 116 participants
42.7 25.9
>/= 40%: Week 2 Number Analyzed 221 participants 114 participants
1.81 1.75
>/= 40%: Week 4 Number Analyzed 225 participants 116 participants
4.89 5.17
>/= 40%: Week 6 Number Analyzed 225 participants 116 participants
10.7 8.62
>/= 40%: Week 8 Number Analyzed 225 participants 116 participants
16.9 8.62
>/= 40%: Week 10 Number Analyzed 225 participants 116 participants
20.9 11.2
>/= 40%: Week 12 Number Analyzed 225 participants 116 participants
23.1 14.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/= 20%: Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7290
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.64 to 1.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=20%: Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6196
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.78 to 1.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=20%: Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2718
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.88 to 1.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=20%: Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
1.19 to 1.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=20%: Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
1.15 to 1.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=20%: Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
1.15 to 1.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7211
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.39 to 3.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7606
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.57 to 2.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5902
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.74 to 1.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
1.14 to 2.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0066
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
1.11 to 2.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=30%: Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
1.18 to 2.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9074
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.20 to 5.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9625
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.36 to 2.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5120
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.63 to 2.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0244
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.98
Confidence Interval (2-Sided) 95%
1.03 to 3.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0161
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
1.08 to 3.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments >/=40%: Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
1.00 to 2.61
Estimation Comments [Not Specified]
8.Secondary Outcome
Title CMAI Response Rate Assessed as Percentage of Participants With CMAI Response Based on Improvement From Baseline in Agitation Status at Every Scheduled Trial Visit in the Double-Blind Treatment Period
Hide Description The CMAI assesses frequency of agitated behaviors in elderly persons. The scale consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. Each of the agitated behaviors are scored 1 (never) to 7 (several times an hours), with the total scale score ranging from 29 to 203. Higher score indicates greater frequency of agitated behavior. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline, Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 Number Analyzed 221 participants 114 participants
8.14 14.0
Week 4 Number Analyzed 225 participants 116 participants
20.4 19.0
Week 6 Number Analyzed 225 participants 116 participants
33.8 26.7
Week 8 Number Analyzed 225 participants 116 participants
44.0 31.0
Week 10 Number Analyzed 225 participants 116 participants
50.2 34.5
Week 12 Number Analyzed 225 participants 116 participants
52.4 37.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1503
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.35 to 1.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7559
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.69 to 1.67
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2246
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.88 to 1.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0276
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
1.02 to 1.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.12 to 1.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
1.14 to 1.89
Estimation Comments [Not Specified]
9.Secondary Outcome
Title CGI-I Response Rate Assessed as Percentage of Participants With CGI-I Response at Every Scheduled Trial Visit in the Double-Blind Treatment Period
Hide Description CGI-I is a 7-point scale that requires the clinician to assess whether a participant's condition has improved or worsened relative to a baseline state at the beginning of the intervention. This was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Higher scores indicate worse condition. As prespecified in the SAP, data for this outcome measure was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Time Frame Baseline, Weeks 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT Population consisted of all participants in the randomized sample, who took at least 1 dose of IMP and had a baseline and at least one post-baseline evaluation for the CMAI total score. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified time point.
Arm/Group Title Brexpiprazole 2 and 3 mg Placebo
Hide Arm/Group Description:

Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15 or from 0.5 mg/day in the starting to 3 mg/day from Day 29.

Participants continued to receive brexpiprazole 2 or 3 mg, once daily until Week 12.

Participants received matching placebo, once daily for 12 weeks.
Overall Number of Participants Analyzed 225 116
Measure Type: Number
Unit of Measure: percentage of participants
Week 2 Number Analyzed 221 participants 114 participants
4.98 5.26
Week 4 Number Analyzed 225 participants 116 participants
21.8 12.1
Week 6 Number Analyzed 225 participants 116 participants
35.1 23.3
Week 8 Number Analyzed 225 participants 116 participants
44.4 24.1
Week 10 Number Analyzed 225 participants 116 participants
52.4 33.6
Week 12 Number Analyzed 225 participants 116 participants
52.4 40.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8549
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.40 to 3.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 4
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0093
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
1.14 to 3.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0083
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.56
Confidence Interval (2-Sided) 95%
1.10 to 2.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 8
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.85
Confidence Interval (2-Sided) 95%
1.32 to 2.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 10
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.57
Confidence Interval (2-Sided) 95%
1.18 to 2.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Brexpiprazole 2 and 3 mg, Placebo
Comments Week 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0160
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Response Rate
Estimated Value 1.32
Confidence Interval (2-Sided) 95%
1.03 to 1.69
Estimation Comments [Not Specified]
Time Frame From signing of informed consent up to end of study (Week 16)
Adverse Event Reporting Description Randomized Sample was used to assess all-cause mortality. It consisted of all participants who were randomized into this trial. Safety Sample was used to assess serious adverse events (SAEs) and other adverse events (AEs) and consisted of all participants who were administered at least one dose of IMP.
 
Arm/Group Title Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo
Hide Arm/Group Description Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 2 mg/day from Day 15. Participants continued to receive brexpiprazole 2 mg, once daily until Week 12. Participants followed a titration schedule, to gradually increase their dose from 0.5 mg/day in the starting to 3 mg/day from Day 29. Participants continued to receive brexpiprazole 3 mg, once daily until Week 12. Participants received matching placebo, once daily for 12 weeks.
All-Cause Mortality
Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/75 (0.00%)   1/153 (0.65%)   0/117 (0.00%) 
Hide Serious Adverse Events
Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/73 (0.00%)   6/153 (3.92%)   3/116 (2.59%) 
Cardiac disorders       
Cardiac failure  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Infections and infestations       
Covid-19  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Pneumonia  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Urinary tract infection  1  0/73 (0.00%)  2/153 (1.31%)  0/116 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Hip fracture  1  0/73 (0.00%)  1/153 (0.65%)  1/116 (0.86%) 
Investigations       
Sars-Cov-2 test positive  1  0/73 (0.00%)  0/153 (0.00%)  1/116 (0.86%) 
Metabolism and nutrition disorders       
Cachexia  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Dehydration  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Metabolic acidosis  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Psychiatric disorders       
Mental status change  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Psychotic disorder  1  0/73 (0.00%)  0/153 (0.00%)  1/116 (0.86%) 
Renal and urinary disorders       
Acute kidney injury  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
Vascular disorders       
Hypertension  1  0/73 (0.00%)  1/153 (0.65%)  0/116 (0.00%) 
1
Term from vocabulary, MedDRA (25.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Brexpiprazole 2 mg Brexpiprazole 3 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/73 (6.85%)   10/153 (6.54%)   8/116 (6.90%) 
Nervous system disorders       
Headache  1  5/73 (6.85%)  10/153 (6.54%)  8/116 (6.90%) 
1
Term from vocabulary, MedDRA (25.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Trials
Organization: Otsuka Pharmaceutical Co., LTD.
Phone: +81-3-6361-7366
EMail: CL_OPCJ_RDA_Team@otsuka.jp
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT03548584    
Other Study ID Numbers: 331-14-213
First Submitted: May 7, 2018
First Posted: June 7, 2018
Results First Submitted: May 31, 2023
Results First Posted: September 18, 2023
Last Update Posted: September 18, 2023