Schizophrenia
Conditions
Brief summary
To investigate the efficacy and safety of OPC-34712 in comparison with placebo in patients with schizophrenia.
Interventions
DRUGOPC-34712
orally administered once daily
DRUGPlacebo
orally administered once daily
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients age 18 years or older to less than 65 years (at time of informed consent) diagnosed with schizophrenia based on DSM-IV-TR diagnostic criteria * Patients who are hospitalized, or judged to required hospitalization, for acute relapse of schizophrenia at time of informed consent * Patients who are experiencing acute exacerbation of psychotic symptoms
Exclusion criteria
* Female patients who are breastfeeding or who have a positive pregnancy test (urine) result prior to receiving investigational medicinal product * Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator * Patients who are diagnosed with a disease other than schizophrenia (schizoaffective disorder, major depressive disorder, bipolar disorder, posttraumatic stress disorder, anxiety disorder, delirium, dementia, amnesia, or other cognitive disorder) based on current DSM-IV-TR Axis Ι criteria, or who are diagnosed with a personality disorder (borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome). |
| Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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 social 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). |
| Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | Severity of illness for each participant was rated using the CGI-S, which was the 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. |
| Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 1mg Brexpiprazole 1 mg tablet once daily for 6 weeks. | 115 |
| Brexpiprazole 2mg Brexpiprazole 2 mg tablet once daily for 6 weeks. | 115 |
| Brexpiprazole 4mg Brexpiprazole 4 mg tablet once daily for 6 weeks. | 113 |
| Placebo Placebo tablet once daily for 6 weeks. | 116 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 19 | 12 | 18 | 21 |
| Overall Study | Lack of Efficacy | 7 | 9 | 9 | 7 |
| Overall Study | Physician Decision | 2 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 11 | 16 | 17 |
| Overall Study | Withdrawal Criteria | 1 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Brexpiprazole 2mg | Brexpiprazole 4mg | Brexpiprazole 1mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 115 Participants | 113 Participants | 115 Participants | 116 Participants | 459 Participants |
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12 | 44.1 years STANDARD_DEVIATION 11.9 | 44.7 years STANDARD_DEVIATION 11.5 | 45.0 years STANDARD_DEVIATION 11.9 | 44.3 years STANDARD_DEVIATION 11.8 |
| Region of Enrollment Japan | 115 participants | 113 participants | 115 participants | 116 participants | 459 participants |
| Sex: Female, Male Female | 54 Participants | 58 Participants | 64 Participants | 65 Participants | 241 Participants |
| Sex: Female, Male Male | 61 Participants | 55 Participants | 51 Participants | 51 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 115 | 0 / 114 | 0 / 113 | 0 / 116 |
| other Total, other adverse events | 49 / 115 | 46 / 114 | 49 / 113 | 56 / 116 |
| serious Total, serious adverse events | 8 / 115 | 5 / 114 | 5 / 113 | 5 / 116 |
Outcome results
Primary
Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score
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
Population: Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week1 | -2.68 units on a scale | Standard Error 1.04 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week2 | -5.07 units on a scale | Standard Error 1.36 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week3 | -6.92 units on a scale | Standard Error 1.6 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week4 | -8.40 units on a scale | Standard Error 1.81 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week5 | -8.13 units on a scale | Standard Error 2.02 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week6 | -8.26 units on a scale | Standard Error 2.1 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week6 | -14.95 units on a scale | Standard Error 2 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week4 | -12.35 units on a scale | Standard Error 1.74 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week1 | -4.59 units on a scale | Standard Error 1.03 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week3 | -11.00 units on a scale | Standard Error 1.55 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week2 | -7.93 units on a scale | Standard Error 1.33 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week5 | -13.97 units on a scale | Standard Error 1.93 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week2 | -6.80 units on a scale | Standard Error 1.36 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week3 | -9.42 units on a scale | Standard Error 1.59 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week4 | -11.21 units on a scale | Standard Error 1.8 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week6 | -11.49 units on a scale | Standard Error 2.1 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week5 | -11.09 units on a scale | Standard Error 2.01 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week1 | -3.42 units on a scale | Standard Error 1.05 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week5 | -6.62 units on a scale | Standard Error 2.03 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week6 | -7.63 units on a scale | Standard Error 2.11 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week2 | -4.54 units on a scale | Standard Error 1.34 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week4 | -5.67 units on a scale | Standard Error 1.8 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week1 | -3.09 units on a scale | Standard Error 1.03 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score | Week3 | -6.00 units on a scale | Standard Error 1.58 |
Secondary
Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S)
Severity of illness for each participant was rated using the CGI-S, which was the 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
Population: Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week1 | -0.13 units on a scale | Standard Error 0.06 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week2 | -0.26 units on a scale | Standard Error 0.08 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week3 | -0.38 units on a scale | Standard Error 0.09 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week4 | -0.48 units on a scale | Standard Error 0.09 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week5 | -0.45 units on a scale | Standard Error 0.11 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week6 | -0.52 units on a scale | Standard Error 0.11 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week6 | -0.85 units on a scale | Standard Error 0.11 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week4 | -0.62 units on a scale | Standard Error 0.09 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week1 | -0.18 units on a scale | Standard Error 0.06 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week3 | -0.52 units on a scale | Standard Error 0.09 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week2 | -0.36 units on a scale | Standard Error 0.08 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week5 | -0.81 units on a scale | Standard Error 0.1 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week2 | -0.34 units on a scale | Standard Error 0.08 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week3 | -0.50 units on a scale | Standard Error 0.09 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week4 | -0.50 units on a scale | Standard Error 0.09 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week6 | -0.62 units on a scale | Standard Error 0.11 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week5 | -0.56 units on a scale | Standard Error 0.1 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week1 | -0.09 units on a scale | Standard Error 0.06 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week5 | -0.52 units on a scale | Standard Error 0.11 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week6 | -0.57 units on a scale | Standard Error 0.11 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week2 | -0.25 units on a scale | Standard Error 0.08 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week4 | -0.40 units on a scale | Standard Error 0.09 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week1 | -0.15 units on a scale | Standard Error 0.06 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity of Illness (CGI-S) | Week3 | -0.36 units on a scale | Standard Error 0.09 |
Secondary
Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score.
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 social 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
Population: EEfficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week2 | -1.08 units on a scale | Standard Error 0.37 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week6 | -2.34 units on a scale | Standard Error 0.55 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week3 | -1.64 units on a scale | Standard Error 0.41 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week5 | -2.31 units on a scale | Standard Error 0.52 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week1 | -0.54 units on a scale | Standard Error 0.27 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week4 | -2.36 units on a scale | Standard Error 0.46 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week5 | -3.24 units on a scale | Standard Error 0.5 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week4 | -2.90 units on a scale | Standard Error 0.44 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week1 | -0.83 units on a scale | Standard Error 0.27 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week2 | -1.46 units on a scale | Standard Error 0.36 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week6 | -3.48 units on a scale | Standard Error 0.52 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week3 | -2.41 units on a scale | Standard Error 0.39 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week1 | -0.71 units on a scale | Standard Error 0.27 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week2 | -1.76 units on a scale | Standard Error 0.36 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week3 | -2.27 units on a scale | Standard Error 0.4 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week4 | -2.94 units on a scale | Standard Error 0.46 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week5 | -3.19 units on a scale | Standard Error 0.52 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week6 | -3.24 units on a scale | Standard Error 0.55 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week6 | -1.20 units on a scale | Standard Error 0.55 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week5 | -0.85 units on a scale | Standard Error 0.52 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week2 | -0.72 units on a scale | Standard Error 0.36 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week1 | -0.59 units on a scale | Standard Error 0.27 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week4 | -0.81 units on a scale | Standard Error 0.46 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week3 | -1.14 units on a scale | Standard Error 0.4 |
Secondary
Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score.
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, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).
Time frame: Baseline, Weeks 1, 2, 3, 4, 5, and 6
Population: Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week1 | -0.96 units on a scale | Standard Error 0.36 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week2 | -1.72 units on a scale | Standard Error 0.45 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week3 | -2.07 units on a scale | Standard Error 0.52 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week4 | -2.39 units on a scale | Standard Error 0.57 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week5 | -2.19 units on a scale | Standard Error 0.62 |
| Brexpiprazole 1mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week6 | -2.22 units on a scale | Standard Error 0.64 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week6 | -4.32 units on a scale | Standard Error 0.61 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week4 | -3.69 units on a scale | Standard Error 0.54 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week1 | -1.31 units on a scale | Standard Error 0.36 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week3 | -3.21 units on a scale | Standard Error 0.51 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week2 | -2.31 units on a scale | Standard Error 0.44 |
| Brexpiprazole 2mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week5 | -4.05 units on a scale | Standard Error 0.6 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week2 | -1.61 units on a scale | Standard Error 0.45 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week3 | -2.71 units on a scale | Standard Error 0.52 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week4 | -3.09 units on a scale | Standard Error 0.56 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week6 | -3.15 units on a scale | Standard Error 0.64 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week5 | -2.89 units on a scale | Standard Error 0.62 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week1 | -0.70 units on a scale | Standard Error 0.36 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week5 | -3.26 units on a scale | Standard Error 0.63 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week6 | -3.69 units on a scale | Standard Error 0.64 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week2 | -2.25 units on a scale | Standard Error 0.44 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week4 | -2.90 units on a scale | Standard Error 0.56 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week1 | -1.09 units on a scale | Standard Error 0.35 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week3 | -2.57 units on a scale | Standard Error 0.52 |
Secondary
Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6.
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: Baseline, Weeks 1, 2, 3, 4, 5, and 6
Population: Efficacy sample（FAS : Full Analysis Set） consisted of all participants who received at least one dose of study medication and have Baseline and at least one Post-Baseline PANSS total score evaluation.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week1 | 3.87 units on a scale | Standard Deviation 0.92 |
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week2 | 3.87 units on a scale | Standard Deviation 1.1 |
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week3 | 3.89 units on a scale | Standard Deviation 1.2 |
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week4 | 3.83 units on a scale | Standard Deviation 1.23 |
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week5 | 3.92 units on a scale | Standard Deviation 1.27 |
| Brexpiprazole 1mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week6 | 3.90 units on a scale | Standard Deviation 1.32 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week6 | 3.49 units on a scale | Standard Deviation 1.3 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week4 | 3.51 units on a scale | Standard Deviation 1.16 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week1 | 3.84 units on a scale | Standard Deviation 0.96 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week3 | 3.53 units on a scale | Standard Deviation 1.04 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week2 | 3.68 units on a scale | Standard Deviation 1.02 |
| Brexpiprazole 2mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week5 | 3.42 units on a scale | Standard Deviation 1.23 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week2 | 3.79 units on a scale | Standard Deviation 1.13 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week3 | 3.77 units on a scale | Standard Deviation 1.2 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week4 | 3.81 units on a scale | Standard Deviation 1.23 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week6 | 3.78 units on a scale | Standard Deviation 1.33 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week5 | 3.76 units on a scale | Standard Deviation 1.3 |
| Brexpiprazole 4mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week1 | 4.01 units on a scale | Standard Deviation 0.93 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week5 | 3.86 units on a scale | Standard Deviation 1.48 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week6 | 3.83 units on a scale | Standard Deviation 1.49 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week2 | 3.88 units on a scale | Standard Deviation 1.26 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week4 | 3.90 units on a scale | Standard Deviation 1.36 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week1 | 3.92 units on a scale | Standard Deviation 1.04 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | Week3 | 3.92 units on a scale | Standard Deviation 1.36 |