Acute Schizophrenia
Conditions
Brief summary
The purpose of this study is to assess the efficacy, safety, and tolerability of fixed doses of OPC-34712 versus placebo for the treatment of adult subjects with an acute relapse of schizophrenia.
Detailed description
Schizophrenia is a severely debilitating mental illness that affects approximately 1% of the world population. Hallucinations and delusions are the most striking characteristic positive symptoms of schizophrenia; however, more subtle negative symptoms (eg, social withdrawal and lack of emotion, energy, and motivation) may also be present. The first antipsychotics developed for the treatment of schizophrenia were effective against positive symptoms, but showed little efficacy for negative symptoms and were also associated with a high incidence of side effects. Second generation antipsychotics, represent a significant advancement in the treatment of psychotic disorders because they are effective and at the same time exhibit fewer side effects than first generation antipsychotics. Although generally safer than first generation antipsychotics, the second-generation antipsychotics are not devoid of undesirable side effects such as Hyperprolactinemia and weight gain. In addition, the safety of these drugs vary considerably.
Interventions
DRUGOPC-34712
Higher dose tablet, once daily, for six weeks,
DRUGPlacebo
Placebo, once daily, for six weeks
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
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
1. Male or female subjects between 18 and 65 years of age, with a diagnosis of schizophrenia, as defined by DSM-IV-TR criteria 2. Subjects who have been recently hospitalized or who would benefit from hospitalization for an acute relapse of schizophrenia 3. Subjects experiencing an acute exacerbation of psychotic symptoms 4. Other protocol specific inclusion criteria may apply
Exclusion criteria
1. Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug 2. Subjects with a current DSM-IV-TR Axis I diagnosis of: * Schizoaffective disorder * MDD * Bipolar disorder * Delirium, dementia, amnestic or other cognitive disorder * Borderline, paranoid, histrionic, schizotypal, schizoid or antisocial personality disorder 3. Subjects presenting with a first episode of schizophrenia 4. Other protocol specific
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 Personal and Social Performance (PSP) Score. | Baseline, Week 3 and Week 6 | 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. |
| 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/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. |
| 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 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 Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | 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. |
| Percentage of Participants With Response at Week 6. | Week 6 | The response rate was defined as reduction of ≥30% from Baseline in PANSS Total Score or CGI-I score of 1 or 2. |
| Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. | Week 6 | Participants discontinued for lack of efficacy during the trial were reported here. |
| Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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. |
| Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
| Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
| Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
| Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
| Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
| Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Baseline, Weeks 1, 2, 3, 4, 5, and 6 | 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). |
Countries
Colombia, Croatia, Mexico, Philippines, Russia, Slovakia, Taiwan, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 1 mg Brexpiprazole 1 mg tablet once daily for 6 weeks. | 120 |
| Brexpiprazole 2 mg Brexpiprazole 2 mg tablet once daily for 6 weeks. | 186 |
| Brexpiprazole 4 mg Brexpiprazole 4 mg tablet once daily for 6 weeks. | 184 |
| Placebo Placebo tablet once daily for 6 weeks. | 184 |
| Total | 674 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 11 | 13 | 22 |
| Overall Study | Lack of Efficacy | 9 | 20 | 16 | 21 |
| Overall Study | Participant Met Withdrawal Criteria | 0 | 0 | 2 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 1 |
| Overall Study | Protocol Deviation | 2 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 25 | 23 | 21 |
Baseline characteristics
| Characteristic | Brexpiprazole 1 mg | Brexpiprazole 2 mg | Brexpiprazole 4 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 39.1 Years STANDARD_DEVIATION 11.9 | 36.9 Years STANDARD_DEVIATION 10.9 | 38.6 Years STANDARD_DEVIATION 11 | 39.3 Years STANDARD_DEVIATION 10.8 | 38.4 Years STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 43 Participants | 64 Participants | 71 Participants | 73 Participants | 251 Participants |
| Sex: Female, Male Male | 77 Participants | 122 Participants | 113 Participants | 111 Participants | 423 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 120 | 65 / 186 | 66 / 184 | 71 / 184 |
| serious Total, serious adverse events | 3 / 120 | 4 / 186 | 4 / 184 | 10 / 184 |
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 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -3.32 Units on a scale | Standard Error 0.83 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -7.61 Units on a scale | Standard Error 1.09 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -11.56 Units on a scale | Standard Error 1.3 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -13.97 Units on a scale | Standard Error 1.49 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -14.47 Units on a scale | Standard Error 1.71 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 | -16.90 Units on a scale | Standard Error 1.86 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 | -16.61 Units on a scale | Standard Error 1.49 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -13.12 Units on a scale | Standard Error 1.21 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -4.35 Units on a scale | Standard Error 0.68 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -10.69 Units on a scale | Standard Error 1.06 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -8.70 Units on a scale | Standard Error 0.88 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -14.11 Units on a scale | Standard Error 1.38 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -8.42 Units on a scale | Standard Error 0.88 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -12.63 Units on a scale | Standard Error 1.05 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -15.55 Units on a scale | Standard Error 1.19 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 | -20.00 Units on a scale | Standard Error 1.48 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -17.26 Units on a scale | Standard Error 1.37 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -5.58 Units on a scale | Standard Error 0.68 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -11.89 Units on a scale | Standard Error 1.4 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 6 | -13.53 Units on a scale | Standard Error 1.52 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -6.61 Units on a scale | Standard Error 0.89 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -11.10 Units on a scale | Standard Error 1.22 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -3.48 Units on a scale | Standard Error 0.68 |
| Placebo | Mean Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -8.95 Units on a scale | Standard Error 1.06 |
Comparison: 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.p-value: 0.0093Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.002295% CI: [-10.6, -2.35]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.144895% CI: [-7.23, 1.07]Mixed Models Analysis
Comparison: 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.p-value: 0.158895% CI: [-8.06, 1.32]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 1 | -0.11 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 2 | -0.31 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 3 | -0.63 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 4 | -0.67 Units on a scale | Standard Error 0.09 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 5 | -0.81 Units on a scale | Standard Error 0.1 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 6 | -0.91 Units on a scale | Standard Error 0.11 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 6 | -0.99 Units on a scale | Standard Error 0.09 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 4 | -0.72 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 1 | -0.16 Units on a scale | Standard Error 0.04 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 3 | -0.60 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 2 | -0.40 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 5 | -0.79 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 2 | -0.40 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 3 | -0.69 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 4 | -0.85 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 6 | -1.19 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 5 | -1.02 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 1 | -0.22 Units on a scale | Standard Error 0.04 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 5 | -0.68 Units on a scale | Standard Error 0.08 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 6 | -0.81 Units on a scale | Standard Error 0.09 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 2 | -0.36 Units on a scale | Standard Error 0.05 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 4 | -0.58 Units on a scale | Standard Error 0.07 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 1 | -0.12 Units on a scale | Standard Error 0.04 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression-Severity (CGI-S) Score. | Week 3 | -0.44 Units on a scale | Standard Error 0.06 |
Comparison: 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.p-value: 0.0069Mixed Models Analysis
Comparison: 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.p-value: 0.001595% CI: [-0.62, -0.15]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.126995% CI: [-0.42, -0.05]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.444995% CI: [-0.37, 0.16]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 1 | -0.35 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 2 | -0.76 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 3 | -1.21 Units on a scale | Standard Error 0.35 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 4 | -1.58 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 5 | -1.16 Units on a scale | Standard Error 0.42 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 6 | -1.94 Units on a scale | Standard Error 0.41 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 6 | -1.90 Units on a scale | Standard Error 0.33 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 4 | -1.52 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 3 | -1.31 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 5 | -1.48 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 2 | -1.31 Units on a scale | Standard Error 0.26 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 1 | -0.46 Units on a scale | Standard Error 0.21 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 2 | -1.21 Units on a scale | Standard Error 0.26 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 3 | -1.81 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 6 | -2.86 Units on a scale | Standard Error 0.33 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 4 | -2.12 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 5 | -2.27 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 1 | -1.01 Units on a scale | Standard Error 0.21 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 5 | -0.97 Units on a scale | Standard Error 0.35 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 3 | -0.82 Units on a scale | Standard Error 0.29 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 2 | -0.62 Units on a scale | Standard Error 0.26 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 1 | -0.48 Units on a scale | Standard Error 0.21 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 6 | -1.47 Units on a scale | Standard Error 0.34 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score. | Week 4 | -1.12 Units on a scale | Standard Error 0.3 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.002995% CI: [-2.3, -0.48]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.355995% CI: [-1.34, 0.48]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.364695% CI: [-1.51, 0.56]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 1 | -1.18 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 2 | -1.86 Units on a scale | Standard Error 0.27 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 3 | -2.43 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 4 | -2.85 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 5 | -2.93 Units on a scale | Standard Error 0.31 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 6 | -3.57 Units on a scale | Standard Error 0.3 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 6 | -3.62 Units on a scale | Standard Error 0.24 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 4 | -2.70 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 1 | -1.10 Units on a scale | Standard Error 0.18 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 3 | -2.10 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 2 | -1.91 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 5 | -2.87 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 2 | -1.60 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 3 | -2.24 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 4 | -2.93 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 6 | -3.78 Units on a scale | Standard Error 0.24 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 5 | -3.09 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 1 | -1.26 Units on a scale | Standard Error 0.18 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 5 | -2.69 Units on a scale | Standard Error 0.26 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 6 | -2.93 Units on a scale | Standard Error 0.24 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 2 | -1.47 Units on a scale | Standard Error 0.22 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 4 | -2.60 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 1 | -0.96 Units on a scale | Standard Error 0.18 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety and Depression Score. | Week 3 | -1.97 Units on a scale | Standard Error 0.23 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.010495% CI: [-1.51, -0.2]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.037395% CI: [-1.35, -0.04]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.08995% CI: [-1.39, 0.1]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 1 | -0.40 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 2 | -1.42 Units on a scale | Standard Error 0.27 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 3 | -2.35 Units on a scale | Standard Error 0.31 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 4 | -2.56 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 5 | -2.95 Units on a scale | Standard Error 0.41 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 6 | -3.46 Units on a scale | Standard Error 0.43 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 6 | -2.94 Units on a scale | Standard Error 0.35 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 4 | -2.27 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 1 | -0.46 Units on a scale | Standard Error 0.19 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 3 | -1.71 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 2 | -1.15 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 5 | -2.55 Units on a scale | Standard Error 0.33 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 2 | -1.37 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 3 | -2.32 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 4 | -2.83 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 6 | -3.98 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 5 | -3.42 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 1 | -0.78 Units on a scale | Standard Error 0.19 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 5 | -2.01 Units on a scale | Standard Error 0.33 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 6 | -2.59 Units on a scale | Standard Error 0.35 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 2 | -0.71 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 4 | -1.77 Units on a scale | Standard Error 0.3 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 1 | -0.42 Units on a scale | Standard Error 0.19 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thought Score. | Week 3 | -1.35 Units on a scale | Standard Error 0.26 |
Comparison: 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.p-value: 0.004595% CI: [-2.34, -0.43]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.475395% CI: [-1.31, 0.61]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.11595% CI: [-1.96, 0.21]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 1 | -0.70 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 2 | -1.71 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 3 | -2.55 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 4 | -3.21 Units on a scale | Standard Error 0.43 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 5 | -3.35 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 6 | -3.55 Units on a scale | Standard Error 0.48 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 6 | -3.53 Units on a scale | Standard Error 0.39 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 4 | -2.63 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 1 | -0.85 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 3 | -2.30 Units on a scale | Standard Error 0.3 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 2 | -1.86 Units on a scale | Standard Error 0.26 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 5 | -3.13 Units on a scale | Standard Error 0.38 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 2 | -1.72 Units on a scale | Standard Error 0.26 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 3 | -2.64 Units on a scale | Standard Error 0.3 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 4 | -3.17 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 6 | -3.84 Units on a scale | Standard Error 0.39 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 5 | -3.21 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 1 | -1.12 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 5 | -2.24 Units on a scale | Standard Error 0.38 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 6 | -2.55 Units on a scale | Standard Error 0.4 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 2 | -1.38 Units on a scale | Standard Error 0.26 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 4 | -2.16 Units on a scale | Standard Error 0.35 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 1 | -0.66 Units on a scale | Standard Error 0.22 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms Score. | Week 3 | -1.83 Units on a scale | Standard Error 0.3 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.019495% CI: [-2.36, -0.21]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.075495% CI: [-2.06, 0.1]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.10895% CI: [-2.22, 0.22]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 1 | -1.44 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 2 | -2.97 Units on a scale | Standard Error 0.39 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 3 | -4.48 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 4 | -5.42 Units on a scale | Standard Error 0.53 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 5 | -5.86 Units on a scale | Standard Error 0.58 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 6 | -6.56 Units on a scale | Standard Error 0.66 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 6 | -6.26 Units on a scale | Standard Error 0.53 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 4 | -4.93 Units on a scale | Standard Error 0.43 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 1 | -1.77 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 3 | -4.09 Units on a scale | Standard Error 0.38 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 2 | -3.10 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 5 | -5.35 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 2 | -3.03 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 3 | -4.39 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 4 | -5.48 Units on a scale | Standard Error 0.43 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 6 | -7.05 Units on a scale | Standard Error 0.53 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 5 | -6.41 Units on a scale | Standard Error 0.46 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 1 | -1.75 Units on a scale | Standard Error 0.24 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 5 | -5.47 Units on a scale | Standard Error 0.47 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 6 | -5.91 Units on a scale | Standard Error 0.54 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 2 | -3.03 Units on a scale | Standard Error 0.32 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 4 | -4.67 Units on a scale | Standard Error 0.44 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 1 | -1.30 Units on a scale | Standard Error 0.24 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms Score. | Week 3 | -3.78 Units on a scale | Standard Error 0.38 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.127395% CI: [-2.61, 0.33]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.6495% CI: [-1.83, 1.12]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.442395% CI: [-2.32, 1.01]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 1 | 0.03 Units on a scale | Standard Error 0.22 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 2 | -0.15 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 3 | -0.46 Units on a scale | Standard Error 0.3 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 4 | -0.74 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 5 | -0.34 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 6 | -0.90 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 6 | -0.81 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 4 | -0.74 Units on a scale | Standard Error 0.26 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 1 | -0.10 Units on a scale | Standard Error 0.18 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 3 | -0.61 Units on a scale | Standard Error 0.24 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 2 | -0.65 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 5 | -0.60 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 2 | -0.68 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 3 | -1.16 Units on a scale | Standard Error 0.24 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 4 | -1.31 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 6 | -1.89 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 5 | -1.50 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 1 | -0.63 Units on a scale | Standard Error 0.18 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 5 | -0.22 Units on a scale | Standard Error 0.3 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 6 | -0.64 Units on a scale | Standard Error 0.3 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 2 | -0.13 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 4 | -0.39 Units on a scale | Standard Error 0.26 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 1 | -0.21 Units on a scale | Standard Error 0.18 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility and Excitement Score. | Week 3 | -0.19 Units on a scale | Standard Error 0.24 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.002195% CI: [-2.05, -0.46]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.679295% CI: [-0.97, 0.63]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.575295% CI: [-1.16, 0.65]Mixed Models Analysis
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 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: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 1 | -0.31 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 2 | -1.27 Units on a scale | Standard Error 0.29 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 3 | -2.06 Units on a scale | Standard Error 0.35 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 4 | -2.56 Units on a scale | Standard Error 0.4 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 5 | -2.71 Units on a scale | Standard Error 0.44 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 6 | -2.92 Units on a scale | Standard Error 0.48 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 6 | -2.91 Units on a scale | Standard Error 0.38 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 4 | -2.09 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 1 | -0.52 Units on a scale | Standard Error 0.2 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 3 | -1.80 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 2 | -1.31 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 5 | -2.50 Units on a scale | Standard Error 0.35 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 2 | -1.42 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 3 | -2.15 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 4 | -2.69 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 6 | -3.36 Units on a scale | Standard Error 0.38 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 5 | -2.82 Units on a scale | Standard Error 0.35 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 1 | -0.88 Units on a scale | Standard Error 0.2 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 5 | -1.74 Units on a scale | Standard Error 0.36 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 6 | -2.14 Units on a scale | Standard Error 0.39 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 2 | -0.79 Units on a scale | Standard Error 0.24 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 4 | -1.67 Units on a scale | Standard Error 0.33 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 1 | -0.40 Units on a scale | Standard Error 0.2 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score. | Week 3 | -1.18 Units on a scale | Standard Error 0.28 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.023195% CI: [-2.28, -0.17]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.154795% CI: [-1.83, 0.29]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.200495% CI: [-1.98, 0.42]Mixed Models Analysis
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/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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 1 | -0.93 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 3 | -3.94 Units on a scale | Standard Error 0.46 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 5 | -4.80 Units on a scale | Standard Error 0.58 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 2 | -2.54 Units on a scale | Standard Error 0.39 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 6 | -5.63 Units on a scale | Standard Error 0.62 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 4 | -4.83 Units on a scale | Standard Error 0.52 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 1 | -1.43 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 2 | -2.76 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 3 | -3.56 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 4 | -4.35 Units on a scale | Standard Error 0.42 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 5 | -4.68 Units on a scale | Standard Error 0.47 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 6 | -5.42 Units on a scale | Standard Error 0.5 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 2 | -2.93 Units on a scale | Standard Error 0.32 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 4 | -5.16 Units on a scale | Standard Error 0.41 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 6 | -6.65 Units on a scale | Standard Error 0.5 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 5 | -6.04 Units on a scale | Standard Error 0.46 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 1 | -1.80 Units on a scale | Standard Error 0.23 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 3 | -4.43 Units on a scale | Standard Error 0.37 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 6 | -4.95 Units on a scale | Standard Error 0.51 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 2 | -2.56 Units on a scale | Standard Error 0.32 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 5 | -4.33 Units on a scale | Standard Error 0.47 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 4 | -3.93 Units on a scale | Standard Error 0.42 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 1 | -1.25 Units on a scale | Standard Error 0.23 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score. | Week 3 | -3.34 Units on a scale | Standard Error 0.37 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.016695% CI: [-3.08, -0.31]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.510195% CI: [-1.86, 0.93]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.393895% CI: [-2.26, 0.89]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score.
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 3 | 6.97 Units on a scale | Standard Error 0.9 |
| Brexpiprazole 1 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 6 | 11.73 Units on a scale | Standard Error 1.19 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 6 | 10.52 Units on a scale | Standard Error 0.95 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 3 | 6.85 Units on a scale | Standard Error 0.73 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 3 | 7.12 Units on a scale | Standard Error 0.71 |
| Brexpiprazole 4 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 6 | 13.11 Units on a scale | Standard Error 0.94 |
| Placebo | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 3 | 5.80 Units on a scale | Standard Error 0.73 |
| Placebo | Mean Change From Baseline to Week 6 in Personal and Social Performance (PSP) Score. | Week 6 | 8.52 Units on a scale | Standard Error 0.97 |
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.128695% CI: [-0.58, 4.59]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.000595% CI: [2.02, 7.17]Mixed Models Analysis
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.033295% CI: [0.26, 6.16]Mixed Models Analysis
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: Week 6
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 1 mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | 3.20 Units on a scale | Standard Deviation 1.45 |
| Brexpiprazole 2 mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | 3.17 Units on a scale | Standard Deviation 1.34 |
| Brexpiprazole 4 mg | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | 2.95 Units on a scale | Standard Deviation 1.33 |
| Placebo | Mean Clinical Global Impression-Improvement (CGI-I) Scale Score at Week 6. | 3.48 Units on a scale | Standard Deviation 1.46 |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.000995% CI: [-0.78, -0.2]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.042295% CI: [-0.6, -0.01]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.135895% CI: [-0.56, 0.08]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6.
Participants discontinued for lack of efficacy during the trial were reported here.
Time frame: Week 6
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 1 mg | Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. | 7.69 percentage of participants |
| Brexpiprazole 2 mg | Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. | 11.2 percentage of participants |
| Brexpiprazole 4 mg | Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. | 8.84 percentage of participants |
| Placebo | Percentage of Participants With Discontinuation Rate for Lack of Efficacy at Week 6. | 11.7 percentage of participants |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.520295% CI: [0.44, 1.51]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.989495% CI: [0.55, 1.85]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.458695% CI: [0.36, 1.59]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Response at Week 6.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Brexpiprazole 1 mg | Percentage of Participants With Response at Week 6. | 43.6 percentage of participants |
| Brexpiprazole 2 mg | Percentage of Participants With Response at Week 6. | 38.5 percentage of participants |
| Brexpiprazole 4 mg | Percentage of Participants With Response at Week 6. | 49.7 percentage of participants |
| Placebo | Percentage of Participants With Response at Week 6. | 31.7 percentage of participants |
Comparison: Statistical analysis to compare brexpiprazole 4mg/day and placebo was performed at Week 6.p-value: 0.000695% CI: [1.2, 2]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 2mg/day and placebo was performed at Week 6.p-value: 0.16895% CI: [0.92, 1.62]Cochran-Mantel-Haenszel
Comparison: Statistical analysis to compare brexpiprazole 1mg/day and placebo was performed at Week 6.p-value: 0.043395% CI: [1.02, 1.79]Cochran-Mantel-Haenszel