Schizophrenia
Conditions
Brief summary
To determine the efficacy and safety of brexpiprazole for the treatment of adults experiencing an acute episode of schizophrenia.
Interventions
DRUGPlacebo
Once daily as tablets and capsules, orally
DRUGBrexpiprazole
2-4 mg/day, once daily, tablets, orally
400-800 mg/day, once daily, encapsulated tablets, orally
Sponsors
Otsuka Pharmaceutical Co., Ltd.
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* The patient has schizophrenia, diagnosed according to DSM-IV-TR™ and confirmed by the Mini International Neuropsychiatric Interview (MINI). * The patient has an acute exacerbation of psychotic symptoms and marked deterioration of usual function. * The patient is willing to be hospitalised from the Screening Visit through Week 6. * The patient will benefit from hospitalisation or continued hospitalisation for treatment of a current acute relapse of schizophrenia at study entry. * The patient has a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding the current episode. * The patient agrees to protocol-defined use of effective contraception.
Exclusion criteria
* The patient has a current Axis I diagnosis (DSM-IV-TR™ criteria) other than schizophrenia established as primary diagnosis. * The patient suffers from a current Axis II diagnosis (DSM-IV-TR™ criteria). * The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria). * The patient, in the opinion of the investigator or according to Columbia Suicide Severity Rating Scale (C-SSRS), is at significant risk of suicide. * The patient has clinically significant tardive dyskinesia or severe akathisia at enrolment. * The patient has a history of neuroleptic malignant syndrome. * The patient has any relevant medical history or current presence of systemic disease. * The patient has, at the Screening Visit an abnormal ECG or other abnormal ECG tests that are, in the investigator's opinion, clinically significant. * The patient has a history of cancer, other than basal cell or Stage 1 squamous cell carcinoma of the skin, that has not been in remission for \>5 years prior to the first dose of brexpiprazole. * The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason. Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in PANSS Total Score | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGI-I Score at Week 6 | Week 6 | The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not. |
| Change From Baseline to Week 6 in PANSS Positive Subscale Score | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Positive Subscale score is calculated from 7 items (for example: delusions, conceptual disorganization and hallucinatory behaviour). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS Negative Subscale Score | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Negative Subscale score is calculated from 7 items (for example: blunted affect, emotional withdrawal and poor rapport). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS General Psychopathology Subscale score is calculated from 16 items (for example: somatic concern, anxiety and guilt feelings). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS Excited Component Score | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Excited Component score is calculated from 5 items (for example: poor impulse control, tension and hostility). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: negative symptoms is calculated from 7 items (for example: blunted affect, emotional withdrawal and motor retardation). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: positive symptoms is calculated from 8 items (for example: delusions, conceptual disorganization and stereotype thinking). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: disorganized thoughts is calculated from 7 items (for example: conceptual disorganization, difficulty in abstract thinking and mannerisms and posturing). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Change From Baseline to Week 6 in CGI-S Score | Baseline and Week 6 | The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). |
| Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: anxiety/depression is calculated from 4 items (for example: anxiety, guilt feelings, and tension). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
| Discontinuation Due to Lack of Efficacy During the Study | Baseline to Week 6 | Discontinuation due to lack of efficacy was based on the primary reason for withdrawal |
| Response Rate at Week 6 | Baseline and Week 6 | The response rate was defined as a reduction of ≥30% from baseline in PANSS total score OR a CGI-I score of 1 or 2 |
| Change From Baseline to Week 6 in PSP Total Score | Baseline and Week 6 | The Personal and Social Performance Scale (PSP) is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. The PSP scale consists of a 100-point single-item rating scale, subdivided into 10 equal intervals. Scores of 1 to 10 indicate lack of autonomy in basic functioning, whereas scores of 91 to 100 reflect excellent functioning. The total score is rated by the investigator and is based on an algorithm which takes both the ratings of the 4 primary domains of PSP, and the combination of these ratings into account. The 4 primary domains are: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 domains are assessed on a 6-point scale, from absent to very severe. A higher score indicates a better performance. |
| PSP Functional Remission Rate at Week 6 | Week 6 | The PSP functional remission rate was defined as a PSP total score ≥71 |
| PSP Functional Response Rate at Week 6 | Week 6 | The PSP functional response rate was defined as ≥10 point improvement from Baseline on the PSP total score |
| PSP Domain D: Disturbing and Aggressive Behaviours at Week 6 | Week 6 | PSP domain D: disturbing and aggressive behaviours were categorised as aggressive (corresponding to mild, manifest, marked, severe, or very severe) or nonaggressive (corresponding to absent) |
| Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement | Baseline and Week 6 | The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: uncontrolled hostility/excitement is calculated from 4 items (for example: excitement, hostility, and uncooperativeness).Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo: Once daily as tablets and capsules, orally | 161 |
| Brexpiprazole Brexpiprazole: 2-4 mg/day, once daily, tablets, orally | 150 |
| Quetiapine Extended Release Active Reference
Quetiapine extended release: 400-800 mg/day, once daily, encapsulated tablets, orally | 153 |
| Total | 464 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative or other reasons | 11 | 13 | 9 |
| Overall Study | Adverse Event | 11 | 14 | 4 |
| Overall Study | Lack of Efficacy | 24 | 10 | 11 |
| Overall Study | Protocol Violation | 1 | 0 | 1 |
| Overall Study | Randomised not treated | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 0 | 6 |
Baseline characteristics
| Characteristic | Placebo | Total | Quetiapine Extended Release | Brexpiprazole |
|---|---|---|---|---|
| Age, Continuous | 40.85 years STANDARD_DEVIATION 10.56 | 40.56 years STANDARD_DEVIATION 10.77 | 41.12 years STANDARD_DEVIATION 10.91 | 39.68 years STANDARD_DEVIATION 10.87 |
| CGI-S Score | 4.94 units on a scale STANDARD_DEVIATION 0.57 | 4.96 units on a scale STANDARD_DEVIATION 0.58 | 4.98 units on a scale STANDARD_DEVIATION 0.57 | 4.96 units on a scale STANDARD_DEVIATION 0.59 |
| PANSS total score | 98.38 units on a scale STANDARD_DEVIATION 10.3 | 98.34 units on a scale STANDARD_DEVIATION 10.45 | 98.82 units on a scale STANDARD_DEVIATION 10.83 | 97.82 units on a scale STANDARD_DEVIATION 10.25 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 106 Participants | 38 Participants | 33 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 123 Participants | 349 Participants | 113 Participants | 113 Participants |
| Region of Enrollment Estonia | 4 participants | 11 participants | 4 participants | 3 participants |
| Region of Enrollment France | 1 participants | 2 participants | 1 participants | 0 participants |
| Region of Enrollment Poland | 5 participants | 15 participants | 5 participants | 5 participants |
| Region of Enrollment Romania | 14 participants | 38 participants | 11 participants | 13 participants |
| Region of Enrollment Russian Federation | 43 participants | 115 participants | 35 participants | 37 participants |
| Region of Enrollment Serbia | 13 participants | 35 participants | 11 participants | 11 participants |
| Region of Enrollment Slovakia | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment Ukraine | 30 participants | 87 participants | 29 participants | 28 participants |
| Region of Enrollment United States | 50 participants | 158 participants | 56 participants | 52 participants |
| Sex: Female, Male Female | 70 Participants | 200 Participants | 64 Participants | 66 Participants |
| Sex: Female, Male Male | 91 Participants | 264 Participants | 89 Participants | 84 Participants |
| Time since first antipsychotic treatment (years) | 14.48 years STANDARD_DEVIATION 8.98 | 14.08 years STANDARD_DEVIATION 9.16 | 14.31 years STANDARD_DEVIATION 9.34 | 13.43 years STANDARD_DEVIATION 9.19 |
| Time since schizophrenia diagnosis (years) | 14.15 years STANDARD_DEVIATION 9.35 | 13.62 years STANDARD_DEVIATION 9.42 | 13.78 years STANDARD_DEVIATION 9.49 | 12.88 years STANDARD_DEVIATION 9.43 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 161 | 48 / 150 | 73 / 153 |
| serious Total, serious adverse events | 6 / 161 | 7 / 150 | 2 / 153 |
Outcome results
Primary
Change From Baseline to Week 6 in PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a 30-item scale for assessing the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranged from 30 to 210 with a higher score indicating greater severity of symptoms.
Time frame: Baseline and Week 6
Population: Full-analysis set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Total Score | -15.9 units on a scale | Standard Error 1.5 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Total Score | -20.0 units on a scale | Standard Error 1.5 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Total Score | -24.0 units on a scale | Standard Error 1.5 |
Comparison: The overall significance level was 0.05. The primary and the key secondary endpoints were tested hierarchically. Only if the primary endpoint was statistically significant would confirmatory testing continue with the key secondary endpoint.p-value: 0.05695% CI: [-8.2, 0.1]Mixed Models Analysis
p-value: 0.000295% CI: [-12.2, -3.9]Mixed Models Analysis
Secondary
CGI-I Score at Week 6
The Clinical Global Impression - Global Improvement (CGI-I) provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.
Time frame: Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CGI-I Score at Week 6 | 3.0 units on a scale | Standard Error 0.1 |
| Brexpiprazole | CGI-I Score at Week 6 | 2.7 units on a scale | Standard Error 0.1 |
| Quetiapine Extended Release | CGI-I Score at Week 6 | 2.5 units on a scale | Standard Error 0.1 |
Secondary
Change From Baseline to Week 6 in CGI-S Score
The Clinical Global Impression - Severity of Illness (CGI-S) provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in CGI-S Score | -0.9 units on a scale | Standard Error 0.1 |
| Brexpiprazole | Change From Baseline to Week 6 in CGI-S Score | -1.2 units on a scale | Standard Error 0.1 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in CGI-S Score | -1.4 units on a scale | Standard Error 0.1 |
Secondary
Change From Baseline to Week 6 in PANSS Excited Component Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Excited Component score is calculated from 5 items (for example: poor impulse control, tension and hostility). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Excited Component Score | -2.5 units on a scale | Standard Error 0.3 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Excited Component Score | -3.3 units on a scale | Standard Error 0.3 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Excited Component Score | -3.9 units on a scale | Standard Error 0.3 |
Secondary
Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS General Psychopathology Subscale score is calculated from 16 items (for example: somatic concern, anxiety and guilt feelings). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score | -8.2 units on a scale | Standard Error 0.7 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score | -9.9 units on a scale | Standard Error 0.7 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS General Psychopathology Subscale Score | -11.6 units on a scale | Standard Error 0.7 |
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: anxiety/depression is calculated from 4 items (for example: anxiety, guilt feelings, and tension). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression | -2.9 units on a scale | Standard Error 0.2 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression | -3.2 units on a scale | Standard Error 0.2 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Anxiety/Depression | -3.6 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: disorganized thoughts is calculated from 7 items (for example: conceptual disorganization, difficulty in abstract thinking and mannerisms and posturing). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts | -3.2 units on a scale | Standard Error 0.4 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts | -4.0 units on a scale | Standard Error 0.4 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Disorganized Thoughts | -4.8 units on a scale | Standard Error 0.3 |
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: negative symptoms is calculated from 7 items (for example: blunted affect, emotional withdrawal and motor retardation). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms | -3.6 units on a scale | Standard Error 0.4 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms | -4.3 units on a scale | Standard Error 0.4 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Negative Symptoms | -4.8 units on a scale | Standard Error 0.4 |
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: positive symptoms is calculated from 8 items (for example: delusions, conceptual disorganization and stereotype thinking). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms | -5.7 units on a scale | Standard Error 0.5 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms | -7.1 units on a scale | Standard Error 0.5 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Positive Symptoms | -8.4 units on a scale | Standard Error 0.5 |
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Marder Factor scores: uncontrolled hostility/excitement is calculated from 4 items (for example: excitement, hostility, and uncooperativeness).Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement | -1.8 units on a scale | Standard Error 0.3 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement | -2.5 units on a scale | Standard Error 0.3 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement | -2.8 units on a scale | Standard Error 0.3 |
Secondary
Change From Baseline to Week 6 in PANSS Negative Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Negative Subscale score is calculated from 7 items (for example: blunted affect, emotional withdrawal and poor rapport). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Negative Subscale Score | -3.1 units on a scale | Standard Error 0.4 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Negative Subscale Score | -3.7 units on a scale | Standard Error 0.4 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Negative Subscale Score | -4.5 units on a scale | Standard Error 0.4 |
Secondary
Change From Baseline to Week 6 in PANSS Positive Subscale Score
The Positive and Negative Syndrome Scale (PANSS) is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS Positive Subscale score is calculated from 7 items (for example: delusions, conceptual disorganization and hallucinatory behaviour). Symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. Higher score indicating greater severity of symptoms
Time frame: Baseline and Week 6
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PANSS Positive Subscale Score | -5.4 units on a scale | Standard Error 0.5 |
| Brexpiprazole | Change From Baseline to Week 6 in PANSS Positive Subscale Score | -7.0 units on a scale | Standard Error 0.5 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PANSS Positive Subscale Score | -8.1 units on a scale | Standard Error 0.5 |
Secondary
Change From Baseline to Week 6 in PSP Total Score
The Personal and Social Performance Scale (PSP) is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. The PSP scale consists of a 100-point single-item rating scale, subdivided into 10 equal intervals. Scores of 1 to 10 indicate lack of autonomy in basic functioning, whereas scores of 91 to 100 reflect excellent functioning. The total score is rated by the investigator and is based on an algorithm which takes both the ratings of the 4 primary domains of PSP, and the combination of these ratings into account. The 4 primary domains are: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 domains are assessed on a 6-point scale, from absent to very severe. A higher score indicates a better performance.
Time frame: Baseline and Week 6
Population: FAS. PSP was collected at Baseline, Day 21 and Day 42 only, due to the windowing only patients with PSP assessments between Days 15 to 27 and after Day 35 were included in this analysis; the number of participants analysed is therefore smaller than the defined FAS and also smaller than other PSP analyses using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 6 in PSP Total Score | 9.4 units on a scale | Standard Error 1 |
| Brexpiprazole | Change From Baseline to Week 6 in PSP Total Score | 13.0 units on a scale | Standard Error 1 |
| Quetiapine Extended Release | Change From Baseline to Week 6 in PSP Total Score | 15.3 units on a scale | Standard Error 1 |
Secondary
Discontinuation Due to Lack of Efficacy During the Study
Discontinuation due to lack of efficacy was based on the primary reason for withdrawal
Time frame: Baseline to Week 6
Population: APTS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Discontinuation Due to Lack of Efficacy During the Study | 14.91 percentage of patients |
| Brexpiprazole | Discontinuation Due to Lack of Efficacy During the Study | 6.67 percentage of patients |
| Quetiapine Extended Release | Discontinuation Due to Lack of Efficacy During the Study | 7.19 percentage of patients |
Secondary
PSP Domain D: Disturbing and Aggressive Behaviours at Week 6
PSP domain D: disturbing and aggressive behaviours were categorised as aggressive (corresponding to mild, manifest, marked, severe, or very severe) or nonaggressive (corresponding to absent)
Time frame: Week 6
Population: FAS. As this was based on observed cases, only patients who have PSP assessment at Week 6 were included in this analysis; the number of participants analysed is therefore smaller than the defined FAS and also smaller than other PSP analyses where last assessment carried forward was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | PSP Domain D: Disturbing and Aggressive Behaviours at Week 6 | 30.4 percentage of aggressive patients |
| Brexpiprazole | PSP Domain D: Disturbing and Aggressive Behaviours at Week 6 | 27.2 percentage of aggressive patients |
| Quetiapine Extended Release | PSP Domain D: Disturbing and Aggressive Behaviours at Week 6 | 22.2 percentage of aggressive patients |
Secondary
PSP Functional Remission Rate at Week 6
The PSP functional remission rate was defined as a PSP total score ≥71
Time frame: Week 6
Population: FAS (last assessment). Patients who have no post-baseline PSP values available were not included as response is defined based on change from baseline and no baseline carried forward analysis was planned; the number of participants analysed is therefore smaller than the defined FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | PSP Functional Remission Rate at Week 6 | 5.7 percentage of remitters |
| Brexpiprazole | PSP Functional Remission Rate at Week 6 | 9.6 percentage of remitters |
| Quetiapine Extended Release | PSP Functional Remission Rate at Week 6 | 14.4 percentage of remitters |
Secondary
PSP Functional Response Rate at Week 6
The PSP functional response rate was defined as ≥10 point improvement from Baseline on the PSP total score
Time frame: Week 6
Population: FAS (last assessment). Patients who have no post-baseline PSP values available were not included as response is defined based on change from baseline and no baseline carried forward analysis was planned; the number of participants analysed is therefore smaller than the defined FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | PSP Functional Response Rate at Week 6 | 36.3 percentage of responders |
| Brexpiprazole | PSP Functional Response Rate at Week 6 | 53.4 percentage of responders |
| Quetiapine Extended Release | PSP Functional Response Rate at Week 6 | 64.4 percentage of responders |
Secondary
Response Rate at Week 6
The response rate was defined as a reduction of ≥30% from baseline in PANSS total score OR a CGI-I score of 1 or 2
Time frame: Baseline and Week 6
Population: FAS (last assessment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Response Rate at Week 6 | 32.1 percentage of responders |
| Brexpiprazole | Response Rate at Week 6 | 48.7 percentage of responders |
| Quetiapine Extended Release | Response Rate at Week 6 | 62.7 percentage of responders |