Acute Schizophrenia
Conditions
Brief summary
The purpose of this study is to compare the effectiveness, safety and tolerability of three different doses of OPC-34712 with placebo in the treatment of acute schizophrenia in adults.
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 [Brexpiprazole] High Dose
Higher dose, tablet, once daily, for six weeks
DRUGExperimental: OPC-34712 [Brexpiprazole] Middle Dose
Middle dose, tablet, once daily, for six weeks
DRUGExperimental: OPC-34712 [Brexpiprazole] Low Dose
Lower 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 the Diagnostic and Statistical Manual of Mental Disorders (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 * Major depressive 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 Positive and Negative Syndrome Scale (PANSS) Total Score. | Baseline to Week 6 | The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. 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 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Baseline to Week 1, 2, 3, 4, 5 | The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome). |
| Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Baseline to Week 1, 2, 3, 4 and 5 | The severity of illness was rated using the CGI-S. To perform this assessment, the rater or 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 participant. |
| Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) | Baseline to Week 6 | The PSP is a clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (eg, 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 to Week 6 | For each symptom construct of the PANSS Positive Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. |
| Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score | Baseline to Week 6 | For each symptom construct of the PANSS Negative Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. |
| Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 | Week 6 | The participant's overall improvement was rated using the CGI-I. The rater or study physician rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared with the participant's condition at screening/baseline. Response choices were: 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. |
| Response Rate at Week 6 | Week 6 | Response rate was defined as improvement in mean change of ≥30% from baseline in PANSS Total Score at Week 6 or CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6. |
| Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Baseline to Week 6 | The severity of illness was rated using the CGI-S which is the key secondary endpoint. To perform this assessment, the rater or 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 participant. |
| Discontinuation Rate for Lack of Efficacy at Week 6 | Week 6 | — |
| Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score | Baseline to Week 6 | The PANSS Marder Factor score - Positive Symptoms Score consists of 8 PANSS items (delusions \[P1\], hallucinatory behaviour \[P3\], grandiosity \[P5\], suspiciousness \[P6\], stereotyped thinking \[N7\], somatic concern \[G1\], unusual thought content \[G9\], lack of judgment and insight \[G10\]. Each was rated on a scale of 1 (absent) to 7 (extreme). The PANSS Marder Factor score - Positive Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 8 items, and ranged from 8 to 42 with a higher score indicating greater severity of symptoms. |
| Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score | Baseline to Week 6 | The PANSS Marder Factor score - Negative Symptoms Score consists of 7 PANSS items (blunted effect \[N1\], emotional withdrawal \[N2\], poor rapport \[N3\], passive/apathetic social withdrawal \[N4\], lack of spontaneity and conversation flow \[N6\], motor retardation \[G7\], active social avoidance \[G16\]). The PANSS Marder Factor score - Negative Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. |
| Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score | Baseline to Week 6 | The PANSS Marder Factor score -Disorganized Thought Score consists of 7 PANSS items (conceptual disorganization \[P2\], difficulty in abstract thinking \[N5\], mannerisms and posturing \[G5\], disorientation \[G10\], poor attention \[G11\], disturbance of violation \[G13\], preoccupation \[G15\]). The PANSS Marder Factor score - Disorganized Thought Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms. |
| Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score | Baseline to Week 6 | The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score consists of 4 PANSS items (excitement \[P4\], hostility \[P7\], uncooperativeness \[G8\], poor impulse control \[G14\]). The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. |
| Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score | Baseline to Week 6 | The PANSS Marder Factor score - Anxiety/Depression Score consists of 4 PANSS items (anxiety \[G2\], guilt feelings \[G3\], tension \[G4\], depression \[G6\]). The PANSS Marder Factor score - Anxiety/Depression Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms. |
| Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score | Baseline to Week 6 | The PEC consists of 5 PANSS items (excitement \[P4\], hostility \[P7\], tension \[G4\], uncooperativeness \[G8\], and poor impulse control \[G14\]). Each rated on a scale of 1 (absent) to 7 (extreme). The PEC for participants was calculated as the sum of the rating assigned to each of the 5 items, and ranged from 5 to 35 with a higher score indicating greater severity of symptoms. |
Countries
Canada, Japan, Latvia, Poland, Romania, Serbia, South Korea, Ukraine, United States
Participant flow
Recruitment details
The trial was conducted in 636 participants from 65 trial sites in 10 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 for schizophrenia and psychotic disorders studies.
Participants by arm
| Arm | Count |
|---|---|
| Brexpiprazole 4mg Brexpiprazole 4mg tablet once daily for 6 weeks.
Participants were titrated to the target dose of brexpiprazole over a 1-week period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose the day after the Week 1 visit (ie, the beginning of Week 2). | 180 |
| Brexpiprazole 2mg Brexpiprazole 2mg tablet once daily for 6 weeks.
Participants were titrated to the target dose of brexpiprazole over a 5 day period beginning at the randomization (Day 1), and all participants were to have achieved the assigned dose by Day 5. | 182 |
| Brexpiprazole 0.25 mg Brexpiprazole 0.25mg tablet once daily for 6 weeks. | 90 |
| Placebo Placebo tablet once daily for 6 weeks. | 184 |
| Total | 636 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 17 | 15 | 12 | 32 |
| Overall Study | Lack of Efficacy | 7 | 17 | 7 | 18 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Participant Met Withdrawal Criteria | 1 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 0 | 3 |
| Overall Study | Protocol Deviation | 2 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 31 | 24 | 13 | 21 |
Baseline characteristics
| Characteristic | Brexpiprazole 4mg | Brexpiprazole 2mg | Brexpiprazole 0.25 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.8 Years STANDARD_DEVIATION 11 | 39.6 Years STANDARD_DEVIATION 10.2 | 40.5 Years STANDARD_DEVIATION 11.4 | 39.7 Years STANDARD_DEVIATION 10.8 | 40.1 Years STANDARD_DEVIATION 10.8 |
| Sex: Female, Male Female | 69 Participants | 71 Participants | 29 Participants | 66 Participants | 235 Participants |
| Sex: Female, Male Male | 111 Participants | 111 Participants | 61 Participants | 118 Participants | 401 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 | 64 / 180 | 53 / 182 | 25 / 90 | 65 / 184 |
| serious Total, serious adverse events | 2 / 180 | 4 / 182 | 4 / 90 | 7 / 184 |
Outcome results
Primary
Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 134, 132, 62 and 124 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score. | -19.65 Units on a scale | Standard Error 1.54 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score. | -20.73 Units on a scale | Standard Error 1.55 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score. | -14.90 Units on a scale | Standard Error 2.23 |
| Placebo | Mean Change From Baseline to Week 6 Positive and Negative Syndrome Scale (PANSS) Total Score. | -12.01 Units on a scale | Standard Error 1.6 |
Comparison: Difference between average effect of brexpiprazole 2 and 4 mg/day and placebo was tested first at alpha level of 0.05. If statistically significant, then comparisons for each group (brexpiprazole 2 and 4 mg/day) versus placebo were performed.p-value: <0.000195% CI: [-12, -4.4]Mixed Models Analysis
Comparison: Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of -7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-testp-value: 0.000695% CI: [-12, -3.3]Mixed Models Analysis
Comparison: Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of -7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-testp-value: <0.000195% CI: [-13.1, -4.37]Mixed Models Analysis
Comparison: Sample size was determined to achieve 90% power at alpha level of 0.025 (two-sided) to a detect treatment difference of -7.5 points in change from baseline in PANSS Total Score at Week 6 (last observation carried forward) between a brexpiprazole treatment of 4 mg/day (or 2 mg/day) and placebo using a two-sided z-testp-value: 0.29195% CI: [-8.27, 2.49]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score
The PANSS Marder Factor score - Anxiety/Depression Score consists of 4 PANSS items (anxiety \[G2\], guilt feelings \[G3\], tension \[G4\], depression \[G6\]). The PANSS Marder Factor score - Anxiety/Depression Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score | -3.40 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 2 mg | Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score | -3.70 Units on a scale | Standard Error 0.25 |
| Brexpiprazole 0.25 mg | Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score | -3.27 Units on a scale | Standard Error 0.35 |
| Placebo | Change From Baseline to Week 6 in PANSS Marder Anxiety Depression Score | -3.05 Units on a scale | Standard Error 0.26 |
p-value: 0.328495% CI: [-1.03, 0.35]Mixed Models Analysis
p-value: 0.065595% CI: [-1.34, 0.04]Mixed Models Analysis
p-value: 0.625195% CI: [-1.07, 0.64]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score
The PANSS Marder Factor score -Disorganized Thought Score consists of 7 PANSS items (conceptual disorganization \[P2\], difficulty in abstract thinking \[N5\], mannerisms and posturing \[G5\], disorientation \[G10\], poor attention \[G11\], disturbance of violation \[G13\], preoccupation \[G15\]). The PANSS Marder Factor score - Disorganized Thought Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score | -3.72 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 2 mg | Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score | -3.94 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 0.25 mg | Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score | -2.69 Units on a scale | Standard Error 0.52 |
| Placebo | Change From Baseline to Week 6 in PANSS Marder Disorganised Thought Score | -1.97 Units on a scale | Standard Error 0.37 |
p-value: 0.000795% CI: [-2.76, -0.75]Mixed Models Analysis
p-value: 0.000195% CI: [-2.98, -0.97]Mixed Models Analysis
p-value: 0.257295% CI: [-1.96, 0.52]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score
The PANSS Marder Factor score - Negative Symptoms Score consists of 7 PANSS items (blunted effect \[N1\], emotional withdrawal \[N2\], poor rapport \[N3\], passive/apathetic social withdrawal \[N4\], lack of spontaneity and conversation flow \[N6\], motor retardation \[G7\], active social avoidance \[G16\]). The PANSS Marder Factor score - Negative Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 7 items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score | -4.10 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 2 mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score | -4.48 Units on a scale | Standard Error 0.37 |
| Brexpiprazole 0.25 mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score | -3.66 Units on a scale | Standard Error 0.54 |
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Score - Negative Symptoms Score | -2.80 Units on a scale | Standard Error 0.38 |
p-value: 0.015595% CI: [-2.35, -0.25]Mixed Models Analysis
p-value: 0.001995% CI: [-2.73, -0.62]Mixed Models Analysis
p-value: 0.195695% CI: [-2.17, 0.44]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score
The PANSS Marder Factor score - Positive Symptoms Score consists of 8 PANSS items (delusions \[P1\], hallucinatory behaviour \[P3\], grandiosity \[P5\], suspiciousness \[P6\], stereotyped thinking \[N7\], somatic concern \[G1\], unusual thought content \[G9\], lack of judgment and insight \[G10\]. Each was rated on a scale of 1 (absent) to 7 (extreme). The PANSS Marder Factor score - Positive Symptoms Score for participants was calculated as the sum of the rating assigned to each of the 8 items, and ranged from 8 to 42 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score | -7.23 Units on a scale | Standard Error 0.51 |
| Brexpiprazole 2 mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score | -7.37 Units on a scale | Standard Error 0.51 |
| Brexpiprazole 0.25 mg | Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score | -5.78 Units on a scale | Standard Error 0.73 |
| Placebo | Change From Baseline to Week 6 in PANSS Marder Factor Score - Positive Symptoms Score | -4.89 Units on a scale | Standard Error 0.53 |
p-value: 0.001495% CI: [-3.77, -0.91]Mixed Models Analysis
p-value: 0.000895% CI: [-3.91, -1.04]Mixed Models Analysis
p-value: 0.326395% CI: [-2.66, 0.89]Mixed Models Analysis
Secondary
Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score
The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score consists of 4 PANSS items (excitement \[P4\], hostility \[P7\], uncooperativeness \[G8\], poor impulse control \[G14\]). The PANSS Marder Factor score - Uncontrolled Hostility/Excitement Score for participants was calculated as the sum of the rating assigned to each of the 4 items, and ranged from 4 to 28 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score | -1.90 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 2 mg | Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score | -1.91 Units on a scale | Standard Error 0.28 |
| Brexpiprazole 0.25 mg | Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score | -1.15 Units on a scale | Standard Error 0.41 |
| Placebo | Change From Baseline to Week 6 in PANSS Marder Uncontrolled Hostility/Excitement Score | -0.82 Units on a scale | Standard Error 0.3 |
p-value: 0.008595% CI: [-1.87, -0.28]Mixed Models Analysis
p-value: 0.008195% CI: [-1.88, -0.28]Mixed Models Analysis
p-value: 0.517295% CI: [-1.31, 0.66]Mixed Models Analysis
Secondary
Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6
The participant's overall improvement was rated using the CGI-I. The rater or study physician rated the participant's total improvement whether or not it was due entirely to drug treatment. All responses were compared with the participant's condition at screening/baseline. Response choices were: 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: consists 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 4mg | Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 | 2.94 Units on a scale | Standard Deviation 1.29 |
| Brexpiprazole 2 mg | Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 | 2.94 Units on a scale | Standard Deviation 1.34 |
| Brexpiprazole 0.25 mg | Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 | 3.37 Units on a scale | Standard Deviation 1.46 |
| Placebo | Clinical Global Impression- Improvement Scale (CGI-I) Score at Week 6 | 3.48 Units on a scale | Standard Deviation 1.47 |
p-value: 0.000495% CI: [-0.77, -0.22]Cochran-Mantel-Haenszel
p-value: 0.000295% CI: [-0.82, -0.26]Cochran-Mantel-Haenszel
p-value: 0.450595% CI: [-0.5, 0.22]Cochran-Mantel-Haenszel
Secondary
Discontinuation Rate for Lack of Efficacy at Week 6
Time frame: Week 6
Population: Efficacy: consists 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 4mg | Discontinuation Rate for Lack of Efficacy at Week 6 | 3.93 Percentage of participants |
| Brexpiprazole 2 mg | Discontinuation Rate for Lack of Efficacy at Week 6 | 9.44 Percentage of participants |
| Brexpiprazole 0.25 mg | Discontinuation Rate for Lack of Efficacy at Week 6 | 8.05 Percentage of participants |
| Placebo | Discontinuation Rate for Lack of Efficacy at Week 6 | 10.11 Percentage of participants |
p-value: 0.014395% CI: [0.18, 0.85]Cochran-Mantel-Haenszel
p-value: 0.660695% CI: [0.46, 1.65]Cochran-Mantel-Haenszel
p-value: 0.511595% CI: [0.35, 1.68]Cochran-Mantel-Haenszel
Secondary
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
The severity of illness was rated using the CGI-S. To perform this assessment, the rater or 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 participant.
Time frame: Baseline to Week 1, 2, 3, 4 and 5
Population: Efficacy: consists 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 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 3 | -0.72 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 5 | -1.08 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 1 | -0.16 Units on a scale | Standard Error 0.04 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 4 | -0.96 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 2 | -0.46 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 3 | -0.60 Units on a scale | Standard Error 0.06 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 2 | -0.43 Units on a scale | Standard Error 0.05 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 5 | -1.03 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 1 | -0.16 Units on a scale | Standard Error 0.04 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 4 | -0.73 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 2 | -0.18 Units on a scale | Standard Error 0.07 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 5 | -0.73 Units on a scale | Standard Error 0.11 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 4 | -0.58 Units on a scale | Standard Error 0.11 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 3 | -0.33 Units on a scale | Standard Error 0.09 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 1 | -0.11 Units on a scale | Standard Error 0.05 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 5 | -0.69 Units on a scale | Standard Error 0.08 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 1 | -0.14 Units on a scale | Standard Error 0.04 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 2 | -0.30 Units on a scale | Standard Error 0.05 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 3 | -0.51 Units on a scale | Standard Error 0.07 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | Week 4 | -0.54 Units on a scale | Standard Error 0.08 |
p-value: 0.655395% CI: [-0.13, 0.08]Mixed Models Analysis
p-value: 0.61795% CI: [-0.13, 0.08]Mixed Models Analysis
p-value: 0.644695% CI: [-0.1, 0.15]Mixed Models Analysis
p-value: 0.034795% CI: [-0.29, -0.01]Mixed Models Analysis
p-value: 0.082595% CI: [-0.27, 0.02]Mixed Models Analysis
p-value: 0.167895% CI: [-0.05, 0.3]Mixed Models Analysis
p-value: 0.021995% CI: [-0.39, -0.03]Mixed Models Analysis
p-value: 0.327595% CI: [-0.27, 0.09]Mixed Models Analysis
p-value: 0.117395% CI: [-0.04, 0.4]Mixed Models Analysis
p-value: <0.000195% CI: [-0.63, -0.21]Mixed Models Analysis
p-value: 0.066295% CI: [-0.4, 0.01]Mixed Models Analysis
p-value: 0.758795% CI: [-0.3, 0.22]Mixed Models Analysis
p-value: 0.000695% CI: [-0.61, -0.17]Mixed Models Analysis
p-value: 0.003295% CI: [-0.56, -0.11]Mixed Models Analysis
p-value: 0.761995% CI: [-0.32, 0.23]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score.
The PANSS consists of 3 subscales (positive subscale, negative subscale and general psychology subscale) containing a total of 30 symptom constructs and was administered using the Structured Clinical Interview (SCI)-PANSS. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).
Time frame: Baseline to Week 1, 2, 3, 4, 5
Population: Efficacy: consists 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 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -16.50 Units on a scale | Standard Error 1.32 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -9.51 Units on a scale | Standard Error 0.93 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -18.61 Units on a scale | Standard Error 1.42 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -12.78 Units on a scale | Standard Error 1.15 |
| Brexpiprazole 4mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -4.38 Units on a scale | Standard Error 0.6 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -11.08 Units on a scale | Standard Error 1.16 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -14.06 Units on a scale | Standard Error 1.32 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -17.90 Units on a scale | Standard Error 1.43 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -8.86 Units on a scale | Standard Error 0.93 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -4.87 Units on a scale | Standard Error 0.59 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -5.71 Units on a scale | Standard Error 1.65 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -2.52 Units on a scale | Standard Error 0.83 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -3.28 Units on a scale | Standard Error 1.32 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -8.86 Units on a scale | Standard Error 1.9 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -11.87 Units on a scale | Standard Error 2.05 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 4 | -8.89 Units on a scale | Standard Error 1.35 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 2 | -5.11 Units on a scale | Standard Error 0.95 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 1 | -2.87 Units on a scale | Standard Error 0.6 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 3 | -7.64 Units on a scale | Standard Error 1.18 |
| Placebo | Mean Change From Baseline to Week 1, 2, 3, 4 and 5 Positive and Negative Syndrome Scale (PANSS) Total Score. | Week 5 | -10.75 Units on a scale | Standard Error 1.47 |
p-value: 0.064495% CI: [-3.09, 0.09]Mixed Models Analysis
p-value: 0.013995% CI: [-3.58, -0.41]Mixed Models Analysis
p-value: 0.723195% CI: [-1.61, 2.32]Mixed Models Analysis
p-value: 0.001895% CI: [-8.36, -1.93]Mixed Models Analysis
p-value: 0.004595% CI: [-6.33, -1.17]Mixed Models Analysis
p-value: 0.256895% CI: [-1.34, 5.02]Mixed Models Analysis
p-value: 0.000995% CI: [-6.97, -1.82]Mixed Models Analysis
p-value: 0.03695% CI: [-6.67, -0.23]Mixed Models Analysis
p-value: 0.987695% CI: [-4.53, 4.6]Mixed Models Analysis
p-value: <0.000195% CI: [-11.3, -3.93]Mixed Models Analysis
p-value: 0.006295% CI: [-8.85, -1.47]Mixed Models Analysis
p-value: 0.340795% CI: [-2.05, 5.9]Mixed Models Analysis
p-value: 0.000195% CI: [-11.9, -3.86]Mixed Models Analysis
p-value: 0.000595% CI: [-11.2, -3.14]Mixed Models Analysis
p-value: 0.65795% CI: [-6.07, 3.83]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score.
The severity of illness was rated using the CGI-S which is the key secondary endpoint. To perform this assessment, the rater or 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 participant.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 124, 56 and 109 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | -1.20 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | -1.15 Units on a scale | Standard Error 0.08 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | -0.85 Units on a scale | Standard Error 0.12 |
| Placebo | Mean Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score. | -0.82 Units on a scale | Standard Error 0.09 |
Comparison: Difference between the average effect of brexpiprazole 2 and 4 mg/day and placebo was tested first at alpha level of 0.05. If statistically significant, then comparisons for each group (brexpiprazole 2 and 4 mg/day) versus placebo were performed at a significance level of 0.05.p-value: 0.000695% CI: [-0.56, -0.15]Mixed Models Analysis
p-value: 0.001295% CI: [-0.61, -0.15]Mixed Models Analysis
p-value: 0.005695% CI: [-0.56, -0.1]Mixed Models Analysis
p-value: 0.849195% CI: [-0.31, 0.26]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score
The PEC consists of 5 PANSS items (excitement \[P4\], hostility \[P7\], tension \[G4\], uncooperativeness \[G8\], and poor impulse control \[G14\]). Each rated on a scale of 1 (absent) to 7 (extreme). The PEC for participants was calculated as the sum of the rating assigned to each of the 5 items, and ranged from 5 to 35 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score | -2.75 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score | -2.87 Units on a scale | Standard Error 0.34 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score | -1.99 Units on a scale | Standard Error 0.49 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Excited Component (PEC) Score | -1.64 Units on a scale | Standard Error 0.36 |
p-value: 0.024695% CI: [-2.06, -0.14]Mixed Models Analysis
p-value: 0.013195% CI: [-2.19, -0.26]Mixed Models Analysis
p-value: 0.570695% CI: [-1.53, 0.85]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score
For each symptom construct of the PANSS Negative Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS Negative Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score | -3.65 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score | -4.02 Units on a scale | Standard Error 0.36 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score | -3.31 Units on a scale | Standard Error 0.53 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Negative Subscale Score | -2.24 Units on a scale | Standard Error 0.38 |
p-value: 0.006995% CI: [-2.44, 0.39]Mixed Models Analysis
p-value: 0.000795% CI: [-2.81, -0.76]Mixed Models Analysis
p-value: 0.099695% CI: [-2.33, 0.2]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score
For each symptom construct of the PANSS Positive Subscale, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. The symptom constructs were as follows: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS Positive Subscale Score for each participant was calculated as the sum of the rating assigned to each of the 7 subscale items, and ranged from 7 to 49 with a higher score indicating greater severity of symptoms.
Time frame: Baseline to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 123, 56 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score | -6.78 Units on a scale | Standard Error 0.51 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score | -6.57 Units on a scale | Standard Error 0.52 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score | -5.46 Units on a scale | Standard Error 0.74 |
| Placebo | Mean Change From Baseline to Week 6 in PANSS Positive Subscale Score | -4.35 Units on a scale | Standard Error 0.54 |
p-value: 0.00195% CI: [-3.88, -0.99]Mixed Models Analysis
p-value: 0.002995% CI: [-3.67, -0.77]Mixed Models Analysis
p-value: 0.222795% CI: [-2.9, 0.68]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)
The PSP is a clinician-rated scale that measures personal and social functioning in 4 domains: socially useful activities (eg, 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 to Week 6
Population: Efficacy: consists of all participants who received at least one dose of study medication and have baseline and at least one post-baseline efficacy evaluation. At Week 6, 121, 122, 55 and 108 participants in the Brex 4mg, Brex 2mg, Brex 0.25 mg and placebo group, respectively had data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brexpiprazole 4mg | Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) | 12.72 Units on a scale | Standard Error 0.93 |
| Brexpiprazole 2 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) | 13.15 Units on a scale | Standard Error 0.93 |
| Brexpiprazole 0.25 mg | Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) | 11.84 Units on a scale | Standard Error 1.33 |
| Placebo | Mean Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP) | 10.26 Units on a scale | Standard Error 0.98 |
p-value: 0.055795% CI: [-0.06, 4.98]Mixed Models Analysis
p-value: 0.02595% CI: [0.37, 5.42]Mixed Models Analysis
p-value: 0.326495% CI: [-1.58, 4.74]Mixed Models Analysis
Secondary
Response Rate at Week 6
Response rate was defined as improvement in mean change of ≥30% from baseline in PANSS Total Score at Week 6 or CGI-I score of 1 (very much improved) or 2 (much improved) at Week 6.
Time frame: Week 6
Population: Efficacy: consists 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 4mg | Response Rate at Week 6 | 46.07 Percentage of participants |
| Brexpiprazole 2 mg | Response Rate at Week 6 | 47.78 Percentage of participants |
| Brexpiprazole 0.25 mg | Response Rate at Week 6 | 39.08 Percentage of participants |
| Placebo | Response Rate at Week 6 | 30.34 Percentage of participants |
p-value: 0.003295% CI: [1.14, 1.91]Cochran-Mantel-Haenszel
p-value: 0.000495% CI: [1.23, 2.05]Cochran-Mantel-Haenszel
p-value: 0.157695% CI: [0.92, 1.76]Cochran-Mantel-Haenszel