Schizophrenia
Conditions
Brief summary
The purpose of this study is to assess the long-term safety, tolerability and efficacy of oral OPC-34712 as monotherapy in adults with 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
Phase A: 1-2 mgs/day by mouth, max of 4 wks. Phase B: 1-4 mgs/day by mouth, up to 52 weeks
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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. Outpatient status at last visit of Trial 331-10-230 or Trial 331-10-231 3. Willing to discontinue all prohibitive psychotropic medications to meet protocol required washouts prior to and during the trial period. 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 |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | From Baseline up to 52 Weeks | A treatment-emergent adverse event (TEAE) is defined as an AE that started after start of investigational medicinal product (IMP) treatment; or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of IMP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in PANSS Positive Subscale Score | From Baseline up to 52 Weeks | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. |
| Mean Change From Baseline in PANSS Negative Subscale Score | From Baseline up to 52 Weeks | The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. |
| Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | From Baseline up to 52 Weeks | The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator were to answer the following question: Considering your total clinical experience with this particular population, how mentally ill was the participant at that time? Response choices include: 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 in Personal and Social Performance Scale Total Score | From Baseline up to 52 Weeks | The PSP was a validated clinician-rated scale that measured personal and social functioning in four 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 that determined 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 Clinical Global Impression - Improvement Score | From Baseline up to 52 Weeks | The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was due to the drug treatment. All responses were compared to the participant's condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). 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. |
| Response Rate | From Baseline up to 52 Weeks | Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit. |
| Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | From Baseline up to 52 Weeks | The PANSS consisted of 3 subscales with 30 symptom constructs (positive subscale (7): delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/perseckion, and hostility; negative subscale (7): blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and conversation flow, stereotyped thinking and general psychopathology subscale (16): somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance). Severity was rated on 7-point scale with scores 1 (absence) & 7 (extremely severe). The PANSS total score was sum of rating scores for 7 positive, 7 negative, and 16 general psychopathology subscale items of PANSS panel. |
| Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | From Baseline up to 52 Weeks | 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). |
| Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | From Baseline up to 52 Weeks | 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 was the sum of the 8 components (delusions (P1), hallucinatory behavior (P3), grandiosity (P5), suspiciousness/persecution (P6), stereotyped thinking (N7), somatic concern (G1), unusual thought content (G9) and lack of judgment and insight (G12)) of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome). |
| Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | From Baseline up to 52 Weeks | 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 (blunted affect (N1), emotional withdrawal (N2), poor rapport (N3), passive/apathetic social withdrawal (N4), lack of spontaneity and conversation flow (N6), motor retardation (G7) and active social avoidance (G16)) of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome). |
| Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | From Baseline up to 52 Weeks | 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 (conceptual disorganization (P2), difficulty in abstract thinking (N5), mannerisms and posturing (G5), disorientation (G10), poor attention (G11), disturbance of volition (G13) and preoccupation (G15)) on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome). |
| Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | From Baseline up to 52 Weeks | 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 (excitement (P4), hostility (P7), uncooperativeness (G8) and poor impulse control (G14)) on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome). |
| Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | From Baseline up to 52 Weeks | 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 (anxiety (G2), guilt feelings (G3), tension (G4) and depression (G6)) on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome). |
| Discontinuation Rate for Lack of Efficacy | From Baseline up to 52 Weeks | Discontinuation rate for the participants who discontinued due to lack of efficacy were examined. |
Countries
Canada, Colombia, Croatia, Japan, Latvia, Malaysia, Mexico, Philippines, Poland, Puerto Rico, Romania, Russia, Serbia, Slovakia, South Korea, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
This trial was conducted in a total of 1072 participants (1044 of whom entered the open-label treatment phase) at 202 trial sites in the following 18 countries: Japan, Korea, Malaysia, Philippines, Taiwan, Croatia, Latvia, Poland, Romania, Russia, Serbia, Turkey, Ukraine, Columbia, Mexico, Canada, Puerto Rico, and United States of America (USA).
Pre-assignment details
Enrollment was drawn from eligible participants who could potentially benefit from monotherapy treatment with oral brexpiprazole for schizophrenia and included rollover participants from the double-blind, phase-3 efficacy trials (ie, Trial NCT01393613, Trial NCT01396421, and Trial NCT01668797) and de novo participants from select sites.
Participants by arm
| Arm | Count |
|---|---|
| Prior Brexpiprazole Participants who rolled over from, and received blinded brexpiprazole in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Vector, NCT01396421; Beacon, NCT01393613; and Equator, NCT01668797); all received 1-4 mg of daily treatment with open label brexpiprazole in trial NCT01397786. | 611 |
| Prior Placebo Participants who rolled over from, and received blinded placebo in, one of the randomized, double-blind, placebo-controlled Phase 3 efficacy studies (Vector, NCT01396421; Beacon, NCT01393613; and Equator, NCT01668797); all received 1-4 mg of daily treatment with open label brexpiprazole in trial NCT01397786. | 204 |
| De Novo Participants who had not previously participated in a brexpiprazole clinical study and who received 1-4 mg of daily treatment with open label brexpiprazole in trial NCT01397786. | 257 |
| Total | 1,072 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase A | Adverse Event | 0 | 0 | 8 |
| Phase A | Lack of Efficacy | 0 | 0 | 1 |
| Phase A | Lost to Follow-up | 0 | 0 | 6 |
| Phase A | Physician Decision | 0 | 0 | 1 |
| Phase A | Subject Met Withdrawal Criteria | 0 | 0 | 7 |
| Phase A | Withdrawal by Subject | 0 | 0 | 5 |
| Phase B | Adverse Event | 109 | 23 | 27 |
| Phase B | Lack of Efficacy | 22 | 7 | 14 |
| Phase B | Lost to Follow-up | 22 | 12 | 22 |
| Phase B | Physician Decision | 9 | 1 | 3 |
| Phase B | Protocol Deviation | 1 | 2 | 4 |
| Phase B | Subject Met Withdrawal Criteria | 38 | 5 | 38 |
| Phase B | Withdrawal by Subject | 102 | 45 | 30 |
Baseline characteristics
| Characteristic | Prior Brexpiprazole | Prior Placebo | De Novo | Total |
|---|---|---|---|---|
| Age, Continuous | 38.5 participants STANDARD_DEVIATION 10.8 | 39.6 participants STANDARD_DEVIATION 10.8 | 44.1 participants STANDARD_DEVIATION 11.1 | 40.0 participants STANDARD_DEVIATION 11.1 |
| Sex: Female, Male Female | 245 Participants | 79 Participants | 85 Participants | 409 Participants |
| Sex: Female, Male Male | 366 Participants | 125 Participants | 172 Participants | 663 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 | 0 / 226 | 166 / 605 | 53 / 202 | 95 / 256 |
| serious Total, serious adverse events | 4 / 226 | 90 / 605 | 18 / 202 | 25 / 224 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs)
A treatment-emergent adverse event (TEAE) is defined as an AE that started after start of investigational medicinal product (IMP) treatment; or if the event was continuous from baseline and was serious, IMP-related, or resulted in death, discontinuation, interruption or reduction of IMP.
Time frame: From Baseline up to 52 Weeks
Population: Safety sample included those participants who had at least one post-baseline efficacy evaluation for Positive and Negative Syndrome Scale (PANSS) total score.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prior Brexpiprazole | Percentage of Participants With Adverse Events (AEs) | With SAEs | 14.9 percentage of participants |
| Prior Brexpiprazole | Percentage of Participants With Adverse Events (AEs) | With TEAEs | 60.0 percentage of participants |
| Prior Brexpiprazole | Percentage of Participants With Adverse Events (AEs) | With AEs | 60.2 percentage of participants |
| Prior Placebo | Percentage of Participants With Adverse Events (AEs) | With SAEs | 8.9 percentage of participants |
| Prior Placebo | Percentage of Participants With Adverse Events (AEs) | With AEs | 56.4 percentage of participants |
| Prior Placebo | Percentage of Participants With Adverse Events (AEs) | With TEAEs | 56.4 percentage of participants |
| De Novo | Percentage of Participants With Adverse Events (AEs) | With TEAEs | 65.2 percentage of participants |
| De Novo | Percentage of Participants With Adverse Events (AEs) | With AEs | 65.2 percentage of participants |
| De Novo | Percentage of Participants With Adverse Events (AEs) | With SAEs | 11.2 percentage of participants |
| Total | Percentage of Participants With Adverse Events (AEs) | With SAEs | 12.9 percentage of participants |
| Total | Percentage of Participants With Adverse Events (AEs) | With TEAEs | 60.4 percentage of participants |
| Total | Percentage of Participants With Adverse Events (AEs) | With AEs | 60.5 percentage of participants |
Secondary
Discontinuation Rate for Lack of Efficacy
Discontinuation rate for the participants who discontinued due to lack of efficacy were examined.
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prior Brexpiprazole | Discontinuation Rate for Lack of Efficacy | 3.6 percentage of participants |
| Prior Placebo | Discontinuation Rate for Lack of Efficacy | 3.5 percentage of participants |
| De Novo | Discontinuation Rate for Lack of Efficacy | 6.3 percentage of participants |
| Total | Discontinuation Rate for Lack of Efficacy | 4.2 percentage of participants |
Secondary
Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score
The severity of illness for each participant was rated using the CGI-S. To perform this assessment, the investigator were to answer the following question: Considering your total clinical experience with this particular population, how mentally ill was the participant at that time? Response choices include: 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: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At at Week 26 (Participant count=375,134,123,632) | -0.35 Units on a scale | Standard Deviation 0.79 |
| Prior Brexpiprazole | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Last Visit (Participant count=591,198,223,1012) | -0.14 Units on a scale | Standard Deviation 1.04 |
| Prior Brexpiprazole | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Week 52 (Participant count=226,93,91,410) | -0.55 Units on a scale | Standard Deviation 0.86 |
| Prior Placebo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At at Week 26 (Participant count=375,134,123,632) | -0.60 Units on a scale | Standard Deviation 0.98 |
| Prior Placebo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Last Visit (Participant count=591,198,223,1012) | -0.46 Units on a scale | Standard Deviation 1.12 |
| Prior Placebo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Week 52 (Participant count=226,93,91,410) | -0.97 Units on a scale | Standard Deviation 0.98 |
| De Novo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Week 52 (Participant count=226,93,91,410) | -0.48 Units on a scale | Standard Deviation 0.86 |
| De Novo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At at Week 26 (Participant count=375,134,123,632) | -0.24 Units on a scale | Standard Deviation 0.88 |
| De Novo | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Last Visit (Participant count=591,198,223,1012) | -0.17 Units on a scale | Standard Deviation 0.88 |
| Total | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At at Week 26 (Participant count=375,134,123,632) | -0.38 Units on a scale | Standard Deviation 0.86 |
| Total | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Last Visit (Participant count=591,198,223,1012) | -0.21 Units on a scale | Standard Deviation 1.03 |
| Total | Mean Change From Baseline in Clinical Global Impression - Severity of Illness Scale Score | At Week 52 (Participant count=226,93,91,410) | -0.63 Units on a scale | Standard Deviation 0.91 |
Secondary
Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/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 (anxiety (G2), guilt feelings (G3), tension (G4) and depression (G6)) on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 26 (Participant count=375,134,123,632) | -0.70 Units on a scale | Standard Deviation 2.6 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Last Visit (Participant count=591,198,223,1012) | -0.20 Units on a scale | Standard Deviation 3.2 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 52 (Participant count=226,93,91,410) | -0.90 Units on a scale | Standard Deviation 2.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 26 (Participant count=375,134,123,632) | -1.50 Units on a scale | Standard Deviation 3 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Last Visit (Participant count=591,198,223,1012) | -0.90 Units on a scale | Standard Deviation 3.4 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 52 (Participant count=226,93,91,410) | -2.40 Units on a scale | Standard Deviation 2.9 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 52 (Participant count=226,93,91,410) | -0.80 Units on a scale | Standard Deviation 3.5 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 26 (Participant count=375,134,123,632) | -0.70 Units on a scale | Standard Deviation 3.4 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Last Visit (Participant count=591,198,223,1012) | -0.40 Units on a scale | Standard Deviation 3.8 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 26 (Participant count=375,134,123,632) | -0.90 Units on a scale | Standard Deviation 2.9 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Last Visit (Participant count=591,198,223,1012) | -0.40 Units on a scale | Standard Deviation 3.4 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Anxiety/Depression Score | At Week 52 (Participant count=226,93,91,410) | -1.20 Units on a scale | Standard Deviation 2.9 |
Secondary
Mean Change From Baseline 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 (conceptual disorganization (P2), difficulty in abstract thinking (N5), mannerisms and posturing (G5), disorientation (G10), poor attention (G11), disturbance of volition (G13) and preoccupation (G15)) on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 26 (Participant count=375,134,123,632) | -1.70 Units on a scale | Standard Deviation 3.3 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Last Visit (Participant count=591,198,223,1012) | -1.20 Units on a scale | Standard Deviation 4.2 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 52 (Participant count=226,93,91,410) | -2.90 Units on a scale | Standard Deviation 3.7 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 26 (Participant count=375,134,123,632) | -2.60 Units on a scale | Standard Deviation 3.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Last Visit (Participant count=591,198,223,1012) | -2.20 Units on a scale | Standard Deviation 4.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 52 (Participant count=226,93,91,410) | -3.70 Units on a scale | Standard Deviation 4.6 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 52 (Participant count=226,93,91,410) | -2.30 Units on a scale | Standard Deviation 3.7 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 26 (Participant count=375,134,123,632) | -1.70 Units on a scale | Standard Deviation 3.5 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Last Visit (Participant count=591,198,223,1012) | -0.90 Units on a scale | Standard Deviation 4 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 26 (Participant count=375,134,123,632) | -1.90 Units on a scale | Standard Deviation 3.4 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Last Visit (Participant count=591,198,223,1012) | -1.40 Units on a scale | Standard Deviation 4.2 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Disorganized Thought Score | At Week 52 (Participant count=226,93,91,410) | -2.90 Units on a scale | Standard Deviation 4 |
Secondary
Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ 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 (excitement (P4), hostility (P7), uncooperativeness (G8) and poor impulse control (G14)) on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 26 (Participant count=375,134,123,632) | -0.40 Units on a scale | Standard Deviation 2.7 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Last Visit (Participant count=591,198,223,1012) | 0.20 Units on a scale | Standard Deviation 3.4 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 52 (Participant count=226,93,91,410) | -0.80 Units on a scale | Standard Deviation 2.7 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 26 (Participant count=375,134,123,632) | -1.40 Units on a scale | Standard Deviation 3.1 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Last Visit (Participant count=591,198,223,1012) | -0.70 Units on a scale | Standard Deviation 3.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 52 (Participant count=226,93,91,410) | -1.90 Units on a scale | Standard Deviation 2.9 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 52 (Participant count=226,93,91,410) | -0.90 Units on a scale | Standard Deviation 2.3 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 26 (Participant count=375,134,123,632) | -0.60 Units on a scale | Standard Deviation 2.6 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Last Visit (Participant count=591,198,223,1012) | -0.30 Units on a scale | Standard Deviation 3 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 26 (Participant count=375,134,123,632) | -0.60 Units on a scale | Standard Deviation 2.8 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Last Visit (Participant count=591,198,223,1012) | -0.10 Units on a scale | Standard Deviation 3.4 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Hostility/ Excitement Score | At Week 52 (Participant count=226,93,91,410) | -1.10 Units on a scale | Standard Deviation 2.7 |
Secondary
Mean Change From Baseline 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 (blunted affect (N1), emotional withdrawal (N2), poor rapport (N3), passive/apathetic social withdrawal (N4), lack of spontaneity and conversation flow (N6), motor retardation (G7) and active social avoidance (G16)) of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -1.50 Units on a scale | Standard Deviation 3.6 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -1.00 Units on a scale | Standard Deviation 4.1 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -2.60 Units on a scale | Standard Deviation 4.3 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -2.20 Units on a scale | Standard Deviation 4 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -2.30 Units on a scale | Standard Deviation 5.1 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -3.90 Units on a scale | Standard Deviation 5 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -2.20 Units on a scale | Standard Deviation 3.8 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -1.70 Units on a scale | Standard Deviation 4.1 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -0.70 Units on a scale | Standard Deviation 4.1 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -1.70 Units on a scale | Standard Deviation 3.8 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -1.20 Units on a scale | Standard Deviation 4.4 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Negative Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -2.80 Units on a scale | Standard Deviation 4.4 |
Secondary
Mean Change From Baseline 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 was the sum of the 8 components (delusions (P1), hallucinatory behavior (P3), grandiosity (P5), suspiciousness/persecution (P6), stereotyped thinking (N7), somatic concern (G1), unusual thought content (G9) and lack of judgment and insight (G12)) of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -2.60 Units on a scale | Standard Deviation 4.8 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -1.60 Units on a scale | Standard Deviation 5.9 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -3.90 Units on a scale | Standard Deviation 5.2 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -4.70 Units on a scale | Standard Deviation 5.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -3.50 Units on a scale | Standard Deviation 6.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -6.60 Units on a scale | Standard Deviation 5.7 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -2.60 Units on a scale | Standard Deviation 4.8 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -2.00 Units on a scale | Standard Deviation 5.2 |
| De Novo | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -1.30 Units on a scale | Standard Deviation 5 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 26 (Participant count=375,134,123,632) | -2.90 Units on a scale | Standard Deviation 5.1 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Last Visit (Participant count=591,198,223,1012) | -1.90 Units on a scale | Standard Deviation 5.9 |
| Total | Mean Change From Baseline in PANSS Marder Factor Scores - Positive Symptoms Score | At Week 52 (Participant count=226,93,91,410) | -4.20 Units on a scale | Standard Deviation 5.4 |
Secondary
Mean Change From Baseline in PANSS Negative Subscale Score
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In negative subscale the severity was rated for the following 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking.
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 26 (Participant count=375,134,123,632) | -1.40 Units on a scale | Standard Deviation 3.7 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Negative Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -1.00 Units on a scale | Standard Deviation 4.1 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 52 (Participant count=226,93,91,410) | -2.70 Units on a scale | Standard Deviation 4.5 |
| Prior Placebo | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 26 (Participant count=375,134,123,632) | -2.40 Units on a scale | Standard Deviation 4.3 |
| Prior Placebo | Mean Change From Baseline in PANSS Negative Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -2.40 Units on a scale | Standard Deviation 5 |
| Prior Placebo | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 52 (Participant count=226,93,91,410) | -3.70 Units on a scale | Standard Deviation 5.4 |
| De Novo | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 52 (Participant count=226,93,91,410) | -2.00 Units on a scale | Standard Deviation 3.7 |
| De Novo | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 26 (Participant count=375,134,123,632) | -1.30 Units on a scale | Standard Deviation 3.8 |
| De Novo | Mean Change From Baseline in PANSS Negative Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -0.60 Units on a scale | Standard Deviation 4.2 |
| Total | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 26 (Participant count=375,134,123,632) | -1.60 Units on a scale | Standard Deviation 3.9 |
| Total | Mean Change From Baseline in PANSS Negative Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -1.20 Units on a scale | Standard Deviation 4.3 |
| Total | Mean Change From Baseline in PANSS Negative Subscale Score | At Week 52 (Participant count=226,93,91,410) | -2.80 Units on a scale | Standard Deviation 4.6 |
Secondary
Mean Change From Baseline in PANSS Positive Subscale Score
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility.
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 26 (Participant count=375,134,123,632) | -2.10 Units on a scale | Standard Deviation 4.5 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Positive Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -0.90 Units on a scale | Standard Deviation 5.9 |
| Prior Brexpiprazole | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 52 (Participant count=226,93,91,410) | -3.20 Units on a scale | Standard Deviation 4.6 |
| Prior Placebo | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 26 (Participant count=375,134,123,632) | -4.10 Units on a scale | Standard Deviation 5.4 |
| Prior Placebo | Mean Change From Baseline in PANSS Positive Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -2.80 Units on a scale | Standard Deviation 6.4 |
| Prior Placebo | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 52 (Participant count=226,93,91,410) | -5.80 Units on a scale | Standard Deviation 5.2 |
| De Novo | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 52 (Participant count=226,93,91,410) | -2.30 Units on a scale | Standard Deviation 4.1 |
| De Novo | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 26 (Participant count=375,134,123,632) | -1.70 Units on a scale | Standard Deviation 4.3 |
| De Novo | Mean Change From Baseline in PANSS Positive Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -1.00 Units on a scale | Standard Deviation 4.9 |
| Total | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 26 (Participant count=375,134,123,632) | -2.40 Units on a scale | Standard Deviation 4.7 |
| Total | Mean Change From Baseline in PANSS Positive Subscale Score | At Last Visit (Participant count=591,198,223,1012) | -1.30 Units on a scale | Standard Deviation 5.8 |
| Total | Mean Change From Baseline in PANSS Positive Subscale Score | At Week 52 (Participant count=226,93,91,410) | -3.60 Units on a scale | Standard Deviation 4.8 |
Secondary
Mean Change From Baseline in Personal and Social Performance Scale Total Score
The PSP was a validated clinician-rated scale that measured personal and social functioning in four 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 that determined 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: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 26 (Participant count=366,134,123,623) | 4.50 Units on a scale | Standard Deviation 9.7 |
| Prior Brexpiprazole | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Last Visit (Participant count=569,196,219,984) | 1.80 Units on a scale | Standard Deviation 12.4 |
| Prior Brexpiprazole | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 52 (Participant count=223,93,91,407) | 7.00 Units on a scale | Standard Deviation 10.6 |
| Prior Placebo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 26 (Participant count=366,134,123,623) | 6.50 Units on a scale | Standard Deviation 11.3 |
| Prior Placebo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Last Visit (Participant count=569,196,219,984) | 5.10 Units on a scale | Standard Deviation 12.8 |
| Prior Placebo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 52 (Participant count=223,93,91,407) | 9.60 Units on a scale | Standard Deviation 11.9 |
| De Novo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 52 (Participant count=223,93,91,407) | 7.60 Units on a scale | Standard Deviation 10.8 |
| De Novo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 26 (Participant count=366,134,123,623) | 4.50 Units on a scale | Standard Deviation 9 |
| De Novo | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Last Visit (Participant count=569,196,219,984) | 2.70 Units on a scale | Standard Deviation 11 |
| Total | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 26 (Participant count=366,134,123,623) | 4.90 Units on a scale | Standard Deviation 10 |
| Total | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Last Visit (Participant count=569,196,219,984) | 2.70 Units on a scale | Standard Deviation 12.2 |
| Total | Mean Change From Baseline in Personal and Social Performance Scale Total Score | At Week 52 (Participant count=223,93,91,407) | 7.70 Units on a scale | Standard Deviation 11 |
Secondary
Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component 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: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Last Visit (Participant count=591,198,223,1012) | 0.10 Units on a scale | Standard Deviation 4.1 |
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 52 (Participant count=226,93,91,410) | -1.20 Units on a scale | Standard Deviation 3.2 |
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 26 (Participant count=375,134,123,632) | -0.60 Units on a scale | Standard Deviation 3.1 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 52 (Participant count=226,93,91,410) | -2.60 Units on a scale | Standard Deviation 3.4 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 26 (Participant count=375,134,123,632) | -1.80 Units on a scale | Standard Deviation 3.7 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Last Visit (Participant count=591,198,223,1012) | -0.90 Units on a scale | Standard Deviation 4.2 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 26 (Participant count=375,134,123,632) | -0.70 Units on a scale | Standard Deviation 3.1 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Last Visit (Participant count=591,198,223,1012) | -0.30 Units on a scale | Standard Deviation 3.5 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 52 (Participant count=226,93,91,410) | -1.00 Units on a scale | Standard Deviation 2.9 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 52 (Participant count=226,93,91,410) | -1.50 Units on a scale | Standard Deviation 3.2 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Week 26 (Participant count=375,134,123,632) | -0.90 Units on a scale | Standard Deviation 3.3 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Excited Component Score | At Last Visit (Participant count=591,198,223,1012) | -0.20 Units on a scale | Standard Deviation 4 |
Secondary
Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score
The PANSS consisted of 3 subscales with 30 symptom constructs (positive subscale (7): delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/perseckion, and hostility; negative subscale (7): blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and conversation flow, stereotyped thinking and general psychopathology subscale (16): somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation, and active social avoidance). Severity was rated on 7-point scale with scores 1 (absence) & 7 (extremely severe). The PANSS total score was sum of rating scores for 7 positive, 7 negative, and 16 general psychopathology subscale items of PANSS panel.
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 26 (Participant count=375,134,123,632) | -6.90 Units on a scale | Standard Deviation 12.9 |
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Last Visit (Participant count=591,198,223,1012) | -3.80 Units on a scale | Standard Deviation 16.7 |
| Prior Brexpiprazole | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 52 (Participant count= 226,93,91,410) | -11.0 Units on a scale | Standard Deviation 14.4 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 26 (Participant count=375,134,123,632) | -12.50 Units on a scale | Standard Deviation 14.9 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Last Visit (Participant count=591,198,223,1012) | -9.70 Units on a scale | Standard Deviation 18.7 |
| Prior Placebo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 52 (Participant count= 226,93,91,410) | -18.40 Units on a scale | Standard Deviation 16.9 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 52 (Participant count= 226,93,91,410) | -8.80 Units on a scale | Standard Deviation 12.6 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 26 (Participant count=375,134,123,632) | -6.60 Units on a scale | Standard Deviation 13.6 |
| De Novo | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Last Visit (Participant count=591,198,223,1012) | -3.50 Units on a scale | Standard Deviation 14.3 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 26 (Participant count=375,134,123,632) | -8.00 Units on a scale | Standard Deviation 13.6 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Last Visit (Participant count=591,198,223,1012) | -4.90 Units on a scale | Standard Deviation 16.8 |
| Total | Mean Change From Baseline in Positive and Negative Syndrome Scale Total Score | At Week 52 (Participant count= 226,93,91,410) | -12.20 Units on a scale | Standard Deviation 15 |
Secondary
Mean Clinical Global Impression - Improvement Score
The efficacy of study medication was rated for each participant using the CGI-I. The investigator rated the participant's total improvement whether or not it was due to the drug treatment. All responses were compared to the participant's condition at Screening/Baseline (i.e, Week 6 visit of Protocol NCT00905307). 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: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prior Brexpiprazole | Mean Clinical Global Impression - Improvement Score | At Week 26 (Participant count=381,134,123,638) | 3.00 Units on a scale | Standard Deviation 1.13 |
| Prior Brexpiprazole | Mean Clinical Global Impression - Improvement Score | At Last Visit (Participant count=598,198,223,1019) | 3.31 Units on a scale | Standard Deviation 1.43 |
| Prior Brexpiprazole | Mean Clinical Global Impression - Improvement Score | At Week 52 (Participant count=226,93,91,410) | 2.66 Units on a scale | Standard Deviation 1.13 |
| Prior Placebo | Mean Clinical Global Impression - Improvement Score | At Week 26 (Participant count=381,134,123,638) | 2.77 Units on a scale | Standard Deviation 0.99 |
| Prior Placebo | Mean Clinical Global Impression - Improvement Score | At Last Visit (Participant count=598,198,223,1019) | 2.96 Units on a scale | Standard Deviation 1.33 |
| Prior Placebo | Mean Clinical Global Impression - Improvement Score | At Week 52 (Participant count=226,93,91,410) | 2.26 Units on a scale | Standard Deviation 0.97 |
| De Novo | Mean Clinical Global Impression - Improvement Score | At Week 52 (Participant count=226,93,91,410) | 2.76 Units on a scale | Standard Deviation 1.09 |
| De Novo | Mean Clinical Global Impression - Improvement Score | At Week 26 (Participant count=381,134,123,638) | 3.00 Units on a scale | Standard Deviation 1.13 |
| De Novo | Mean Clinical Global Impression - Improvement Score | At Last Visit (Participant count=598,198,223,1019) | 3.30 Units on a scale | Standard Deviation 1.27 |
| Total | Mean Clinical Global Impression - Improvement Score | At Week 26 (Participant count=381,134,123,638) | 2.95 Units on a scale | Standard Deviation 1.1 |
| Total | Mean Clinical Global Impression - Improvement Score | At Last Visit (Participant count=598,198,223,1019) | 3.24 Units on a scale | Standard Deviation 1.38 |
| Total | Mean Clinical Global Impression - Improvement Score | At Week 52 (Participant count=226,93,91,410) | 2.59 Units on a scale | Standard Deviation 1.1 |
Secondary
Response Rate
Response rate was defined as a reduction of ≥ 30% from Baseline in PANSS total score or CGI-I score of 1 (very much improved) or 2 (much improved) at the Last Visit.
Time frame: From Baseline up to 52 Weeks
Population: The Efficacy Sample included participants in the Safety Sample who had at least 1 post-baseline efficacy evaluation for PANSS Total Score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prior Brexpiprazole | Response Rate | 34.2 percentage of participants |
| Prior Placebo | Response Rate | 42.6 percentage of participants |
| De Novo | Response Rate | 27.2 percentage of participants |
| Total | Response Rate | 34.3 percentage of participants |