Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia (EQUATOR)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults With Schizophrenia

The purpose of this study is to evaluate the efficacy of brexpiprazole compared with placebo as maintenance treatment in adults with schizophrenia.

Study Overview

• Status: Completed
• Conditions: Acute Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Brexpiprazole

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.

• Study Type: Interventional
• Enrollment (Actual): 524
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Barranquilla, Colombia, 00000
  • Bello, Colombia, 00000
  • Bogota, Colombia, 00000
  • Pereira, Colombia, 00000
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
  • Kuala Lumpur, Malaysia, 56000
  • Sabah, Malaysia, 88815
  • Kelantan
    • Kota Bahru, Kelantan, Malaysia, 15586
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
• Puerto Rico
  • San Juan, Puerto Rico, 00918
  • San Juan, Puerto Rico, 00927
• Romania
  • Arad, Romania, 310022
  • Brasov, Romania, 500123
  • Bucuresti, Romania, 041914
  • Craiova, Romania, 200473
  • Focsani, Romania, 620165
  • Iasi, Romania, 700282
  • Pitesti, Romania, 110069
  • Targoviste, Romania, 130086
• Serbia
  • Belgrade, Serbia, 11000
  • Belgrade, Serbia, 11040
  • Kragujevac, Serbia, 34000
  • Novi Knezevac, Serbia, 23330
  • Novi Sad, Serbia, 21000
• Turkey
  • Denizli, Turkey, 20070
  • Diyarbakir, Turkey, 21280
  • Kocaeli, Turkey, 41380
• Ukraine
  • Kharkiv, Ukraine, 61068
  • Kharkiv, Ukraine, 61036
  • Kherson,Vil. Stepanivka, Ukraine, 73488
  • Kyiv, Ukraine, 02660
  • Kyiv, Ukraine, 04080
  • Lviv, Ukraine, 79021
  • Odesa, Ukraine, 65014
  • Simferopol, Ukraine, 95006
• United States
  • California
    • Anaheim, California, United States, 92805
    • Cerritos, California, United States, 90703
    • Garden Grove, California, United States, 92845
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92102
  • Florida
    • Tampa, Florida, United States, 33613
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
  • Missouri
    • St. Charles, Missouri, United States, 63304
    • St. Louis, Missouri, United States, 63141
  • Nebraska
    • North Platte, Nebraska, United States, 69101
  • Nevada
    • Las Vegas, Nevada, United States, 89102
  • Tennessee
    • Memphis, Tennessee, United States, 38119
  • Texas
    • Dallas, Texas, United States, 75231
  • Virginia
    • Richmond, Virginia, United States, 23230

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age 18 years or older to less than 65 years, inclusive (at time of informed consent)
• Subjects with a current diagnosis of schizophrenia, as defined by DSM-IV-TR criteria and a history of the illness for at least three years prior to screening (as per subject, family, healthcare provider, or by previous medical records).
• Subjects with a stable living environment, as demonstrated by the ability to provide contact information for themselves and/or family/friend(s)/caregiver(s).
• Subjects who showed previous response to antipsychotic treatment in the past year.
• Subjects who are currently treated with oral or depot antipsychotics other than clozapine or who have had a recent lapse in antipsychotic treatment requiring chronic treatment with antipsychotic medication for stabilization.
• Subjects who are experiencing a current acute exacerbation of psychotic symptoms requiring stabilization
• Subjects with a history of relapse and/or exacerbation of symptoms when they are not receiving antipsychotic treatment.

Exclusion Criteria:

• Female patients who are breastfeeding or who have a positive pregnancy test (urine) result prior to receiving investigational medicinal product
• Patients presenting a first episode of schizophrenia based on the clinical judgment of the investigator
• Patients who are diagnosed with a disease other than schizophrenia (schizoaffective disorder, major depressive disorder, bipolar disorder, posttraumatic stress disorder, anxiety disorder, delirium, dementia, amnesia, or other cognitive disorder) based on current DSM-IV-TR Axis Ι criteria, or who are diagnosed with a personality disorder (borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial)
• Subjects experiencing acute depressive symptoms within the past 30 days
• Subjects with schizophrenia who are considered resistant/refractory to antipsychotic treatment by history
• Subjects with a significant risk of violent behavior; who represent a risk of committing suicide
• Subjects with clinically significant tardive dyskinesia
• Subjects currently treated with insulin for diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo comparator for 52 weeks	Drug: Placebo; Placebo comparator for 52 weeks
EXPERIMENTAL: Brexpiprazole (OPC-34712); Brexpiprazole (OPC-34712) for 52 weeks	Drug: Brexpiprazole; Brexpiprazole tablets 1 to 4 mg /day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomization to Exacerbation of Psychotic Symptoms/Impending Relapse in Phase C.	The primary efficacy variable was time to impending relapse from randomization, as assessed by Clinical Global Impression of Improvement (CGI-I) score ≥5, Positive and Negative Syndrome Scale (PANSS) scores for hostility or uncooperativeness ≥5, or ≥20% increase in PANSS Total Score. Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score >4 with an absolute increase of ≥ 2 on that specific item or absolute increase of ≥ 4 on the combined 4 PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content).OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Any suicidal behavior or answers of "yes" to Questions 4 or 5 on the suicidal ideation section of the C-SSRS OR 5) Violent or aggressive behavior resulting in clinically significant injury.The measure type, number is Hazard Ratio.	From randomization to time of exacerbation of psychotic symptoms/impending relapse - up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting Exacerbation of Psychotic Symptoms/Impending Relapse Criteria in the Double-blind Maintenance Phase	Impending relapse was defined as meeting any of the following 5 criteria: 1) CGI-I score of ≥ 5 (minimally worse) and increase in individual PANSS items to a score > 4 with an absolute increase of ≥ 2 on that specific item or an increase on any of the following individual PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual though content) to a score of >4 and an absolute increase of ≥ 4 on the combined 4 PANSS items. OR 2) CGI-I score of 6 or 7 (much or very much worse) OR 3) Hospitalization due to worsening of illness OR 4) Current suicidal behavior as assessed by the C-SSRS (ie, an answer of "yes" to any of the questions on the suicidal behavior section of the C-SSRS 5) Violent or aggressive behavior resulting in clinically significant self-injury to another person, or property damage.	Baseline and Week 52/Early Termination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Meeting Stability Criteria in Double Blind Maintenance Phase	Participants were assessed for stability using the following criteria:1) Outpatient status AND 2) Positive and Negative Syndrome Scale (PANSS) Total Score ≤ 70 AND 3) A score of ≤ 4 (moderate) on each of the following PANSS items (possible scores of 1 to 7 for each item): conceptual disorganization, suspiciousness hallucinatory behavior, unusual thought content, AND 4) Clinical Global Impression - Severity of Illness scale(CGI-S) score ≤ 4 (moderately ill) AND 5) No current suicidal behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), defined as the following: An answer of "no" to each question on the Suicidal Behavior section of the C-SSRS AND an answer of "no" to Questions 4 and 5 on the Suicidal Ideation section of the C-SSRS, if completed, AND 6) No evidence of aggressive or violent behavior resulting in clinically significant self-injury, injury to another person, property damage.	Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score - MMRM Analysis	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Total Score - Last-observation-carried-forward (LOCF) Analysis	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS total score was the sum of the rating scores for 7 positive scale items, 7 negative scale items, and 16 general psychopathology scale items from the PANSS panel. The PANSS total score ranged from 30 (best possible outcome) to 210 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Positive Subscale Score - MMRM Analysis	PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Positive Subscale Score - LOCF Analysis	PANSS consisted of three subscales: a total of 30 symptom constructs. For each construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS positive subscale score was the sum of the rating scores for the 7 positive scale items from the PANSS panel. The 7 positive symptom constructs are delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. The PANSS positive subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Negative Subscale Score - MMRM Analysis	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Negative Subscale Score - LOCF Analysis	The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, stereotyped thinking. The PANSS negative subscale score ranged from 7 (best possible outcome) to 49 (worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint - MMRM Analysis	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.	Baseline, Weeks 6, 12, 24, 36 and 52
Change From Baseline in CGI-S Score at Endpoint - LOCF Analysis	The severity of illness for each participant was rated using the CGI-S scale. To assess CGI-S, the study physician answered the following question: "Considering your total clinical experience with this particular population, how mentally ill is the participant at this time?" Response choices included: 0 = not assessed; 1 = normal, not ill at all; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.	Baseline and Weeks 6, 12, 24, 36 and 52
Clinical Global Impression - Improvement Score (CGI-I) at Endpoint - LOCF Analysis	The rater or investigator would rate the participant's total improvement whether or not it is due entirely to study treatment. During Phase B, responses were compared to the participant's condition at Baseline of Phase B (for participants who entered Phase B directly after screening) or to the End of Phase A visit (for participants who participated in Phase A). During Phase C, responses were compared to the participant's condition at the End of Phase B visit. Response choices include: 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.	Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in Personal and Social Performance (PSP) Scale Score - MMRM Analysis	The PSP is a validated clinician-rated scale that measures 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 is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are 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 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision.The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning.	Baseline and Weeks 24 and 52
Mean Change From Baseline in PSP Scale Score - LOCF Analysis	The PSP is a validated clinician-rated scale that measures 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 is rated as absent, mild, manifest, marked, severe, or very severe. These ratings are 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 are considered to have mild functional difficulty. Scores of 31 to 70 represent manifest disabilities of various degrees and ratings of 1 to 30 indicate minimal functioning that requires intense support and/or supervision.The PSP score ranges from 0 to 100, with higher scores indicating higher levels of social functioning.	Baseline and Weeks 24 and 52
Mean Change From Baseline in Global Assessment of Functioning (GAF) Scale Score - MMRM Analysis	The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor.	Baseline and Weeks 12, 24, 36 and 52
Mean Change From Baseline in GAF Scale Score - LOCF Analysis	The GAF is a clinician-rated scale that assesses the participant's psychological, social, and occupational functioning on a hypothetical continuum of mental health-illness using a scale that ranges from 1 to 100 score, where lower values indicate worst outcome. From among 10 descriptive anchors, investigators will choose the anchor which is the most representative of the participant's level of functioning at the time of the assessment and will assign a single score within the point range given for the selected anchor.	Baseline and Weeks 12, 24, 36 and 52
Percentage of Participants Who Discontinued Due to All Causes	Analysis of the percentage of participants who discontinued due to all causes was based on all participants who have been randomized and taken one dose of IMP in the Double-blind Maintenance phase. The trial was completed by sponsor when efficacy was demonstrated at the first pre-specified interim analysis (45 impending relapse events) performed by an independent (unblinded) statistician.	Baseline to Week 52
Mean Change From Baseline in PANSS Excited Component (PEC) Score - MMRM Analysis	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).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PEC Score - LOCF Analysis	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).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - MMRM Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Positive Symptoms Score - LOCF Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The positive factor score is the sum of the 8 components of the positive symptoms scale (range: 8 - best possible outcome to 56 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - MMRM Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Negative Symptoms Score - LOCF Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The negative factor score is the sum of the 7 items of the negative subscale (range: 8 - best possible outcome to 56 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - MMRM Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Disorganized Thought Score - LOCF Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The disorganized thoughts factor score is the sum of score from the 7 items on the disorganized thoughts subscale (range: 7 - best possible outcome to 49 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - MMRM Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Uncontrolled Hostility/Excitement Score - LOCF Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The uncontrolled hostility/excitement factor score is the sum of score from the 4 items on the uncontrolled hostility/excitement subscale (range: 4 - best possible outcome to 28 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - MMRM Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52
Mean Change From Baseline in PANSS Marder Factor Scores: Anxiety/Depression Score - LOCF Analysis	Retrospective factor analyses have been performed in recent decades using scores for the 30 individual PANSS items to categorize symptoms into 5 dimensions. Collectively, these dimensions are referred to as the PANSS Marder Factor scores and include positive symptoms score, negative symptoms score, thought score, uncontrolled hostility/excitement, anxiety depression score. The anxiety/depression factor score is the sum of score from the 4 items on the anxiety/depression subscale (range: 4 - best possible outcome to 28 - worst possible outcome).	Baseline and Weeks 6, 12, 24, 36 and 52

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Quintiles, Inc.

Publications and helpful links

General Publications

• Correll CU, He Y, Therrien F, MacKenzie E, Meehan SR, Weiss C, Hefting N, Hobart M. Effects of Brexpiprazole on Functioning in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies. J Clin Psychiatry. 2022 Mar 1;83(2):20m13793. doi: 10.4088/JCP.20m13793.
• Marder SR, Meehan SR, Weiss C, Chen D, Hobart M, Hefting N. Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies. Schizophr Bull Open. 2021 May 1;2(1):sgab014. doi: 10.1093/schizbullopen/sgab014. eCollection 2021 Jan.
• Correll CU, Shi L, Weiss C, Hobart M, Eramo A, Duffy RA, Weiller E, Baker RA. Successful switching of patients with acute schizophrenia from another antipsychotic to brexpiprazole: comparison of clinicians' choice of cross-titration schedules in a post hoc analysis of a randomized, double-blind, maintenance treatment study. CNS Spectr. 2019 Oct;24(5):507-517. doi: 10.1017/S1092852918001086.
• Fleischhacker WW, Hobart M, Ouyang J, Forbes A, Pfister S, McQuade RD, Carson WH, Sanchez R, Nyilas M, Weiller E. Efficacy and Safety of Brexpiprazole (OPC-34712) as Maintenance Treatment in Adults with Schizophrenia: a Randomized, Double-Blind, Placebo-Controlled Study. Int J Neuropsychopharmacol. 2017 Jan 1;20(1):11-21. doi: 10.1093/ijnp/pyw076.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: August 16, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (ESTIMATE): August 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 13, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Dopamine Agonists; Dopamine Agents; Brexpiprazole
• Other Study ID Numbers: 331-10-232; 2011-005766-38 (EUDRACT_NUMBER)