Protocol 331-13-009: An Exploratory, Multicenter, Randomized, Double-Blind, fMRI Study of Fixed-dose Brexpiprazole (OPC-34712) (2 and 4 mg/Day Tablets) in Adults With Schizophrenia With Impulsivity
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task
Study Overview
Brief Summary
The purpose of this study is to evaluate the effect of brexpiprazole, via functional magnetic resonance imaging (fMRI), on the right ventrolateral prefrontal cortex (VLPFC) activated by impulsive behavior.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Are 18 to 65 years of age, inclusive, at the time of informed consent (outpatients only), with a diagnosis of schizophrenia as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria and confirmed by both the M.I.N.I. for Schizophrenia and Psychotic Disorders Studies, and an adequate clinical psychiatric evaluation.
- •Have a CGI-S score of ≤ 4 (moderately ill) at screening and baseline.
- •Have a score of ≤ 4 (moderate) on PANSS item G8 (uncooperativeness) at screening and baseline.
- •Have a BIS-11 score of ≥ 50 at screening and baseline.
- •Willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.
- •Are stable on their current oral antipsychotic medication (no changes within the last month) and are able to meet protocol-required washouts of their current antipsychotic medication.
- •Have received previous outpatient antipsychotic treatment at an adequate dose (at least minimal recommended dose for the treatment of schizophrenia according to the manufacturer labeling) for an adequate duration (at least 6 weeks) and showed a previous good response to such antipsychotic treatment (other than clozapine) in the last 12 months, according to the investigator's opinion.
- •Subjects with eyesight that is sufficient to be able to see visual displays, or correctable with magnet-compatible glasses or contact lenses.
- •Subjects fluent in English
Exclusion Criteria
- •Are presenting with schizophreniform or with a first episode of schizophrenia based on the clinical judgment of the investigator.
- •Have been hospitalized for psychotic symptoms within the previous 6 months.
- •Have a current DSM-IV-TR Axis I primary diagnosis other than schizophrenia, including, but not limited to, schizoaffective disorder, major depressive disorder, bipolar disorder, post-traumatic stress disorder, obsessive-compulsive disorder (OCD) or panic disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, antisocial personality disorders, or mental retardation.
- •Have worsening of ≥ 20% in total PANSS score between the screening and baseline assessments.
- •Experiencing a deterioration in clinical status or an acute exacerbation of schizophrenia in the opinion of the Investigator.
- •Experiencing acute onset of clinically significant depressive symptoms within the past 30 days, according to the investigator's opinion.
- •Answer "Yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS) Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this C-SSRS Item 5 occurred within the last 6 months OR Answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR who, in the opinion of the investigator, present a serious risk of suicide.
- •Have a history of stroke.
- •Contraindications to magnetic resonance imaging (MRI) such as metal prostheses, pacemakers, claustrophobia, movement disorders, waist circumference more than 56 inches or head circumference more than 29 inches, color blindness, significant tremors, or history of head injury or prolonged unconsciousness
Arms & Interventions
Brexpiprazole 2 mg
Brexpiprazole 2 mg/day, once daily dose, tablet, orally
Intervention: Brexpiprazole (Drug)
Brexpiprazole 4 mg
Brexpiprazole 4 mg/day, once daily dose, tablet, orally
Intervention: Brexpiprazole (Drug)
Outcomes
Primary Outcomes
Change From Baseline Brain Activation in the Ventrolateral Prefrontal Cortex (VLPFC) Based on Change From Baseline to Week 6 in fMRI Blood Oxygen-level Dependent (BOLD) Activation Score in the Right VLPFC During Performance of the Go/No-go Task
Time Frame: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants perform tasks designed to assess impulsivity. The tasks to be performed in the scanner included the Go/No-go. Participants were asked to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) \& to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The Go trials were presented at a higher frequency (eg, 75% of the time) than the No-go trials to build up a pre-potent response/response bias. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
Change From Baseline Brain Activation in the VLPFC Based on Change From Baseline to Week 6 in fMRI BOLD Activation Score in the Right VLPFC During Performance of the SSRT Task
Time Frame: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
To evaluate the effect of brexpiprazole on brain regions activated by impulsive behavior (specifically, activation of the right VLPFC). Assessed by fMRI measurements taken when participants performed impulsivity assessment tasks. A white circle was shown for 500ms, followed by a left (\<)/right (\>) arrow. When an arrow was presented, participants responded as fast as possible with their index/middle finger. A titration procedure with 4 staircases started with stop signal delay (SSD) values of 100, 150, 200 \& 250ms to determine participant's SSRT. The tasks included 3 runs with 166 repetition times (TRs), TR=2s; 5 minutes, 32 seconds/run; 96 go trials, 32 stop trials/ run. The total task duration was 16 minutes \& 36 seconds. Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
Secondary Outcomes
- Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)(At baseline (Day 0), and Week 6 (Day 42) of the treatment.)
- Change From Baseline to Week 3 in Go/No-go Task Behavior(At baseline (Day 0), and week 3 (Day 21) of the treatment phase)
- Change From Baseline to Week 3 in PANSS Positive Subscale Score(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in PANSS Negative Subscale Score(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 3 in PANSS Negative Subscale Score(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 3 in fMRI BOLD Activation Score in the Right VLPFC, Scanned by fMRI During Performance of Tasks Associated With Impulsivity (SSRT Task, Go/No-go Task)(At baseline (Day 0), and week 3 (Day 21) of the treatment phase)
- Change From Baseline to Week 3 in BIS-11(At baseline (Day 0), and Week 3 (Day 21) of the treatment.)
- Change From Baseline to Week 6 in Go/No-go Task Behavior(At baseline (Day 0), week 6 (Day 42) of the treatment phase)
- Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 3 in MCQ Score(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in Stop Signal Reaction Time Task (SSRT) Task Behavior(At baseline (Day 0), and Week 6 (Day 42).)
- Change From Baseline to Week 3 in SSRT Task Behavior(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 3 in CPT Behavior(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in Positive and Negative Syndrome Scale (PANSS) Total Score(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 3 in PANSS Total Score(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in PANSS Positive Subscale Score(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score(During trial visits from Day 0 to Week 6 (Day 42).)
- Change From Baseline to Week 3 in CGI-S Score(During trial visits from Day 0 to Week 3 (Day 21).)
- Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6(During trial visits from Day 0 to Week 6 (Day 42).)
- CGI-I Score at Week 3(During trial visits from Day 0 to Week 3 (Day 21).)
- Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)(During trial visits from Day 0 to Week 6 (Day 42).)