Schizophrenia With ImpulsivityPhase 3NCT02194933
Monotherapy Brexpiprazole (OPC-34712) Trial in the Treatment of Adults With Schizophrenia With Impulsivity
A Phase 3 study testing Brexpiprazole in people with Schizophrenia With Impulsivity, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia With Impulsivity
- What is being tested?
- Brexpiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to Apr 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California at Irvine Medical Center
Orange, California, 92868
About this study
Official title: 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
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.
- Conditions
- Schizophrenia With Impulsivity
- Being tested
- Brexpiprazole
- Keywords
- Schizophrenia, Mental Disorders, Antipsychotic,, Psychotic disorder, Impulsivity
- Medical subject headings
- Schizophrenia, Mental Disorders, Psychotic Disorders, Impulsive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called OPC-34712
Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Brexpiprazole 2 mg | Experimental | Brexpiprazole 2 mg/day, once daily dose, tablet, orally Receives: Drug: Brexpiprazole |
| Brexpiprazole 4 mg | Experimental | Brexpiprazole 4 mg/day, once daily dose, tablet, orally Receives: Drug: Brexpiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
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
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.
Measured: At baseline (Day 0), and week 6 (Day 42) of the treatment phase
Secondary outcomes (22)
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)
Go/No-go: Participants were to press button fast to Stimulus A (neutral face) (Go trials) \& to NOT press button to Stimulus B (happy face) (No-go trials). Task comprised 4 runs of 3 minutes \& 8 seconds each. Each run included 36 target (Go) \& 13 non target (No-go) stimuli. The stimuli were presented for 500ms with 2 to 14.5 inter-stimulus interval fixation cross in between. Target stimuli were pseudo-randomized across runs so that each participant was presented with 2 Happy Go \& 2 Neutral Go conditions.
SSRT: White circle was shown for 500ms, followed by left (<)/right (>) arrow. When an arrow was presented, participants were to respond fast with their index/middle finger. A titration procedure with 4 staircases that started with stop signal delay (SSD) values of 100, 150, 200 \& 250ms determined participant's SSRT.
Scores were not bounded by a minimum or maximum range, higher fMRI BOLD activation scores indicate increased brain blood flow, which reflects brain activity.
Measured: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)
A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.
Measured: At baseline (Day 0), and Week 6 (Day 42) of the treatment.
Change From Baseline to Week 3 in BIS-11
A participant-rated scale was used to assess impulsive personality traits. The BIS-11 consisted of 30 items scored on a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/ always) and the scores were used to assess 6 first-order factors (attention, motor, self-control, cognitive complexity, perseverance and cognitive instability impulsiveness) and 3 second-order factors ( motor impulsiveness, nonplanning impulsiveness and attentional impulsiveness). The total score ranged from 30 to 120 with higher scores indicating impulsive personality traits, and took 10 to 15 minutes to complete the BIS-11.
Measured: At baseline (Day 0), and Week 3 (Day 21) of the treatment.
Change From Baseline to Week 6 in Go/No-go Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).
Measured: At baseline (Day 0), week 6 (Day 42) of the treatment phase
Change From Baseline to Week 3 in Go/No-go Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in false alarm rate on the Go/No-go task (a lower false alarm rate was suggestive of better inhibition). Participants were instructed to press a button as fast as they could to Stimulus A (eg, neutral face) that appeared on the screen (Go trials) and to NOT press a button to Stimulus B (eg, happy face) that appeared on the screen (No-go trials). The stimuli were presented randomly. The value calculated was the rate of incorrect response for each condition (Go and No-go).
Measured: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score
To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity. It took 5 to10 minutes to complete the MCQ
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in MCQ Score
To measure "delay discounting" as an index of impulsive behavior. It measured the extent to which the value of a reward decreased as the delay to obtaining that reward increased. The propensity of participants to delay reward was assessed with an MCQ. Discounting rate is estimated using, k= (A/V)1/D, where k is the discounting rate parameter, V is the immediate reward, A is the higher delayed reward and D is the amount of days to the delayed reward. The MCQ consisted of 27 choices between immediate and delayed rewards. The participants chose repeatedly between 2 hypothetical sums of money: a smaller amount now or a larger amount in the future (ex: ''Would you prefer $27 today or $50 in 21 days?"). The answers provided an estimate of the participant's discounting rate. The discounting rate parameter takes values between 0 and 1 and higher discounting rates indicated impulsivity.
Measured: 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
Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). 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. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with \& without a response
Measured: At baseline (Day 0), and Week 6 (Day 42).
Change From Baseline to Week 3 in SSRT Task Behavior
Brexpiprazole reduced impulsivity was measured by a change in Stop Signal Reaction Time (SSRT) on the SSRT task (a lower SSRT was suggestive of better inhibition). 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. During scanning, the SSD was dynamically adjusted to yield a 50% successful inhibition rate, so that SSRT could be estimated for each participant. This resulted in approximately equal proportions of stop trials with \& without a response
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior
The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in CPT Behavior
The AX trials were "target trials" with a valid cue followed by a valid probe X. This feature was intended to encourage participants to "expect" a valid probe to follow a valid cue. A consequence of this manipulation was that participants developed a prepotency to respond with "target" responses on trials for which valid cues were presented. The cue was presented for 1000msec, the inter-stimulus interval was 2000msec, and the target was presented for 500msec with a response window of 1500msec. The ITI was 1200msec. Participants had to practice until criteria were obtained. In the AX-CPT task, the subjects were instructed to press the "Yes" button every time there is a blue letter 'X' (target) following a white letter 'A' (cue). During this task, any letter appears on the screen randomly. The value calculated was the rate of correct response for all the reaction of target trial.
Measured: 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
The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Total Score
The PANSS consisted of 3 subscales containing 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. PANSS Positive and Negative subscale scores symptom constructs consisted of positive subscale (7 positive symptom constructs), negative subscale (7 negative symptom constructs), and general psychopathology subscale (16 symptom constructs). The possible maximum PANSS total score was 210; 30 indicating no symptoms; 210 indicating extremely severe symptoms.
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in PANSS Positive Subscale Score
PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Positive Subscale Score
PANSS consisted of positive subscales with 7 symptom constructs (delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in PANSS Negative Subscale Score
PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Negative Subscale Score
PANSS consisted of negative subscale with 7 symptom constructs (blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation, and stereotyped thinking). Each item was scored using a scale of 1 to 7 (a higher score indicated increased severity). The maximum subscale score was 49; 7 indicated no symptoms; 49 indicated extreme severity.
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score
The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in CGI-S Score
The severity of illness for each participant was assessed. The rater or investigator's response choices included: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants.
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6
To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's 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. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).
Measured: During trial visits from Day 0 to Week 6 (Day 42).
CGI-I Score at Week 3
To assess whether the total improvement was entirely due to drug treatment. The rater or investigator's 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. The response at a given week was compared to the participant's condition at baseline (last available measurement at the baseline/Day 0 visit before the first dose of IMP).
Measured: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)
A validated clinician-rated scale that measured personal and social functioning in 4 domains: socially useful activities (eg, work and study), personal and social relationships, self-care, and disturbing and aggressive behaviors. Impairment was rated as absent, mild, manifest, marked, severe, or very severe and were converted to a total score on a 100-point scale: 71 to 100 - mild functional difficulty, 31 to 70 - manifest disabilities of various degrees and 1 to 30 - minimal functioning that required intense support and/or supervision.
Measured: During trial visits from Day 0 to Week 6 (Day 42).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study startFeb 2015
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Schizophrenia With ImpulsivityStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Otsuka Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02194933
- Sponsor's protocol ID
- 331-13-009
- Status last verified
- Oct 2018
- First submitted
- 16 Jul 2014
- Last updated
- 8 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
van Erp TG, Baker RA, Cox K, Okame T, Kojima Y, Eramo A, Potkin SG. Effect of brexpiprazole on control of impulsivity in schizophrenia: A randomized functional magnetic resonance imaging study. Psychiatry Res Neuroimaging. 2020 Jul 30;301:111085. doi: 10.1016/j.pscychresns.2020.111085. Epub 2020 May 5.
PubMed 32450497
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02194933
- Acronym / sponsor ID
- 331-13-009
- Conditions
- Schizophrenia With Impulsivity
- Keywords
- Schizophrenia, Mental Disorders, Antipsychotic,, Psychotic disorder, Impulsivity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Otsuka Pharmaceutical Co., Ltd.
- Study start
- Feb 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 21 Jul 2014 (estimated)
- Results
- Posted 11 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brexpiprazole 2 mg | Experimental | Drug: BrexpiprazoleBrexpiprazole 2 mg/day, once daily dose, tablet, orally |
| Brexpiprazole 4 mg | Experimental | Drug: BrexpiprazoleBrexpiprazole 4 mg/day, once daily dose, tablet, orally |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrexpiprazoleAlso: OPC-34712Brexpiprazole 2 mg/day, once daily dose, tablet, orally, for 6 weeks - Brexpiprazole 4 mg/day, once daily dose, tablet, orally, for 6 weeks | Drug | Brexpiprazole 2 mg, Brexpiprazole 4 mg |
Primary outcome
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.
22 secondary outcomes
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)
Time frame: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
Change From Baseline to Week 6 in Barratt Impulsiveness Scale (BIS-11)
Time frame: At baseline (Day 0), and Week 6 (Day 42) of the treatment.
Change From Baseline to Week 3 in BIS-11
Time frame: At baseline (Day 0), and Week 3 (Day 21) of the treatment.
Change From Baseline to Week 6 in Go/No-go Task Behavior
Time frame: At baseline (Day 0), week 6 (Day 42) of the treatment phase
Change From Baseline to Week 3 in Go/No-go Task Behavior
Time frame: At baseline (Day 0), and week 3 (Day 21) of the treatment phase
Change From Baseline to Week 6 in Monetary Choice Questionnaire (MCQ) Score
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in MCQ Score
Time frame: 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
Time frame: At baseline (Day 0), and Week 6 (Day 42).
Change From Baseline to Week 3 in SSRT Task Behavior
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Continuous Performance Task (CPT) Behavior
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in CPT Behavior
Time frame: 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
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Total Score
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in PANSS Positive Subscale Score
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Positive Subscale Score
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in PANSS Negative Subscale Score
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in PANSS Negative Subscale Score
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Change From Baseline to Week 3 in CGI-S Score
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Clinical Global Impression - Improvement Scale (CGI-I) Score at Week 6
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
CGI-I Score at Week 3
Time frame: During trial visits from Day 0 to Week 3 (Day 21).
Change From Baseline to Week 6 in Personal and Social Performance Scale (PSP)
Time frame: During trial visits from Day 0 to Week 6 (Day 42).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32450497van Erp TG, Baker RA, Cox K, Okame T, Kojima Y, Eramo A, Potkin SG. Effect of brexpiprazole on control of impulsivity in schizophrenia: A randomized functional magnetic resonance imaging study. Psychiatry Res Neuroimaging. 2020 Jul 30;301:111085. doi: 10.1016/j.pscychresns.2020.111085. Epub 2020 May 5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brexpiprazole in people with Schizophrenia With Impulsivity, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02194933, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2018.