A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder
A Multicenter, Randomized, Double-blind Trial of Brexpiprazole Versus Placebo for the Acute Treatment Manic Episodes, With or Without Mixed Features, Associated With Bipolar I Disorder
1 other identifier
interventional
333
3 countries
38
Brief Summary
To demonstrate the efficacy of brexpiprazole for the acute treatment of manic episodes, with or without mixed features, in participants with a diagnosis of bipolar I disorder.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2017
Shorter than P25 for phase_3
38 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 4, 2017
CompletedFirst Posted
Study publicly available on registry
August 22, 2017
CompletedStudy Start
First participant enrolled
September 19, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 22, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 22, 2019
CompletedResults Posted
Study results publicly available
January 2, 2020
CompletedFebruary 11, 2020
February 1, 2020
1.3 years
August 4, 2017
December 13, 2019
February 3, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
The YMRS was utilized to assess a participant's level of manic symptoms. It consists of 11 items: 1) elevated mood, 2) increased motor activity-energy, 3) sexual interest, 4) sleep, 5) irritability, 6) speech (rate and amount), 7) language-thought disorder, 8) content, 9) disruptive-aggressive behavior, 10) appearance, and 11) insight. Seven items are rated on a 0- to 4-scale, while four items (Items 5, 6, 8, and 9) are rated on a 0- to 8-scale with 0, 2, 4, 6, and 8 being the possible scores (twice the weight of the other items). For all items, 0 is the "best" rating and the highest score (4 or 8) is the 'worst' rating. The YMRS total score is the sum of ratings for all 11 items; therefore, possible total scores range from 0 to 60, with higher scores signifying more severe manic symptoms. Comparison between treatment groups was carried out using mixed-effect model repeated measure (MRMM).
Baseline, Week 3
Secondary Outcomes (1)
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
Baseline, Week 3
Study Arms (2)
Brexpiprazole
EXPERIMENTALParticipants received a starting dose of 2 milligrams (mg)/day brexpiprazole from Days 1 to 3, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4.
Placebo
PLACEBO COMPARATORMatching placebo was administered in the same way as brexpiprazole to maintain the blind
Interventions
Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.
Eligibility Criteria
You may qualify if:
- Male or female participants, ages 18 to 65 years, inclusive, at the time of informed consent.
- Participants willing to discontinue all prohibited medications to meet protocol-required washouts prior to and during the trial period.
- Participants with a Diagnostic \& Statistical Manual on Mental Disorders, 5th Edition (DSM-5) diagnosis of bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization. Diagnosis confirmed by the MINI International Neuropsychiatric Interview (MINI) and a history of at least one previous manic episode with or without mixed features with manic symptoms of sufficient severity to require one of the following interventions: hospitalization or treatment with a mood stabilizer, or treatment with an antipsychotic agent. "Require" was defined as an intervention that occurred rather than one that was recommended.
- Young-mania rating scale (YMRS) score of ≥ 24 at screening and baseline
You may not qualify if:
- Sexually active male or women of childbearing potential (WOCBP) who did not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP).
- Females who were breastfeeding and/or who had a positive pregnancy test result prior to receiving trial medication.
- Participants considered unresponsive to clozapine or who were only responsive to clozapine.
- Participants with a history of DSM-5 diagnosis other than bipolar I disorder, including schizophrenia, schizoaffective disorder, major depressive disorder, attention-deficit/hyperactivity disorder, delirium, dementia, amnestic, or other cognitive disorders. Also, participants with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder. All other current diagnoses must have been discussed with the medical monitor.
- Participants whose current manic episode had lasted for more than 4 weeks overall, or who had required hospitalization \> 21 days for the current acute episode at the time of the screening visit, excluding hospitalization for psychosocial reasons.
- Participant with manic symptoms better accounted for by another general medical condition or direct physiological effect of substance (for example, medications).
- Participants who have had electroconvulsive treatment within the past 2 months.
- Participants with a positive drug screen for cocaine or other illicit drugs.
- Abnormal laboratory test results, vital signs or electrocardiogram findings, unless, based on investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.
- Rapid cyclers with more than 6 episodes in the previous year.
- Participants with hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days) or an abnormal result for free thyroxine at screening.
- Participants with uncontrolled hypertension or symptomatic hypotension or orthostatic hypotension.
- Participants with epilepsy or history of seizures.
- Participants who participated in a clinical trial within the last 60 days or who participated in more than 2 clinical trials within the past year.
- Use of psychotropic medications (other than benzodiazepines) within 7 days of the baseline YMRS.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (38)
Atria Clinical Research
Little Rock, Arkansas, 72209, United States
Woodland International Research Group, LLC
Little Rock, Arkansas, 72211, United States
CiTrials
Bellflower, California, 90706, United States
CNS Research Science Inc.
Cerritos, California, 90703, United States
Apostle Clinical Trials
Long Beach, California, 90813, United States
CNRI-San Diego
San Diego, California, 92102, United States
Artemis Institute for Clinical Research
San Diego, California, 92103, United States
CiTrials
Santa Ana, California, 92705, United States
Collaborative Neuroscience Network, LLC
Torrance, California, 90502, United States
Shreenath Clinical Service
Yorba Linda, California, 92886, United States
Galiz Research
Hialeah, Florida, 33016, United States
Research Centers of America LLC
Hollywood, Florida, 33024, United States
Optimus U Corporation
Miami, Florida, 33125, United States
South Florida Research Phase I-IV
Miami Springs, Florida, 33166, United States
Meridien Research
Orlando, Florida, 32801, United States
iResearch Atlanta, LLC
Decatur, Georgia, 30030, United States
Uptown Research Institute LLC
Chicago, Illinois, 60640, United States
Neuropsychiatric Research & Associates, LTD
Winfield, Illinois, 60190, United States
Louisiana Clinical Research
Shreveport, Louisiana, 71101, United States
Arch Clinical Trials, LLC
St Louis, Missouri, 63118, United States
St Louis Clinical Trials LLC
St Louis, Missouri, 63141, United States
Hassman Research Institute
Berlin, New Jersey, 08009, United States
CNS Research Science, Inc.
Jamaica, New York, 11432, United States
New Hope Clinical Research
Charlotte, North Carolina, 28211, United States
University of Cincinnati Department of Psychiatry and Behavorial Science
Cincinnati, Ohio, 45219, United States
InSite Clinical Research LLC
DeSoto, Texas, 75115, United States
Pillar Clinical Research, LLC
Richardson, Texas, 75080, United States
Clinical Hospital Centre Rijeka
Rijeka, 51000, Croatia
Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov
Dnipro, 49005, Ukraine
SI ""Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Sciences of Ukraine
Kharkiv, 61068, Ukraine
Communal Establishment "Kherson Regional Psychiatric Hospital" of Kherson Regional Council
Kherson, 73488, Ukraine
Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic disorders
Kyiv, 04080, Ukraine
Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #20
Lviv, 79021, Ukraine
Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #25
Lviv, 79021, Ukraine
Communal Establishment "Odesa Regional Psychiatric Hospital #2
Oleksandrivka, 67513, Ukraine
O.F. Maltsev Poltava Regional Psychiatric Hospital
Poltava, 36013, Ukraine
Ternopil Regional Municipal Clinical Psychoneurolgical Hospital
Ternopil, 46027, Ukraine
Communal Establishment "Acad. O.I. Iushchenko Vinnytsia Regional Psychoneurologic Hospital"
Vinnytsia, 21005, Ukraine
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Development
- Organization
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Officials
- STUDY DIRECTOR
Matthew Leoni, M.D.
Otsuka Pharmaceutical Development & Commercialization, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 4, 2017
First Posted
August 22, 2017
Study Start
September 19, 2017
Primary Completion
January 22, 2019
Study Completion
January 22, 2019
Last Updated
February 11, 2020
Results First Posted
January 2, 2020
Record last verified: 2020-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
- Access Criteria
- Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.