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 of Manic Episodes, With or Without Mixed Features, Associated With Bipolar I Disorder
1 other identifier
interventional
322
4 countries
48
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
48 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 23, 2017
CompletedStudy Start
First participant enrolled
September 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 2, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 2, 2019
CompletedResults Posted
Study results publicly available
February 10, 2020
CompletedFebruary 10, 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 (MMRM).
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 and a history of at least 1 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 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.
- 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, medication).
- 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 or 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.
- Participant 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 (48)
Woodland International Research Group
Little Rock, Arkansas, 72211, United States
Woodland Research Northwest, LLC
Rogers, Arkansas, 72758, United States
ProScience Research Group
Culver City, California, 90230, United States
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845, United States
Behavioral Research Specialists, LLC
Glendale, California, 91206, United States
Pacific Research Partners, LLC
Oakland, California, 94607, United States
NRC Research Institute
Orange, California, 92868, United States
Asclepes Research Centers
Panorama City, California, 91402, United States
Ci Trials
Riverside, California, 92506, United States
Sharp Vista Hospital
San Diego, California, 92123, United States
Galiz Research
Hialeah, Florida, 33016, United States
Advanced Research Institute of Miami
Homestead, Florida, 33030, United States
Florida Behavioral Medicine
Largo, Florida, 33770, United States
Optimus U Corporation
Miami, Florida, 33125, United States
Behavioral Clinical Research, Inc.
North Miami, Florida, 33161, United States
Segal Trials
North Miami, Florida, 33161, United States
Radiant Research Inc.
Atlanta, Georgia, 30325, United States
Alexian Brothers Center for Psychiatric Research
Hoffman Estates, Illinois, 60169, United States
CBH Health
Gaithersburg, Maryland, 20877, United States
Advanced Clinical Research Center, LLC
St Louis, Missouri, 63123, United States
Richard H Weisler, MD, PA, and Associates
Raleigh, North Carolina, 27609, United States
SP Research PLLC
Oklahoma City, Oklahoma, 73112, United States
Cutting Edge Research Group
Oklahoma City, Oklahoma, 73116, United States
Carolina Clinical Trials, Inc.
Charleston, South Carolina, 29407, United States
University of Texas at Austin
Austin, Texas, 78712, United States
Community Clinical Research, Inc.
Austin, Texas, 78754, United States
Pillar Clinical Research, LLC
Garland, Texas, 75042, United States
Pillar Clinical Research, LLC
Richardson, Texas, 75080, United States
Mid Columbia Research
Richland, Washington, 99352, United States
Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD
Burgas, 8000, Bulgaria
State Psychiatry Hospital - Kardzhali
Kardzhali, 6600, Bulgaria
State Psychiatry Hospital Sv. Ivan Rilski
Novi Iskar, 1282, Bulgaria
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
Plovdiv, 4002, Bulgaria
Mental Health Center - Ruse EOOD
Rousse, 7003, Bulgaria
University Multiprofile Hospital for Active Treatment Alexandrovska EAD
Sofia, 1431, Bulgaria
Multiprofile Hospital for Active Treatment - Targovishte AD
Targovishte, 7700, Bulgaria
Mental Health Center - Veliko Tarnovo EOOD
Veliko Tarnovo, 5000, Bulgaria
Mental Health Center - Vratsa EOOD
Vratsa, 3000, Bulgaria
Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej im. Dr. Stanislawa Deresza w Choroszczy
Choroszcz, 16-070, Poland
Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Psychiatrii Doroslych
Gdansk, 80-952, Poland
NZOZ Centrum Medyczne HCP Sp. z o. o.
Poznan, 61-485, Poland
NZOZ Prywatna Klinika Psychiatryczna Inventiva
Tuszyn, 95-080, Poland
Clinic for Psychiatric Disorders Dr Laza Lazarevic
Belgrade, 11000, Serbia
Clinical Center of Serbia
Belgrade, 11000, Serbia
Clinical Hospital Center Dr Dragisa Misovic-Dedinje
Belgrade, 11000, Serbia
Special Hospital for Psychiatric Diseases Kovin
Kovin, 26220, Serbia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
Clinical Center of Vojvodina
Novi Sad, 21000, Serbia
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 23, 2017
Study Start
September 14, 2017
Primary Completion
January 2, 2019
Study Completion
January 2, 2019
Last Updated
February 10, 2020
Results First Posted
February 10, 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.