A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder

February 3, 2020 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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. This study also demonstrated the safety and tolerability of brexpiprazole in the study population of males and females aged 18 to 65 years (inclusive, at time of consent).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
333

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
      • Rijeka, Croatia, 51000
        • Clinical Hospital Centre Rijeka
  • Ukraine
      • Dnipro, Ukraine, 49005
        • Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnikov
      • Kharkiv, Ukraine, 61068
        • SI ""Institute of Neurology, Psychiatry and Narcology of National Academy of Medical Sciences of Ukraine
      • Kherson, Ukraine, 73488
        • Communal Establishment "Kherson Regional Psychiatric Hospital" of Kherson Regional Council
      • Kyiv, Ukraine, 04080
        • Kyiv Regional Medical Incorporation "Psychiatry", Center for Novel Treatment and Rehabilitation of Psychotic Disorders
      • Lviv, Ukraine, 79021
        • Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #20
      • Lviv, Ukraine, 79021
        • Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", Department #25
      • Oleksandrivka, Ukraine, 67513
        • Communal Establishment "Odesa Regional Psychiatric Hospital #2
      • Poltava, Ukraine, 36013
        • O.F. Maltsev Poltava Regional Psychiatric Hospital
      • Ternopil', Ukraine, 46027
        • Ternopil Regional Municipal Clinical Psychoneurolgical Hospital
      • Vinnytsia, Ukraine, 21005
        • Communal Establishment "Acad. O.I. Iushchenko Vinnytsia Regional Psychoneurologic Hospital"
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Woodland International Research Group, LLC
      • Little Rock, Arkansas, United States, 72209
        • Atria Clinical Research
    • California
      • Bellflower, California, United States, 90706
        • CiTrials
      • Cerritos, California, United States, 90703
        • CNS Research Science Inc.
      • Long Beach, California, United States, 90813
        • Apostle Clinical Trials
      • San Diego, California, United States, 92102
        • Cnri-San Diego
      • San Diego, California, United States, 92103
        • Artemis Institute for Clinical Research
      • Santa Ana, California, United States, 92705
        • CiTrials
      • Torrance, California, United States, 90502
        • Collaborative Neuroscience Network, LLC
      • Yorba Linda, California, United States, 92886
        • Shreenath Clinical Service
    • Florida
      • Hialeah, Florida, United States, 33016
        • Galiz Research
      • Hollywood, Florida, United States, 33024
        • Research Centers of America LLC
      • Miami, Florida, United States, 33125
        • Optimus U Corporation
      • Miami Springs, Florida, United States, 33166
        • South Florida Research Phase I-IV
      • Orlando, Florida, United States, 32801
        • Meridien Research
    • Georgia
      • Decatur, Georgia, United States, 30030
        • iResearch Atlanta, LLC
    • Illinois
      • Chicago, Illinois, United States, 60640
        • Uptown Research Institute LLC
      • Winfield, Illinois, United States, 60190
        • Neuropsychiatric Research & Associates, LTD
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Louisiana Clinical Research
    • Missouri
      • Saint Louis, Missouri, United States, 63118
        • Arch Clinical Trials, LLC
      • Saint Louis, Missouri, United States, 63141
        • St Louis Clinical Trials LLC
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Hassman Research Institute
    • New York
      • Jamaica, New York, United States, 11432
        • CNS Research Science, Inc.
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
        • New Hope Clinical Research
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Department of Psychiatry and Behavorial Science
    • Texas
      • DeSoto, Texas, United States, 75115
        • InSite Clinical Research LLC
      • Richardson, Texas, United States, 75080
        • Pillar Clinical Research, LLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
  • Participants who currently had clinically significant neurological, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders
  • Participants who received brexpiprazole in any prior clinical trial or currently taking commercially available brexpiprazole (Rexulti).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Brexpiprazole
Participants 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.
Drug: Brexpiprazole
Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.
Placebo Comparator: Placebo
Matching placebo was administered in the same way as brexpiprazole to maintain the blind
Drug: Placebo
Administered orally daily for 3 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
Time Frame: Baseline, 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
Time Frame: Baseline, Week 3
The CGI-BP scale refers to the global impression of the participant with respect to bipolar disorder. The scale rates the participant's severity of illness (CGI-BP severity of illness: mania, depression, and overall bipolar illness) based on a 7-point scale: 1 = normal, not at all ill, 2 = minimally ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = very severely ill.
Baseline, Week 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
H. Lundbeck A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Matthew Leoni, M.D., Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 19, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 22, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 22, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 22, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 11, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 331-201-00081

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing 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.

IPD Sharing 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

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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