Bipolar I DisorderPhase 3NCT03259555
A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder
A Phase 3 study testing Brexpiprazole in people with Bipolar I Disorder and Manic Episode, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 48 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar I Disorder, Manic Episode
- What is being tested?
- Brexpiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 322 participants
- Where
- 48 sitesin 4 countries
- Study dates
- 14 Sep 2017to 2 Jan 2019
- 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
- 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.
Who cannot join
- 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).
Show all 17Show fewer
- 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.
- 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).
Trial locations and contacts
48 sites in 4 countries.
48 sites in 4 countries
United States29 sites
Radiant Research Inc.
Atlanta, Georgia, 30325
University of Texas at Austin
Austin, Texas, 78712
Community Clinical Research, Inc.
Austin, Texas, 78754
Carolina Clinical Trials, Inc.
Charleston, South Carolina, 29407
ProScience Research Group
Culver City, California, 90230
CBH Health
Gaithersburg, Maryland, 20877
Collaborative Neuroscience Network, LLC
Garden Grove, California, 92845
Pillar Clinical Research, LLC
Garland, Texas, 75042
Behavioral Research Specialists, LLC
Glendale, California, 91206
Galiz Research
Hialeah, Florida, 33016
Alexian Brothers Center for Psychiatric Research
Hoffman Estates, Illinois, 60169
Advanced Research Institute of Miami
Homestead, Florida, 33030
Florida Behavioral Medicine
Largo, Florida, 33770
Woodland International Research Group
Little Rock, Arkansas, 72211
Optimus U Corporation
Miami, Florida, 33125
Behavioral Clinical Research, Inc.
North Miami, Florida, 33161
Segal Trials
North Miami, Florida, 33161
Pacific Research Partners, LLC
Oakland, California, 94607
SP Research PLLC
Oklahoma City, Oklahoma, 73112
Cutting Edge Research Group
Oklahoma City, Oklahoma, 73116
NRC Research Institute
Orange, California, 92868
Asclepes Research Centers
Panorama City, California, 91402
Richard H Weisler, MD, PA, and Associates
Raleigh, North Carolina, 27609
Pillar Clinical Research, LLC
Richardson, Texas, 75080
Mid Columbia Research
Richland, Washington, 99352
Ci Trials
Riverside, California, 92506
Woodland Research Northwest, LLC
Rogers, Arkansas, 72758
Sharp Vista Hospital
San Diego, California, 92123
Advanced Clinical Research Center, LLC
St Louis, Missouri, 63123
Bulgaria9 sites
Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD
Burgas, 8000
State Psychiatry Hospital - Kardzhali
Kardzhali, 6600
State Psychiatry Hospital Sv. Ivan Rilski
Novi Iskar, 1282
University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
Plovdiv, 4002
Mental Health Center - Ruse EOOD
Rousse, 7003
University Multiprofile Hospital for Active Treatment Alexandrovska EAD
Sofia, 1431
Multiprofile Hospital for Active Treatment - Targovishte AD
Targovishte, 7700
Mental Health Center - Veliko Tarnovo EOOD
Veliko Tarnovo, 5000
Mental Health Center - Vratsa EOOD
Vratsa, 3000
Serbia6 sites
Clinic for Psychiatric Disorders Dr Laza Lazarevic
Belgrade, 11000
Clinical Center of Serbia
Belgrade, 11000
Clinical Hospital Center Dr Dragisa Misovic-Dedinje
Belgrade, 11000
Special Hospital for Psychiatric Diseases Kovin
Kovin, 26220
Clinical Center Kragujevac
Kragujevac, 34000
Clinical Center of Vojvodina
Novi Sad, 21000
Poland4 sites
Samodzielny Publiczny Psychiatryczny Zaklad Opieki Zdrowotnej im. Dr. Stanislawa Deresza w Choroszczy
Choroszcz, 16-070
Uniwersyteckie Centrum Kliniczne w Gdansku Klinika Psychiatrii Doroslych
Gdansk, 80-952
NZOZ Centrum Medyczne HCP Sp. z o. o.
Poznan, 61-485
NZOZ Prywatna Klinika Psychiatryczna Inventiva
Tuszyn, 95-080
About this study
Official title: 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
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.
Read the 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).
- Conditions
- Bipolar I Disorder, Manic Episode
- Being tested
- Brexpiprazole, Placebo
- Keywords
- Brexpiprazole, Bipolar, Manic episode
- Medical subject headings
- Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.
PlaceboDrug
Administered orally daily for 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Brexpiprazole | Experimental | 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. Receives: Drug: Brexpiprazole |
| Placebo | Placebo comparator | Matching placebo was administered in the same way as brexpiprazole to maintain the blind. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline, Week 3
Secondary outcomes (1)
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At 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.
Measured: Baseline, Week 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2017
- Study start14 Sep 2017
- Primary completion2 Jan 2019
- Study completion2 Jan 2019
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.
- Other trials for Bipolar I DisorderStudies 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
- Model description
- Participants received a dose of brexpiprazole or placebo for a maximum of 21 days and were evaluated throughout the duration of the study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 322 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Responsible party
- Sponsor
- Investigators
- Matthew Leoni, M.D., Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03259555
- Sponsor's protocol ID
- 331-201-00080
- Status last verified
- Feb 2020
- First submitted
- 4 Aug 2017
- Last updated
- 10 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03259555
- Acronym / sponsor ID
- 331-201-00080
- Conditions
- Bipolar I Disorder, Manic Episode
- Keywords
- Brexpiprazole, Bipolar, Manic episode
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 322 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lundbeck A/S
- Study start
- 14 Sep 2017 (actual)
- Primary completion
- 2 Jan 2019 (actual)
- Study completion
- 2 Jan 2019 (actual)
- First posted
- 23 Aug 2017 (actual)
- Results
- Posted 10 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants received a dose of brexpiprazole or placebo for a maximum of 21 days and were evaluated throughout the duration of the study.
| Arm | Type | Receives |
|---|---|---|
| Brexpiprazole | Experimental | Drug: BrexpiprazoleParticipants 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 comparator | Drug: PlaceboMatching placebo was administered in the same way as brexpiprazole to maintain the blind. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| BrexpiprazoleBrexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks. | Drug | Brexpiprazole |
| PlaceboAdministered orally daily for 3 weeks. | Drug | Placebo |
Primary outcome
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 (MMRM).
1 secondary outcome
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
Time frame: Baseline, Week 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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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.
Matthew Leoni, M.D. study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
48 sites in 4 countries: 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 Bipolar I Disorder and Manic Episode, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 48 sites in 4 countries.
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 4 inclusion and 17 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 10 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in United States, Bulgaria, Serbia, Poland. 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. Some participants in this study may receive a placebo. 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 10 Feb 2020). 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 In Young-Mania Rating Scale (YMRS) Score At Week 3 (time frame: Baseline, Week 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2020.