A Phase 3 interventional study of Brexpiprazole and Placebo in Bipolar I Disorder and Manic Episode, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 38 sites in 3 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-02-11.
Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. (part of Otsuka Holdings Co., Ltd.) · Phase 3, Interventional, and Treatment
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.
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).
166 studies on the registry are indexed under Mania; 13 are open to participants now.
This study's enrollment of 333 is above the median of 89 across 138 interventional studies indexed under Mania.
Browse Mania studies →Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 295 studies on the registry; 18 are open to participants now.
Of its 106 completed or terminated interventional studies of FDA-regulated products, 71 (67%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Matching placebo was administered in the same way as brexpiprazole to maintain the blind
Drug: Placebo
Brexpiprazole was administered orally with flexible dosing from 2 to 4 mg/day; titrated to a maximum of 4 mg/day for 3 weeks.
Administered orally daily for 3 weeks.
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).
Time frame: Baseline, Week 3
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.
Time frame: Baseline, Week 3
| Milestone | Brexpiprazole | Placebo |
|---|---|---|
| Started | 163 | 170 |
| Received at least 1 dose of study drug | 162 | 170 |
| Completed | 128 | 135 |
| Not completed | 35 | 35 |
| Withdrew: Adverse event | 4 | 8 |
| Withdrew: Lack of efficacy | 1 | 2 |
| Withdrew: Non-compliance with study drug | 0 | 2 |
| Withdrew: Withdrawal by subject | 23 | 17 |
| Withdrew: Physician decision | 3 | 1 |
| Withdrew: Other | 0 | 1 |
| Withdrew: Lost to follow-up | 4 | 4 |
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).
| units on a scale | Brexpiprazole | Placebo |
|---|---|---|
| Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3 | -12.3 ± 0.73 | -10.7 ± 0.71 |
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.
| units on a scale | Brexpiprazole | Placebo |
|---|---|---|
| Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3 | -1.31 ± 1.22 | -1.06 ± 1.09 |
Collected over From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).. Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Brexpiprazole | 0/162 (0%) | 0/162 (0%) | 32/162 (19.8%) |
| Placebo | 0/170 (0%) | 3/170 (1.8%) | 28/170 (16.5%) |
| Event | Brexpiprazole | Placebo |
|---|---|---|
| ManiaPsychiatric disorders | 0/162 | 2/170 |
| EpilepsyNervous system disorders | 0/162 | 1/170 |
| Event | Brexpiprazole | Placebo |
|---|---|---|
| HeadacheNervous system disorders | 10/162 | 18/170 |
| AkathisiaNervous system disorders | 13/162 | 4/170 |
| NauseaGastrointestinal disorders | 2/162 | 7/170 |
| ConstipationGastrointestinal disorders | 6/162 | 5/170 |
| DizzinessNervous system disorders | 5/162 | 1/170 |
| InsomniaPsychiatric disorders | 5/162 | 2/170 |
The baseline population consisted of all randomized participants.
| Age, Continuous(Years) | Brexpiprazole | Placebo | Total |
|---|---|---|---|
| Mean | 44.6 ± 10.7 | 44.3 ± 12.0 | 44.5 ± 11.4 |
| Sex: Female, Male(Participants) | Brexpiprazole | Placebo | Total |
|---|---|---|---|
| Female | 85 | 82 | 167 |
| Male | 78 | 88 | 166 |
| Race/Ethnicity, Customized(Participants) | Brexpiprazole | Placebo | Total |
|---|---|---|---|
| White | 90 | 102 | 192 |
| Black or African American | 70 | 67 | 137 |
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Other Race | 2 | 1 | 3 |
| Race/Ethnicity, Customized(Participants) | Brexpiprazole | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 22 | 17 | 39 |
| Not Hispanic or Latino | 140 | 153 | 293 |
| Other Ethnicity | 1 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report
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
Ran from Sep 2017 to primary completion in Jan 2019, 16 months.
Results were first posted in Jan 2020, 11 months after primary completion.
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Studies of the drug tested here: Brexpiprazole
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