A Phase 3 interventional study of Brexpiprazole in Bipolar I Disorder and Acute Mania, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 73 sites in 6 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-08-17.
Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. · Phase 3, Interventional, and Treatment
This study evaluated the safety and evaluate the safety and tolerability of open-label brexpiprazole (2 - 4 mg/day, with a starting dose of 2 mg/day) for the treatment of adult subjects with bipolar I disorder. All participants received a starting dose of brexpiprazole.
While the availability of atypical antipsychotics had increased the therapeutic options available, there remains a need for safer and more effective therapies in the treatment of manic and depressive episodes of bipolar I disorder. Brexpiprazole's specific receptor activity profile likely correlates with its established efficacy in schizophrenia and major depressive disorder, and may prove to be an effective target for the treatment of acute mania of bipolar I disorder.
Inclusion Criteria (rollover participants from 331-201-00080 \& 331-201-00081 trials)
Exclusion Criteria (rollover participants from 331-201-00080 \& 331-201-00081 trials)
Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, 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 tablets
Also known as: OPC-34712
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.
Time frame: From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
| Milestone | Prior Brexpiprazole | Prior Placebo |
|---|---|---|
| Started | 188 | 193 |
| Analyzed for safety (safety sample) | 184 | 184 |
| Completed | 105 | 100 |
| Not completed | 83 | 93 |
| Withdrew: Adverse event | 14 | 12 |
| Withdrew: Lack of efficacy | 1 | 0 |
| Withdrew: Lost to follow-up | 13 | 19 |
| Withdrew: Non-compliance with study drug | 5 | 9 |
| Withdrew: Progressive disease | 1 | 0 |
| Withdrew: Protocol deviation | 2 | 1 |
| Withdrew: Withdrawal by subject | 36 | 43 |
| Withdrew: Early closure of the site | 0 | 1 |
| Withdrew: Physician decision | 5 | 5 |
| Withdrew: Reason not specified | 6 | 3 |
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, and 3 = severe; inability to work or perform normal daily activity.
| Participants | Prior Brexpiprazole | Prior Placebo |
|---|---|---|
| TEAE, Any grade | 79 | 86 |
| TEAE, Mild | 60 | 68 |
| TEAE, Moderate | 31 | 29 |
| TEAE, Severe | 8 | 5 |
Collected over From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Prior Brexpiprazole | 0/184 (0%) | 11/184 (6%) | 13/184 (7.1%) |
| Prior Placebo | 0/184 (0%) | 8/184 (4.3%) | 26/184 (14.1%) |
| Event | Prior Brexpiprazole | Prior Placebo |
|---|---|---|
| ManiaPsychiatric disorders | 5/184 | 1/184 |
| DepressionPsychiatric disorders | 3/184 | 2/184 |
| Acute Myocardial InfarctionCardiac disorders | 0/184 | 1/184 |
| Vertigo PositionalEar and labyrinth disorders | 0/184 | 1/184 |
| Upper Gastrointestinal HaemorrhageGastrointestinal disorders | 1/184 | 0/184 |
| Chest PainGeneral disorders | 0/184 | 1/184 |
| CellulitisInfections and infestations | 1/184 | 0/184 |
| MigraineNervous system disorders | 0/184 | 1/184 |
| Bipolar DisorderPsychiatric disorders | 0/184 | 1/184 |
| Suicidal BehaviourPsychiatric disorders | 1/184 | 0/184 |
| Event | Prior Brexpiprazole | Prior Placebo |
|---|---|---|
| AkathisiaNervous system disorders | 8/184 | 17/184 |
| HeadacheNervous system disorders | 5/184 | 10/184 |
Enrolled Sample included all participants who signed an inform consent form (ICF) for the trial.
| Age, Continuous(years) | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Mean | 45.6 ± 11.0 | 46.1 ± 11.5 | 45.8 ± 11.2 |
| Sex: Female, Male(Participants) | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Female | 97 | 92 | 189 |
| Male | 91 | 101 | 192 |
| Race/Ethnicity, Customized(Participants) | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Race — White | 129 | 146 | 275 |
| Race — Black or African American | 52 | 47 | 99 |
| Race — American Indian or Alaska Native | 3 | 0 | 3 |
| Race — Asian | 2 | 0 | 2 |
| Race — Race-Other | 2 | 0 | 2 |
| Race/Ethnicity, Customized(Participants) | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Ethnicity — Hispanic or Latino | 21 | 24 | 45 |
| Ethnicity — Not Hispanic or Latino | 165 | 169 | 334 |
| Ethnicity — Ethnicity-Other | 2 | 0 | 2 |
Documents are hosted by the registry — open the source record to download them.
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, Sap, Csr
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Otsuka Pharmaceutical Development & Commercialization, Inc.