Acute Mania, Bipolar I Disorder
Conditions
Keywords
Bipolar, Mania, Brexpiprazole
Brief summary
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.
Detailed description
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.
Interventions
DRUGBrexpiprazole
Brexpiprazole tablets
Sponsors
H. Lundbeck A/S
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Group composed of eligible rollover participants who completed one of the double-blind, phase 3 efficacy trials (331-201-00080 (NCT03259555) or 331-201-00081 (NCT03257865)).
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
(rollover participants from 331-201-00080 & 331-201-00081 trials) * Participants remaining in hospital at the Day 21 visit of trial 331-201-00080 or 331-201-00081 were permitted to enroll in the 331-201-00083 trial at the week 3 visit of the double-blind trial if they were planned to be discharged from the hospital before the week 1 visit of trial 331-201-0083. Participants not discharged by the week 1 visit of trial 331-201-0083 were withdrawn. * Participants who, in the opinion of the investigator, could potentially benefit from administration of oral brexpiprazole for the treatment of bipolar I disorder and who completed 3 weeks of post-randomization treatment in Trial 331-201-00080 & Trial 331-201-00081.
Exclusion criteria
(rollover participants from 331-201-00080 & 331-201-00081 trials) * Participants with a major protocol violation during the course of their participation in the double-blind phase 3 trials (331-201-00080 or 331-201-00081).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up) | 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. |
Countries
Bulgaria, Croatia, Poland, Serbia, Ukraine, United States
Participant flow
Pre-assignment details
The study included participants who completed 3-week double-blind treatment in studies 331-201-00080 (NCT03259555)/331-201-00081 (NCT03257865) and, who in the investigator's judgment, could potentially benefit to receive brexpiprazole in this study. Data was summarized as per the treatment received in the previous studies.
Participants by arm
| Arm | Count |
|---|---|
| Prior Brexpiprazole 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. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group. | 188 |
| Prior Placebo 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. Participants who received placebo in the double-blind treatment period in previous studies were included in this group. | 193 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 12 |
| Overall Study | Early Closure of the Site | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 13 | 19 |
| Overall Study | Non-Compliance With Study Drug | 5 | 9 |
| Overall Study | Physician Decision | 5 | 5 |
| Overall Study | Progressive Disease | 1 | 0 |
| Overall Study | Protocol Deviation | 2 | 1 |
| Overall Study | Reason not Specified | 6 | 3 |
| Overall Study | Withdrawal by Subject | 36 | 43 |
Baseline characteristics
| Characteristic | Prior Brexpiprazole | Prior Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 11 | 46.1 years STANDARD_DEVIATION 11.5 | 45.8 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Ethnicity Ethnicity-Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 21 Participants | 24 Participants | 45 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 165 Participants | 169 Participants | 334 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 52 Participants | 47 Participants | 99 Participants |
| Race/Ethnicity, Customized Race Race-Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 129 Participants | 146 Participants | 275 Participants |
| Sex: Female, Male Female | 97 Participants | 92 Participants | 189 Participants |
| Sex: Female, Male Male | 91 Participants | 101 Participants | 192 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 184 | 0 / 184 |
| other Total, other adverse events | 13 / 184 | 26 / 184 |
| serious Total, serious adverse events | 11 / 184 | 8 / 184 |
Outcome results
Primary
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)
Population: Safety Sample included all participants who received at least 1 dose of IMP (brexpiprazole).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Prior Brexpiprazole | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Any grade | 79 Participants |
| Prior Brexpiprazole | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Mild | 60 Participants |
| Prior Brexpiprazole | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Moderate | 31 Participants |
| Prior Brexpiprazole | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Severe | 8 Participants |
| Prior Placebo | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Severe | 5 Participants |
| Prior Placebo | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Any grade | 86 Participants |
| Prior Placebo | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Moderate | 29 Participants |
| Prior Placebo | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity | TEAE, Mild | 68 Participants |