Trial Outcomes & Findings for A Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Participants With Bipolar I Disorder. (NCT NCT03287869)
NCT ID: NCT03287869
Last Updated: 2020-08-17
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
381 participants
Primary outcome timeframe
From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Results posted on
2020-08-17
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
188
|
193
|
|
Overall Study
Analyzed For Safety (Safety Sample)
|
184
|
184
|
|
Overall Study
COMPLETED
|
105
|
100
|
|
Overall Study
NOT COMPLETED
|
83
|
93
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
14
|
12
|
|
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
Progressive Disease
|
1
|
0
|
|
Overall Study
Protocol Deviation
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
36
|
43
|
|
Overall Study
Early Closure of the Site
|
0
|
1
|
|
Overall Study
Physician Decision
|
5
|
5
|
|
Overall Study
Reason not Specified
|
6
|
3
|
Baseline Characteristics
A Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Participants With Bipolar I Disorder.
Baseline characteristics by cohort
| Measure |
Prior Brexpiprazole
n=188 Participants
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.
|
Prior Placebo
n=193 Participants
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.
|
Total
n=381 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.6 years
STANDARD_DEVIATION 11.0 • n=39 Participants
|
46.1 years
STANDARD_DEVIATION 11.5 • n=41 Participants
|
45.8 years
STANDARD_DEVIATION 11.2 • n=35 Participants
|
|
Sex: Female, Male
Female
|
97 Participants
n=39 Participants
|
92 Participants
n=41 Participants
|
189 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
91 Participants
n=39 Participants
|
101 Participants
n=41 Participants
|
192 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Race · White
|
129 Participants
n=39 Participants
|
146 Participants
n=41 Participants
|
275 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Race · Black or African American
|
52 Participants
n=39 Participants
|
47 Participants
n=41 Participants
|
99 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
|
3 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Race · Asian
|
2 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Race · Race-Other
|
2 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Hispanic or Latino
|
21 Participants
n=39 Participants
|
24 Participants
n=41 Participants
|
45 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Not Hispanic or Latino
|
165 Participants
n=39 Participants
|
169 Participants
n=41 Participants
|
334 Participants
n=35 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Ethnicity-Other
|
2 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
2 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: 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).
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.
Outcome measures
| Measure |
Prior Brexpiprazole
n=184 Participants
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.
|
Prior Placebo
n=184 Participants
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.
|
|---|---|---|
|
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
TEAE, Any grade
|
79 Participants
|
86 Participants
|
|
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
TEAE, Mild
|
60 Participants
|
68 Participants
|
|
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
TEAE, Moderate
|
31 Participants
|
29 Participants
|
|
Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity
TEAE, Severe
|
8 Participants
|
5 Participants
|
Adverse Events
Prior Brexpiprazole
Serious events: 11 serious events
Other events: 13 other events
Deaths: 0 deaths
Prior Placebo
Serious events: 8 serious events
Other events: 26 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Prior Brexpiprazole
n=184 participants at risk
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.
|
Prior Placebo
n=184 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Ear and labyrinth disorders
Vertigo Positional
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Gastrointestinal disorders
Upper Gastrointestinal Haemorrhage
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
General disorders
Chest Pain
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Infections and infestations
Cellulitis
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
Migraine
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
Bipolar Disorder
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
Depression
|
1.6%
3/184 • Number of events 3 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
1.1%
2/184 • Number of events 2 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
Mania
|
2.7%
5/184 • Number of events 5 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
Suicidal Behaviour
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/184 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
0.54%
1/184 • Number of events 1 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
Other adverse events
| Measure |
Prior Brexpiprazole
n=184 participants at risk
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.
|
Prior Placebo
n=184 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Akathisia
|
4.3%
8/184 • Number of events 9 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
9.2%
17/184 • Number of events 17 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
|
Nervous system disorders
Headache
|
2.7%
5/184 • Number of events 5 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
5.4%
10/184 • Number of events 12 • From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)
Safety Sample included all participants who received at least 1 dose of IMP.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
- Publication restrictions are in place
Restriction type: OTHER