Trial Outcomes & Findings for A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder (NCT NCT03257865)
NCT ID: NCT03257865
Last Updated: 2020-02-11
Results Overview
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).
COMPLETED
PHASE3
333 participants
Baseline, Week 3
2020-02-11
Participant Flow
The trial population consisted of adult participants (18 to 65 years) diagnosed with bipolar I disorder displaying an acute manic episode with or without mixed features requiring hospitalization. One participant randomized to brexpiprazole was not treated and excluded from the safety analysis set.
Participant milestones
| Measure |
Brexpiprazole
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Overall Study
STARTED
|
163
|
170
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
162
|
170
|
|
Overall Study
COMPLETED
|
128
|
135
|
|
Overall Study
NOT COMPLETED
|
35
|
35
|
Reasons for withdrawal
| Measure |
Brexpiprazole
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Overall Study
Adverse Event
|
4
|
8
|
|
Overall Study
Lack of Efficacy
|
1
|
2
|
|
Overall Study
Non-compliance with Study Drug
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
23
|
17
|
|
Overall Study
Physician Decision
|
3
|
1
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
4
|
Baseline Characteristics
A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes, Associated With Bipolar I Disorder
Baseline characteristics by cohort
| Measure |
Brexpiprazole
n=163 Participants
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
n=170 Participants
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
Total
n=333 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44.6 Years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
44.3 Years
STANDARD_DEVIATION 12.0 • n=7 Participants
|
44.5 Years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
85 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
167 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
78 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
166 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
90 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
192 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
70 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other Race
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
22 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
140 Participants
n=5 Participants
|
153 Participants
n=7 Participants
|
293 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other Ethnicity
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 3Population: Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.
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).
Outcome measures
| Measure |
Brexpiprazole
n=128 Participants
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
n=133 Participants
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Change From Baseline In Young-Mania Rating Scale (YMRS) Score At Week 3
|
-12.3 units on a scale
Standard Error 0.73
|
-10.7 units on a scale
Standard Error 0.71
|
SECONDARY outcome
Timeframe: Baseline, Week 3Population: Full Analysis Set: all participants who received at least 1 dose of study drug and had a baseline value and at least 1 valid post-randomization efficacy evaluation for YMRS Total Score in the double-blind treatment phase at the specified timepoint.
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.
Outcome measures
| Measure |
Brexpiprazole
n=128 Participants
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
n=133 Participants
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Change From Baseline In Clinical Global Impression-Bipolar (CGI-BP) Severity Score In Mania At Week 3
|
-1.31 units on a scale
Standard Deviation 1.22
|
-1.06 units on a scale
Standard Deviation 1.09
|
Adverse Events
Brexpiprazole
Placebo
Serious adverse events
| Measure |
Brexpiprazole
n=162 participants at risk
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
n=170 participants at risk
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Nervous system disorders
Epilepsy
|
0.00%
0/162 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
0.59%
1/170 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Psychiatric disorders
Mania
|
0.00%
0/162 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
1.2%
2/170 • Number of events 2 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
Other adverse events
| Measure |
Brexpiprazole
n=162 participants at risk
Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligram (mg)/day; titrated to a maximum of 4 mg/day.
|
Placebo
n=170 participants at risk
Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
3.7%
6/162 • Number of events 6 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
2.9%
5/170 • Number of events 5 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Gastrointestinal disorders
Nausea
|
1.2%
2/162 • Number of events 2 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
4.1%
7/170 • Number of events 8 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Nervous system disorders
Akathisia
|
8.0%
13/162 • Number of events 14 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
2.4%
4/170 • Number of events 4 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Nervous system disorders
Dizziness
|
3.1%
5/162 • Number of events 5 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
0.59%
1/170 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Nervous system disorders
Headache
|
6.2%
10/162 • Number of events 12 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
10.6%
18/170 • Number of events 19 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
|
Psychiatric disorders
Insomnia
|
3.1%
5/162 • Number of events 6 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
1.2%
2/170 • Number of events 2 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
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