Trial Outcomes & Findings for A Trial to Assess Brexpiprazole Versus Placebo for the Treatment of Acute Manic Episodes Associated With Bipolar I Disorder (NCT NCT03259555)

Last Updated: 2020-02-10

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 (MMRM).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

322 participants

Primary outcome timeframe

Baseline, Week 3

Results posted on

2020-02-10

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.

Participant milestones

Participant milestones
Measure	Brexpiprazole Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (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	158	164
Overall Study Received At Least 1 Dose of Study Drug	158	163
Overall Study COMPLETED	124	134
Overall Study NOT COMPLETED	34	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Brexpiprazole Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (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	6	4
Overall Study Lack of Efficacy	6	4
Overall Study Lost to Follow-up	0	2
Overall Study Non-Compliance With Study Drug	1	0
Overall Study Progressive Disease	0	2
Overall Study Withdrawal by Subject	19	16
Overall Study Physician Decision	1	2
Overall Study Other	1	0

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

Baseline characteristics by cohort
Measure	Brexpiprazole n=158 Participants Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.	Placebo n=164 Participants Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.	Total n=322 Participants Total of all reporting groups
Age, Continuous	43.4 Years STANDARD_DEVIATION 11.7 • n=5 Participants	44.5 Years STANDARD_DEVIATION 11.2 • n=7 Participants	44.0 Years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	80 Participants n=5 Participants	83 Participants n=7 Participants	163 Participants n=5 Participants
Sex: Female, Male Male	78 Participants n=5 Participants	81 Participants n=7 Participants	159 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	141 Participants n=5 Participants	141 Participants n=7 Participants	282 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity - Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	95 Participants n=5 Participants	113 Participants n=7 Participants	208 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	54 Participants n=5 Participants	51 Participants n=7 Participants	105 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race - Other	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 3

Population: 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.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=124 Participants Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.	Placebo n=134 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	-10.6 units on a scale Standard Error 0.72	-10.8 units on a scale Standard Error 0.70

SECONDARY outcome

Timeframe: Baseline, 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.

Outcome measures

Outcome measures
Measure	Brexpiprazole n=124 Participants Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.	Placebo n=134 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	-1.12 units on a scale Standard Deviation 1.06	-1.21 units on a scale Standard Deviation 1.13

Adverse Events

Brexpiprazole

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Brexpiprazole n=158 participants at risk Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.	Placebo n=163 participants at risk Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
Blood and lymphatic system disorders Thrombocytopenia	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	0.00% 0/163 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Infections and infestations Varicella	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	0.00% 0/163 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Nervous system disorders Akathisia	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	0.00% 0/163 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Nervous system disorders Dystonia	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	0.00% 0/163 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Psychiatric disorders Mania	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	0.61% 1/163 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).

Other adverse events

Other adverse events
Measure	Brexpiprazole n=158 participants at risk Brexpiprazole was administered orally with flexible dosing from 2 to 4 milligrams (mg)/day; titrated to a maximum of 4 mg/day.	Placebo n=163 participants at risk Matching placebo was administered orally in the same way as brexpiprazole to maintain the blind.
Nervous system disorders Akathisia	5.1% 8/158 • Number of events 8 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	1.2% 2/163 • Number of events 2 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Nervous system disorders Headache	3.8% 6/158 • Number of events 8 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	6.7% 11/163 • Number of events 11 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Gastrointestinal disorders Constipation	1.3% 2/158 • Number of events 2 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	3.7% 6/163 • Number of events 6 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Gastrointestinal disorders Nausea	2.5% 4/158 • Number of events 4 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	3.1% 5/163 • Number of events 6 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).
Psychiatric disorders Agitation	0.63% 1/158 • Number of events 1 • From Day 1 (after dosing) through 6 weeks (3 weeks treatment, 3 weeks safety follow-up).	3.1% 5/163 • Number of events 5 • 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.

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.
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