Trial Outcomes & Findings for Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type (NCT NCT03620981)

NCT ID: NCT03620981

Last Updated: 2024-11-14

Results Overview

The CMAI assessed the frequency of agitated behaviors in elderly persons, such as hitting, cursing, and restlessness. It consisted of 29 items all rated on a 1 to 7 scale with 1 being the "best" rating and 7 being the "worst" rating. The minimum possible CMAI total score was 29, and the maximum possible CMAI total score was 203. A decrease in score indicated improvement in symptoms.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

410 participants

Primary outcome timeframe

Baseline and 10 weeks first dose, on average 10 weeks

Results posted on

2024-11-14

Participant Flow

Participant milestones

Participant milestones
Measure	Brexpiprazole 1 mg Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo Participants received placebo tablet once daily for 10 weeks.
Overall Study STARTED	112	149	149
Overall Study COMPLETED	83	102	116
Overall Study NOT COMPLETED	29	47	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Brexpiprazole 1 mg Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo Participants received placebo tablet once daily for 10 weeks.
Overall Study Adverse Event	14	38	25
Overall Study Lack of Efficacy	2	1	1
Overall Study Physician Decision	7	4	4
Overall Study Protocol Violation	1	2	1
Overall Study Withdrawal by Legal Representative	2	1	1
Overall Study Withdrawal by Care Giver	2	0	1
Overall Study Non-compliance with Study Drug	1	1	0

Baseline Characteristics

Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Brexpiprazole 1 mg n=112 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg n=149 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo n=149 Participants Participants received placebo tablet once daily for 10 weeks.	Total n=410 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Age, Categorical >=65 years	105 Participants n=5 Participants	145 Participants n=7 Participants	145 Participants n=5 Participants	395 Participants n=4 Participants
Age, Continuous	79.3 years STANDARD_DEVIATION 7.4 • n=5 Participants	80.2 years STANDARD_DEVIATION 6.4 • n=7 Participants	80.3 years STANDARD_DEVIATION 6.7 • n=5 Participants	80.0 years STANDARD_DEVIATION 6.8 • n=4 Participants
Sex: Female, Male Female	71 Participants n=5 Participants	105 Participants n=7 Participants	87 Participants n=5 Participants	263 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	44 Participants n=7 Participants	62 Participants n=5 Participants	147 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	112 Participants n=5 Participants	149 Participants n=7 Participants	149 Participants n=5 Participants	410 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Japan	112 participants n=5 Participants	149 participants n=7 Participants	149 participants n=5 Participants	410 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 10 weeks first dose, on average 10 weeks

Population: The full analysis set (FAS) comprised subjects who, after randomization, have received at least 1 dose of the IMP, and from whom CMAI total scores have been obtained at baseline and at least 1 time point after initiation of the treatment.

Outcome measures

Outcome measures
Measure	Brexpiprazole 1 mg n=108 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg n=148 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo n=147 Participants Participants received placebo tablet once daily for 10 weeks.
Change From Baseline in Cohen-Manfield Agitation Inventory(CMAI) Score at 10 Weeks After Dosing.	-11.7 units on a scale Standard Error 1.20	-15.2 units on a scale Standard Error 1.05	-8.0 units on a scale Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline and 10 weeks first dose, on average 10 weeks

Population: Efficacy sample（FAS）consisted of all participants who have received at least 1 dose of the IMP and have Baseline and at least one Post-Baseline efficacy evaluation.

The CGI-S was used to rate the severity of agitation. Scores were: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = among the most extremely ill participants. A decrease in score indicated improvement in symptoms.

Outcome measures

Outcome measures
Measure	Brexpiprazole 1 mg n=108 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg n=148 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo n=147 Participants Participants received placebo tablet once daily for 10 weeks.
Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 10 Weeks After Dosing.	-1.0 units on a scale Standard Error 0.1	-1.4 units on a scale Standard Error 0.09	-0.6 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline and 10 weeks first dose, on average 10 weeks

Population: Efficacy sample（FAS) consisted of all participants who have received at least 1 dose of the IMP and have Baseline and at least one Post-Baseline efficacy evaluation.

The CGI-I Scale was clinician-rated scale which assessed the total improvement of the patient's condition compared to that at baseline. Scores range from 0 to 7: 0 = Not assessed, 1= Very much improved, 2 = Much improved, 3= Minimally improved, 4= No change, 5= Minimally worse, 6= Much worse, 7= Very much worse. Higher scores indicate worse condition.

Outcome measures

Outcome measures
Measure	Brexpiprazole 1 mg n=108 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg n=148 Participants Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo n=147 Participants Participants received placebo tablet once daily for 10 weeks.
Clinical Global Impression of Improvement (CGI-I) Score at 10 Weeks After Dosing.	3.1 units on a scale Standard Deviation 1.3	2.6 units on a scale Standard Deviation 1.2	3.5 units on a scale Standard Deviation 1.4

Adverse Events

Brexpiprazole 1 mg

Serious events: 7 serious events

Other events: 77 other events

Deaths: 2 deaths

Brexpiprazole 2 mg

Serious events: 9 serious events

Other events: 113 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., Ltd.

Phone: 06-6943-7722

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Brexpiprazole 1 mg n=112 participants at risk Participants received a brexpiprazole 0.5 mg tablet once daily for 1 week followed by a 1 mg tablet once daily for 9 weeks.	Brexpiprazole 2 mg n=149 participants at risk Participants received a brexpiprazole 0.5 mg tablet once daily for the first week, followed by a 1 mg tablet once daily for the second week, and then, subsequently, a 2 mg tablet once daily for the following 8 weeks.	Placebo n=149 participants at risk Participants received placebo tablet once daily for 10 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
General disorders Cardiac death	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Hepatobiliary disorders Hepatic mass	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Infections and infestations Pneumonia	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Infections and infestations Pneumonia aspiration	1.8% 2/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	1.3% 2/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Injury, poisoning and procedural complications Femoral neck fracture	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders Akathisia	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders Cerebral infarction	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders Extrapyramidal disorder	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders IIIrd nerve paralysis	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders Seizure	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Psychiatric disorders Agitation	0.89% 1/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	1.3% 2/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.
Psychiatric disorders Psychiatric symptom	0.00% 0/112 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.00% 0/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.	0.67% 1/149 • Adverse events were monitored from signing of the informed consent form until follow-up for up to 35 days after the final day of IMP administration, on average 19 weeks The safety analysis comprised subjects who, after randomization, have received at least 1 dose of the IMP.