Trial Outcomes & Findings for Brexpiprazole for the Long-term Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type (NCT NCT03724942)

Last Updated: 2024-09-19

Results Overview

This trial enrolled subjects rolled over from Trial 331-102-00088, and the safety of brexpiprazole when administered for a maximum of 24 weeks (including the treatment period of Trial 331-102-00088) was evaluated.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

164 participants

Primary outcome timeframe

From baseline to week 14

Results posted on

2024-09-19

Participant Flow

Participant milestones

Participant milestones
Measure	ROLLOVER BREX Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO Rollover subjects from the placebo group in Trial 331-102-00088
Overall Study STARTED	102	62
Overall Study COMPLETED	73	44
Overall Study NOT COMPLETED	29	18

Reasons for withdrawal

Reasons for withdrawal
Measure	ROLLOVER BREX Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO Rollover subjects from the placebo group in Trial 331-102-00088
Overall Study Adverse Event	20	14
Overall Study Lack of Efficacy	0	1
Overall Study Physician Decision	5	2
Overall Study Protocol Violation	1	0
Overall Study Bedridden All Day and Required Full Assistance for Excretion, Meals and Change of Clothes	0	1
Overall Study Withdrawal by Legal Representative	3	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ROLLOVER BREX n=102 Participants Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=62 Participants Rollover subjects from the placebo group in Trial 331-102-00088	Total n=164 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
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	96 Participants n=5 Participants	60 Participants n=7 Participants	156 Participants n=5 Participants
Age, Continuous	79.0 years STANDARD_DEVIATION 6.8 • n=5 Participants	80.2 years STANDARD_DEVIATION 6.9 • n=7 Participants	79.5 years STANDARD_DEVIATION 6.8 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	36 Participants n=7 Participants	101 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	26 Participants n=7 Participants	63 Participants n=5 Participants
Race/Ethnicity, Customized Asian	102 Participants n=5 Participants	62 Participants n=7 Participants	164 Participants n=5 Participants
Region of Enrollment Japan	102 participants n=5 Participants	62 participants n=7 Participants	164 participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to week 14

Population: The safety analysis set comprised subjects who have received at least 1 dose of the IMP.

Outcome measures

Outcome measures
Measure	ROLLOVER BREX n=102 Participants Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=62 Participants Rollover subjects from the placebo group in Trial 331-102-00088
The Frequency of Subjects With Treatment-Emergent Adverse Events (TEAEs)	90.2 Percentage of percipitante	90.3 Percentage of percipitante

SECONDARY outcome

Timeframe: Baseline and 14 weeks after dosing

Population: The efficacy analysis set will comprise subjects who 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 treatment.

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.

Outcome measures

Outcome measures
Measure	ROLLOVER BREX n=96 Participants Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=60 Participants Rollover subjects from the placebo group in Trial 331-102-00088
Mean Change From Baseline in Cohen-Mansfield Agitation Inventory (CMAI) Score at 14 Weeks After Dosing	-2.5 Units on a scale Standard Deviation 9.9	-6.4 Units on a scale Standard Deviation 9.3

SECONDARY outcome

Timeframe: Baseline and 14 weeks after dosing.

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	ROLLOVER BREX n=96 Participants Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=60 Participants Rollover subjects from the placebo group in Trial 331-102-00088
Mean Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 14 Weeks After Dosing.	-0.2 Units on a scale Standard Deviation 0.8	-0.4 Units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: 14 weeks after dosing.

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	ROLLOVER BREX n=96 Participants Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=60 Participants Rollover subjects from the placebo group in Trial 331-102-00088
Clinical Global Impression of Improvement (CGI-I) Score at 14 Weeks After Dosing	3.1 Units on a scale Standard Deviation 1.2	2.7 Units on a scale Standard Deviation 1.1

Adverse Events

ROLLOVER BREX

Serious events: 7 serious events

Other events: 90 other events

Deaths: 0 deaths

ROLLOVER PLACEBO

Serious events: 4 serious events

Other events: 55 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	ROLLOVER BREX n=102 participants at risk Rollover subjects from the brexpiprazole group in Trial 331-102-00088	ROLLOVER PLACEBO n=62 participants at risk Rollover subjects from the placebo group in Trial 331-102-00088
General disorders Gait disturbance	2.0% 2/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Pneumonia	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	1.6% 1/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Infections and infestations Pneumonia aspiration	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	3.2% 2/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Injury, poisoning and procedural complications Femoral neck fracture	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Injury, poisoning and procedural complications Femur fracture	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	1.6% 1/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Injury, poisoning and procedural complications Subdural haematoma	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Investigations Blood creatine phosphokinase increased	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Musculoskeletal and connective tissue disorders Muscle rigidity	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Nervous system disorders Akathisia	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Nervous system disorders Bradykinesia	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Psychiatric disorders Agitation	0.98% 1/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	0.00% 0/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/102 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.	1.6% 1/62 • Adverse events were monitored from signing of the informed consent form through 35 days after last dose of study drug (Up to approximately Week 19) Subjects who received at least one dose of IMP were included in the safety analysis.

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., Ltd.

Phone: +81363617366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place