Trial Outcomes & Findings for Addressing Dementia Via Agitation-Centered Evaluation (NCT NCT03226522)

Last Updated: 2023-09-13

Results Overview

The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item caregiver-rated questionnaire that assesses the frequency of agitation-related and disruptive behaviors in subjects with dementia. The scale contains 29 behaviors or items organized into four subscales: physically aggressive, physically non-aggressive, verbally aggressive, and verbally non-aggressive. The CMAI is administered by interviewing the caregiver and asking him or her to rate the frequency with which the subject manifests each behavior using a seven-point scale: 1=never (better outcome), 7=several times an hour (worse outcome). The CMAI total score is the sum of the scores for all of the items in the CMAI. CMAI total scores range from a minimum of 29 (better outcome) to a maximum of 203 (worse outcome).

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

366 participants

Primary outcome timeframe

5 weeks

Results posted on

2023-09-13

Participant Flow

Participant milestones

Participant milestones
Measure	AXS-05 AXS-05 tablets taken twice daily for 5 weeks. AXS-05: AXS-05	Bupropion Bupropion tablets taken twice daily for 5 weeks. Bupropion: Bupropion	Placebo Placebo tablets taken twice daily for 5 weeks. Placebo: Placebo
Overall Study STARTED	159	49	158
Overall Study Safety Population	159	49	158
Overall Study mITT Population	152	49	156
Overall Study COMPLETED	137	48	136
Overall Study NOT COMPLETED	22	1	22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Addressing Dementia Via Agitation-Centered Evaluation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AXS-05 n=159 Participants AXS-05 tablets taken by mouth for 5 weeks. AXS-05: AXS-05	Bupropion n=49 Participants Bupropion tablets taken by mouth for 5 weeks. Bupropion: Bupropion	Placebo n=158 Participants Placebo tablets taken by mouth for 5 weeks. Placebo: Placebo	Total n=366 Participants Total of all reporting groups
Age, Continuous	75.3 years STANDARD_DEVIATION 5.71 • n=5 Participants	76.4 years STANDARD_DEVIATION 6.13 • n=7 Participants	74.6 years STANDARD_DEVIATION 6.11 • n=5 Participants	75.1 years STANDARD_DEVIATION 5.95 • n=4 Participants
Sex: Female, Male Female	91 Participants n=5 Participants	22 Participants n=7 Participants	92 Participants n=5 Participants	205 Participants n=4 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	27 Participants n=7 Participants	66 Participants n=5 Participants	161 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black or African American	12 Participants n=5 Participants	5 Participants n=7 Participants	25 Participants n=5 Participants	42 Participants n=4 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	141 Participants n=5 Participants	43 Participants n=7 Participants	130 Participants n=5 Participants	314 Participants n=4 Participants

PRIMARY outcome

Timeframe: 5 weeks

Population: modified Intent-to-Treat (mITT) Population

Outcome measures

Outcome measures
Measure	AXS-05 n=152 Participants AXS-05 tablets taken twice daily for 5 weeks. AXS-05: AXS-05	Bupropion n=49 Participants Bupropion tablets taken twice daily for 5 weeks. Bupropion: Bupropion	Placebo n=156 Participants Placebo tablets taken twice daily for 5 weeks. Placebo: Placebo
Change in CMAI Total Score	-15.4 score on a scale Standard Error 1.25	-10.0 score on a scale Standard Error 3.02	-11.5 score on a scale Standard Error 1.10

Adverse Events

AXS-05

Serious events: 5 serious events

Other events: 33 other events

Deaths: 0 deaths

Bupropion

Serious events: 4 serious events

Other events: 17 other events

Deaths: 1 deaths

Placebo

Serious events: 9 serious events

Other events: 24 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	AXS-05 n=159 participants at risk AXS-05 tablets taken twice daily for 5 weeks. AXS-05: AXS-05	Bupropion n=49 participants at risk Bupropion tablets taken twice daily for 5 weeks. Bupropion: Bupropion	Placebo n=158 participants at risk Placebo tablets taken twice daily for 5 weeks. Placebo: Placebo
Gastrointestinal disorders Diarrhea	4.4% 7/159 • Number of events 9 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	6.1% 3/49 • Number of events 4 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	4.4% 7/158 • Number of events 7 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
General disorders Fatigue	1.9% 3/159 • Number of events 3 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	10.2% 5/49 • Number of events 5 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	1.3% 2/158 • Number of events 3 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Injury, poisoning and procedural complications Fall	2.5% 4/159 • Number of events 13 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	14.3% 7/49 • Number of events 11 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	1.9% 3/158 • Number of events 3 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Dizziness	6.3% 10/159 • Number of events 11 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	10.2% 5/49 • Number of events 5 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	3.2% 5/158 • Number of events 5 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Headache	3.8% 6/159 • Number of events 8 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	6.1% 3/49 • Number of events 3 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	2.5% 4/158 • Number of events 5 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Somnolence	8.2% 13/159 • Number of events 13 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	4.1% 2/49 • Number of events 2 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	3.2% 5/158 • Number of events 5 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Psychiatric disorders Insomnia	0.63% 1/159 • Number of events 2 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	6.1% 3/49 • Number of events 3 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	1.9% 3/158 • Number of events 4 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population

Additional Information

Study Director

Axsome Therapeutics

Phone: 212-332-5061

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	AXS-05 n=159 participants at risk AXS-05 tablets taken twice daily for 5 weeks. AXS-05: AXS-05	Bupropion n=49 participants at risk Bupropion tablets taken twice daily for 5 weeks. Bupropion: Bupropion	Placebo n=158 participants at risk Placebo tablets taken twice daily for 5 weeks. Placebo: Placebo
Gastrointestinal disorders Abdominal discomfort	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	2.0% 1/49 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Gastrointestinal disorders Abdominal pain	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	2.0% 1/49 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
General disorders Oedema peripheral	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Infections and infestations Staphylococcal infection	0.63% 1/159 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Infections and infestations Urinary tract infection	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	2.0% 1/49 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Injury, poisoning and procedural complications Fall	0.63% 1/159 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Metabolism and nutrition disorders Dehydration	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Metabolism and nutrition disorders Hyperglycaemia	0.63% 1/159 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.63% 1/159 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Dementia	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	2.0% 1/49 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/158 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Dementia Alzheimer's type	0.63% 1/159 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Syncope	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Nervous system disorders Transient ischaemic attack	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population
Psychiatric disorders Delirium	0.00% 0/159 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.00% 0/49 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population	0.63% 1/158 • Number of events 1 • Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks). Safety Population