Agitation in Patients With Dementia of the Alzheimer's TypePhase 2/3ADVANCENCT03226522

Addressing Dementia Via Agitation-Centered Evaluation

A Phase 2/3 study testing AXS-05 and Bupropion in people with Agitation in Patients With Dementia of the Alzheimer's Type and Alzheimer Disease, run by Axsome Therapeutics, Inc. at 78 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multi-center, randomized, double-blind, placebo-controlled study, to assess the efficacy and safety of AXS-05 in the treatment of agitation in patients with Alzheimer's disease. Read more about this study

Who is it for?: Ages 65 to 90 years
Conditions the study is for: Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation,Psychomotor
What is being tested?: AXS-05 and Bupropion
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 366 participants
Where: 78 sitesin 2 countries
Study dates: 13 Jul 2017to 17 Apr 2020
Phase: Phase 2/3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 65 to 90 years
All sexes
No healthy volunteers
Older adult

Who may be able to join

Diagnosis of probable Alzheimer's disease (AD) based on the 2011 National Institute on Aging-Alzheimer Association (NIA-AA) criteria.
Diagnosis of clinically signification agitation resulting from probable AD according to the International Psychogeriatric Association (IPA) provisional definition of agitation.

Who cannot join

Patient has dementia predominantly of non-Alzheimer's type.
Unable to comply with study procedures.
Medically inappropriate for study participation in the opinion of the investigator.

Trial locations and contacts

78 sites in 2 countries.

Country

City, postcode or hospital

78 sites in 2 countries

United States77 sites

Axsome Study Site
Albany, New York, 12208
Axsome Study Site
Apopka, Florida, 32703
Axsome study site
Atlanta, Georgia, 30331
Axsome study site
Avon, Indiana, 46123
Axsome study site
Baton Rouge, Louisiana, 70808
Axsome study site
Bellevue, Washington, 98007
Axsome study site
Boca Raton, Florida, 33487
Axsome study site
Boise, Idaho, 83704
Axsome study site
Boynton Beach, Florida, 33437
Axsome study site
Brooklyn, New York, 11229
Axsome study site
Canoga Park, California, 91303
Axsome Study Site
Charlotte, North Carolina, 28211
Axsome study site
Charlotte, North Carolina, 28270
Axsome Study Site
Charlottesville, Virginia, 22903
Axsome study site
Chesterfield, Missouri, 63005
Axsome study site
Cincinnati, Ohio, 45069
Axsome Study Site
Coconut Creek, Florida, 33066
Axsome Study Site
Colorado Springs, Colorado, 80910
Axsome study site
Costa Mesa, California, 92626
Axsome study site
Cromwell, Connecticut, 06416
Axsome Study Site
Dayton, Ohio, 45459
Axsome study site
Decatur, Georgia, 30030
Axsome study site
DeSoto, Texas, 75115
Axsome Study Site
Everett, Washington, 98201
Axsome Study Site
Flossmoor, Illinois, 60422
Axsome study site
Fresno, California, 93710
Axsome Study Site
Gilbert, Arizona, 85297
Axsome Study Site
Greenacres City, Florida, 33467
Axsome study site
Hallandale, Florida, 33009
Axsome Study Site
Hattiesburg, Mississippi, 39401
Axsome study site
Hialeah, Florida, 33012
Axsome Study Site
Honolulu, Hawaii, 96817
Axsome Study Site
Lake Charles, Louisiana, 70629
Axsome Study Site
Lake City, Florida, 32055
Axsome study site
Las Vegas, Nevada, 89102
Axsome Study Site
Las Vegas, Nevada, 89109
Axsome Study Site
Little Rock, Arkansas, 72209
Axsome study site
Long Beach, California, 90806
Axsome study site
Long Beach, California, 90807
Axsome Study Site
Los Alamitos, California, 90720
Axsome Study Site
McKinney, Texas, 75071
Axsome study site
Miami, Florida, 33122
Axsome study site
Miami, Florida, 33165
Axsome study site
New London, Connecticut, 06320
Axsome study site
New York, New York, 10036
Axsome study site
New York, New York, 10128
Axsome Study Site
Oklahoma City, Oklahoma, 73112
Axsome study site
Orem, Utah, 84058
Axsome Study Site
Orlando, Florida, 32807
Axsome Study Site
Overland Park, Kansas, 66212
Axsome study site
Pensacola, Florida, 32502
Axsome Study Site
Phoenix, Arizona, 85004
Axsome Study Site
Port Orange, Florida, 32127
Axsome Study Site
Princeton, New Jersey, 08540
Axsome Study Site
Richmond, Virginia, 23235
Axsome study site
Riverside, California, 92503
Axsome study site
Sacramento, California, 95821
Axsome study site
Santa Ana, California, 92705
Axsome Study Site
Santa Clarita, California, 91321
Axsome study site
Scottsdale, Arizona, 85251
Axsome study site
Scottsdale, Arizona, 85258
Axsome study site
Shaker Heights, Ohio, 44122
Axsome study site
Sherman Oaks, California, 91403
Axsome study site
Simi Valley, California, 93065
Axsome study site
Spokane, Washington, 99202
Axsome study site
Spring Hill, Florida, 34609
Axsome Study Site
St Louis, Missouri, 63128
Axsome study site
Staten Island, New York, 10312
Axsome study site
Tampa, Florida, 33609
Axsome study site
Tampa, Florida, 33613
Axsome study site
Temecula, California, 92591
Axsome study site
Toms River, New Jersey, 08755
Axsome Study Site
Topeka, Kansas, 66606
Axsome Study Site
Tucson, Arizona, 85704
Axsome study site
Ventura, California, 93003
Axsome study site
Wichita Falls, Texas, 76309
Axsome Study Site
Winston-Salem, North Carolina, 27103

Other trials in United States

Australia1 site

Axsome study site
Caulfield, Melbourne, Victoria, 3162

Other trials in Australia

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of AXS-05 for the Treatment of Agitation in Subjects With Dementia of the Alzheimer's Type

This is a multi-center, randomized, double-blind, placebo-controlled study, to assess the efficacy and safety of AXS-05 in the treatment of agitation in patients with Alzheimer's disease.

Conditions: Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation,Psychomotor
Being tested: AXS-05, Bupropion, Placebo
Medical subject headings: Alzheimer Disease, Psychomotor Agitation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AXS-05Drug
AXS-05
BupropionDrug
Bupropion
PlaceboDrug
Placebo

Study groups in NCT03226522
Study group	Role	What they receive
AXS-05	Experimental	AXS-05 tablets taken by mouth for 5 weeks. Receives: Drug: AXS-05
Bupropion	Active comparator	Bupropion tablets taken by mouth for 5 weeks. Receives: Drug: Bupropion
Placebo	Placebo comparator	Placebo tablets taken by mouth for 5 weeks. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in CMAI Total Score
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).
Measured: 5 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jul 201717 Apr 2020

First posted21 Jul 2017
Study start13 Jul 2017
Primary completion17 Apr 2020
Study completion17 Apr 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Agitation in Patients With Dementia of the Alzheimer's TypeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2/3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 366 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03226522
Sponsor's protocol ID: AXS-05-AD-301
Acronym: ADVANCE
Status last verified: Aug 2023
First submitted: 20 Jul 2017
Last updated: 13 Sep 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
A Study to Assess the Efficacy and Safety of ITI-1284 in the Treatment of Agitation Associated With Alzheimer's Dementia
Agitation Associated With Alzheimer's Dementia
RecruitingPhase 2
A Study of ONO-2020 in Patients With Agitation Associated With Alzheimer's Disease Dementia
Agitation Associated With Alzheimer's Disease Dementia
Not yet recruitingPhase 2/3
To Evaluate the Efficacy, Safety, and Tolerability of Dronabinol Oral Solution for Agitation in Patients With Alzheimer's Disease
Agitation in Dementia
RecruitingPhase 2
Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Alzheimer Disease, Dementia

All Agitation in Patients With Dementia of the Alzheimer's Type trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of AXS-05 for the Treatment of Agitation in Subjects With Dementia of the Alzheimer's Type
ClinicalTrials.gov ID: NCT03226522
Acronym / sponsor ID: ADVANCE / AXS-05-AD-301
Conditions: Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation,Psychomotor
Phase: Phase 2/3
Study type: Interventional
Recruitment status: Completed
Enrolment: 366 participants (actual)
Lead sponsor: Axsome Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 13 Jul 2017 (actual)
Primary completion: 17 Apr 2020 (actual)
Study completion: 17 Apr 2020 (actual)
First posted: 21 Jul 2017 (actual)
Results: Posted 13 Sep 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a multi-center, randomized, double-blind, placebo-controlled study, to assess the efficacy and safety of AXS-05 in the treatment of agitation in patients with Alzheimer's disease.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
AXS-05	Experimental	Drug: AXS-05AXS-05 tablets taken by mouth for 5 weeks.
Bupropion	Active comparator	Drug: BupropionBupropion tablets taken by mouth for 5 weeks.
Placebo	Placebo comparator	Drug: PlaceboPlacebo tablets taken by mouth for 5 weeks.

Who may qualify

Ages: 65 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Older adult

Key inclusion criteria (2 listed)

Diagnosis of probable Alzheimer's disease (AD) based on the 2011 National Institute on Aging-Alzheimer Association (NIA-AA) criteria.
Diagnosis of clinically signification agitation resulting from probable AD according to the International Psychogeriatric Association (IPA) provisional definition of agitation.

Key exclusion criteria (3 listed)

Patient has dementia predominantly of non-Alzheimer's type.
Unable to comply with study procedures.
Medically inappropriate for study participation in the opinion of the investigator.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AXS-05AXS-05	Drug	AXS-05
BupropionBupropion	Drug	Bupropion
PlaceboPlacebo	Drug	Placebo

Primary outcome

Change in CMAI Total Score
Time frame: 5 weeks
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).

Results and safety

Results posted to the registry on 13 Sep 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AXS-05	159	137
Bupropion	49	48
Placebo	158	136

Primary outcome: Change in CMAI Total Score

Time frame: 5 weeks. Mean (Standard Error). Unit: score on a scale

Measure	AXS-05 n = 152	Bupropion n = 49	Placebo n = 156
Value	-15.4 (1.25)	-10.0 (3.02)	-11.5 (1.10)

AXS-05 vs Placebo: p = 0.010, Mixed Models Analysis
AXS-05 vs Bupropion: p <0.001, Mixed Models Analysis

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

Adverse events

Time frame: Adverse events were collected from the Baseline visit through 30 days after the last study visit (up to 10 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AXS-05	5 of 159 (3.1%)	33 of 159 (20.8%)	0 of 159
Bupropion	4 of 49 (8.2%)	17 of 49 (34.7%)	1 of 49
Placebo	9 of 158 (5.7%)	24 of 158 (15.2%)	1 of 158

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Axsome Therapeutics WebsiteLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Agitation in Patients With Dementia of the Alzheimer's Type

RecruitingPhase 2
A Study to Assess the Efficacy and Safety of ITI-1284 in the Treatment of Agitation Associated With Alzheimer's Dementia
Agitation Associated With Alzheimer's Dementia
RecruitingPhase 2
A Study of ONO-2020 in Patients With Agitation Associated With Alzheimer's Disease Dementia
Agitation Associated With Alzheimer's Disease Dementia
Not yet recruitingPhase 2/3
To Evaluate the Efficacy, Safety, and Tolerability of Dronabinol Oral Solution for Agitation in Patients With Alzheimer's Disease
Agitation in Dementia
RecruitingPhase 2
Effects of THC-Free CBD Oil on Agitation in Patients With Alzheimer's Disease
Alzheimer Disease, Dementia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

78 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 78 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in CMAI Total Score (time frame: 5 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03226522.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.