Agitation in Patients With Dementia of the Alzheimer's TypePhase 3ACCORD-2NCT04947553
A Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Alzheimer's Disease Agitation
A Phase 3 study testing AXS-05 (dextromethorphan-bupropion) in people with Agitation in Patients With Dementia of the Alzheimer's Type and Alzheimer Disease, run by Axsome Therapeutics, Inc. at 47 sites in 3 countries.
Trial summary
This study will evaluate the long-term safety and efficacy of AXS-05 in subjects with Alzheimer's disease (AD) agitation. 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 (dextromethorphan-bupropion)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 456 participants
- Where
- 47 sitesin 3 countries
- Study dates
- 17 Jun 2021to 21 Dec 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Participation in Study AXS-05-AD-302 or Study AXS-05-AD-304.
- Caregiver is willing to communicate with site personnel, comply with all required study procedures, and oversee administration and compliance with the subject's study treatment.
Who cannot join
- Caregiver is unwilling or unable, in the opinion of the investigator, to comply with study instructions.
- Subject is hospitalized in a mental health facility (e.g., psychiatric hospital or ward), living in a nursing home, or living alone.
- Any concurrent medical condition that might interfere with the conduct of the study, confound the interpretation of study results, or endanger the subject's well-being.
- Initiation of a new medication since enrolling in AXS-05-AD-302 or AXS-05-AD-304 which may pose a safety risk when taken concurrently with AXS-05.
Trial locations and contacts
47 sites in 3 countries.
47 sites in 3 countries
United States45 sites
Clinical Research Site
Arlington, Virginia, 22205
Clinical Research Site
Austin, Texas, 78737
Clinical Research Site
Bonita Springs, Florida, 34134
Clinical Research Site
Braintree, Massachusetts, 02184
Clinical Research Site
Brandon, Florida, 33511
Clinical Research Site
Brooklyn, New York, 11229
Clinical Research Site
Charlotte, North Carolina, 28211
Clinical Research Site
Chesterfield, Missouri, 63005
Clinical Research Site
Columbus, Georgia, 31909
Clinical Research Site
Coral Springs, Florida, 33067
Clinical Research Site
Cypress, Texas, 77429
Clinical Research Site
Flint, Michigan, 48532
Clinical Research Site
Greenacres City, Florida, 33467
Clinical Research Site
Hialeah, Florida, 33012
Clinical Research Site
Hickory, North Carolina, 28601
Clinical Research Site
Hollywood, Florida, 33024
Clinical Research Site
Kissimmee, Florida, 34741
Clinical Research Site
Lake City, Florida, 32055
Clinical Research Site
Long Beach, California, 90807
Clinical Research Site
Mesquite, Texas, 75149
Clinical Research Site
Miami, Florida, 33126
Clinical Research Site
Miami, Florida, 33135
Clinical Research Site
Miami, Florida, 33145
Clinical Research Site
Miami, Florida, 33155
Clinical Research Site
Miami, Florida, 33165
Clinical Research Site
Miami, Florida, 33173
Clinical Research Site
Miami, Florida, 33175
Clinical Research Site
Miami Gardens, Florida, 33014
Clinical Research Site
Miami Lakes, Florida, 33014
Clinical Research Site
New Windsor, New York, 12553
Clinical Research Site
Orlando, Florida, 32807
Clinical Research Site
Pembroke Pines, Florida, 33025
Clinical Research Site
Peoria, Arizona, 83581
Clinical Research Site
Rochester Hills, Michigan, 48307
Clinical Research Site
Santa Ana, California, 92705
Clinical Research Site
Staten Island, New York, 10314
Clinical Research Site
Sugar Land, Texas, 77478
Clinical Research Site
Tampa, Florida, 33614
Clinical Research Site
Tampa, Florida, 33634
Clinical Research Site
Temecula, California, 92591
Clinical Research Site
Tempe, Arizona, 85282
Clinical Research Site
Toms River, New Jersey, 08755
Clinical Research Site
Trinity, Florida, 34655
Clinical Research Site
Walnut Creek, California, 94596
Clinical Research Site
Wichita, Kansas, 67214
About this study
Official title: An Open-Label and Double-Blind, Randomized Withdrawal Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Dementia of the Alzheimer's Type
This study will evaluate the long-term safety and efficacy of AXS-05 in subjects with Alzheimer's disease (AD) agitation.
Read the detailed description
This study is a multi-center trial consisting of an open-label segment of up to 52 weeks, followed by a double-blind, placebo-controlled, randomized withdrawal segment. Subjects participating in the randomized-withdrawal segment will be randomized in a 1:1 ratio either to continue to receive AXS-05 or switch to placebo, for up to 24 weeks.
- Conditions
- Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation, Psychomotor
- Being tested
- AXS-05 (dextromethorphan-bupropion), Placebo
- Keywords
- AD agitation, AXS-05, NMDA receptor antagonist, dextromethorphan, bupropion, Axsome
- 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-05 (dextromethorphan-bupropion)Drug
AXS-05 tablets, taken twice daily
PlaceboDrug
Placebo tablets, taken twice daily
| Study group | Role | What they receive |
|---|---|---|
| AXS-05 (dextromethorphan-bupropion) | Experimental | * Up to 52 weeks in the open-label segment;
* Up to 24 weeks in the randomized double-blind segment (if applicable) Receives: Drug: AXS-05 (dextromethorphan-bupropion) |
| Placebo | Placebo comparator | Up to 24 weeks in the randomized double-blind segment (if applicable) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term Safety
Incidence of treatment-emergent adverse events following dosing with AXS-05
Measured: up to 76 weeks
Time to relapse of agitation symptoms
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start17 Jun 2021
- Primary completion3 Dec 2024
- Study completion21 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Agitation in Patients With Dementia of the Alzheimer's TypeStudies of the same condition, open and under way.
- More trials run by Axsome Therapeutics, Inc.The sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 456 participants (actual)
Sponsor and investigators
- Lead sponsor
- Axsome Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04947553
- Sponsor's protocol ID
- AXS-05-AD-303
- Acronym
- ACCORD-2
- Status last verified
- Dec 2025
- First submitted
- 24 Jun 2021
- Last updated
- 8 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label and Double-Blind, Randomized Withdrawal Study to Assess the Long-term Safety and Efficacy of AXS-05 in Subjects With Dementia of the Alzheimer's Type
- ClinicalTrials.gov ID
- NCT04947553
- Acronym / sponsor ID
- ACCORD-2 / AXS-05-AD-303
- Conditions
- Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation, Psychomotor
- Keywords
- AD agitation, AXS-05, NMDA receptor antagonist, dextromethorphan, bupropion, Axsome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 456 participants (actual)
- Lead sponsor
- Axsome Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jun 2021 (actual)
- Primary completion
- 3 Dec 2024 (actual)
- Study completion
- 21 Dec 2024 (actual)
- First posted
- 1 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the long-term safety and efficacy of AXS-05 in subjects with Alzheimer's disease (AD) agitation.
Detailed description
This study is a multi-center trial consisting of an open-label segment of up to 52 weeks, followed by a double-blind, placebo-controlled, randomized withdrawal segment. Subjects participating in the randomized-withdrawal segment will be randomized in a 1:1 ratio either to continue to receive AXS-05 or switch to placebo, for up to 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AXS-05 (dextromethorphan-bupropion) | Experimental | Drug: AXS-05 (dextromethorphan-bupropion)* Up to 52 weeks in the open-label segment; * Up to 24 weeks in the randomized double-blind segment (if applicable) |
| Placebo | Placebo comparator | Drug: PlaceboUp to 24 weeks in the randomized double-blind segment (if applicable) |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- Participation in Study AXS-05-AD-302 or Study AXS-05-AD-304.
- Caregiver is willing to communicate with site personnel, comply with all required study procedures, and oversee administration and compliance with the subject's study treatment.
Key exclusion criteria (4 listed)
- Caregiver is unwilling or unable, in the opinion of the investigator, to comply with study instructions.
- Subject is hospitalized in a mental health facility (e.g., psychiatric hospital or ward), living in a nursing home, or living alone.
- Any concurrent medical condition that might interfere with the conduct of the study, confound the interpretation of study results, or endanger the subject's well-being.
- Initiation of a new medication since enrolling in AXS-05-AD-302 or AXS-05-AD-304 which may pose a safety risk when taken concurrently with AXS-05.
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-05 (dextromethorphan-bupropion)AXS-05 tablets, taken twice daily | Drug | AXS-05 (dextromethorphan-bupropion) |
| PlaceboPlacebo tablets, taken twice daily | Drug | Placebo |
Primary outcome
Long-term Safety
Time frame: up to 76 weeks
Incidence of treatment-emergent adverse events following dosing with AXS-05
Time to relapse of agitation symptoms
Time frame: up to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2025.
- Axsome Therapeutics WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
47 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AXS-05 (dextromethorphan-bupropion) in people with Agitation in Patients With Dementia of the Alzheimer's Type and Alzheimer Disease, run by Axsome Therapeutics, Inc. at 47 sites in 3 countries.
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 4 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 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in United States, Canada, Puerto Rico. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Long-term Safety (time frame: up to 76 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Dec 2025.