Agitation in Patients With Dementia of the Alzheimer's TypePhase 3NCT06736509

An Open-Label Study to Assess the Long-term Safety of AXS-05 in Subjects With Dementia of the Alzheimer's Type, ADVANCE-2 and ACCORD-2 Extension Study

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 22 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

The primary objective of this open-label extension trial was to evaluate the long-term safety of AXS-05 for the treatment of Alzheimer's disease agitation in subjects that participated in ADVANCE-2 or ACCORD-2. 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?: No, everyone receives an active treatment
How many people: 139 participants
Where: 22 sitesin 2 countries
Study dates: 21 Nov 2024to 25 Apr 2025
Phase: Phase 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

Completed the treatment period in Study AXS-05-AD-304 or exited from Study AXS-05-AD-303 due to study completion.
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-304 and/or AXS-05-AD-303 which may pose a safety risk when taken concurrently with AXS-05.

Trial locations and contacts

22 sites in 2 countries.

Country

City, postcode or hospital

22 sites in 2 countries

United States21 sites

Clinical Research Site
Arlington, Virginia, 22205
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
Greenacres City, Florida, 33467
Clinical Research Site
Hialeah, Florida, 33012
Clinical Research Site
Mesquite, Texas, 75149
Clinical Research Site
Miami, Florida, 33126
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 Gardens, Florida, 33014
Clinical Research Site
Miami Lakes, Florida, 33014
Clinical Research Site
Pembroke Pines, Florida, 33025
Clinical Research Site
Peoria, Arizona, 85381
Clinical Research Site
Tampa, Florida, 33614
Clinical Research Site
Tampa, Florida, 33634
Clinical Research Site
Walnut Creek, California, 94596

Other trials in United States

Puerto Rico1 site

Clinical Research Site
San Juan, 00918

Other trials in Puerto Rico

About this study

Read the detailed description

This was a multi-center, open-label extension trial to evaluate the long-term safety of AXS-05 in subjects with Alzheimer's disease (AD) agitation that continued to receive AXS-05 given completion of ADVANCE-2 (AXS-05-AD-304) or ACCORD-2 (AXS-05-AD-303).

Conditions: Agitation in Patients With Dementia of the Alzheimer's Type, Alzheimer Disease, Agitation, Psychomotor
Being tested: AXS-05 (dextromethorphan-bupropion)
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

Study groups in NCT06736509
Study group	Role	What they receive
Open-Label	Experimental	Experimental: AXS-05 (dextromethorphan-bupropion) up to 25 weeks Receives: Drug: AXS-05 (dextromethorphan-bupropion)

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 25 weeks

Timeline

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

21 Nov 202425 Apr 2025

First posted16 Dec 2024
Study start21 Nov 2024
Primary completion17 Feb 2025
Study completion25 Apr 2025

Why it stopped: Study AXS-05-AD-305 was terminated due to completion of overall program objectives.

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.
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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 139 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06736509
Sponsor's protocol ID: AXS-05-AD-305
Status last verified: May 2026
First submitted: 12 Dec 2024
Last updated: 25 Jun 2026
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 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Study to Assess the Long-term Safety of AXS-05 in Subjects With Dementia of the Alzheimer's Type, ADVANCE-2 and ACCORD-2 Extension Study
ClinicalTrials.gov ID: NCT06736509
Acronym / sponsor ID: AXS-05-AD-305
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: TerminatedReason stopped: Study AXS-05-AD-305 was terminated due to completion of overall program objectives.
Enrolment: 139 participants (actual)
Lead sponsor: Axsome Therapeutics, Inc.Industry (pharma, biotech, devices)
Study start: 21 Nov 2024 (actual)
Primary completion: 17 Feb 2025 (actual)
Study completion: 25 Apr 2025 (actual)
First posted: 16 Dec 2024 (actual)
Results: Posted 25 Jun 2026

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Open-Label	Experimental	Drug: AXS-05 (dextromethorphan-bupropion)Experimental: AXS-05 (dextromethorphan-bupropion) up to 25 weeks

Who may qualify

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

Key inclusion criteria (2 listed)

Completed the treatment period in Study AXS-05-AD-304 or exited from Study AXS-05-AD-303 due to study completion.
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-304 and/or AXS-05-AD-303 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	Open-Label

Primary outcome

Long-Term Safety
Time frame: Up to 25 weeks
Incidence of treatment-emergent adverse events following dosing with AXS-05

Results and safety

Results posted to the registry on 25 Jun 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Open-Label	139	0

Primary outcome: Long-Term Safety

Time frame: Up to 25 weeks. Count of participants. Unit: Participants

Measure	Open-Label n = 139
Subjects with any TEAEs	16
Subjects with suspected to be drug-related TEAEs	7
Subjects with serious TEAEs	0
Subjects with TEAEs that led to drug withdrawal	0
Subjects with TEAEs that led to study discontinuation	0
Subjects with TEAEs that resulted in death	0
Subjects with no TEAEs	116

Adverse events

Time frame: Treatment emergent adverse events (TEAEs) were collected after administration of study drug through 7 days after the last dose (up to 25 weeks).. Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Open-Label	0 of 139 (0%)	16 of 139 (11.5%)	0 of 139

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
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.

22 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 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: stopped early, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, 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. 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?

Yes. Results are posted in the registry (first posted 25 Jun 2026). 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?

Long-Term Safety (time frame: Up to 25 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 NCT06736509.

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 25 Jun 2026.