A Study to Assess the Efficacy and Safety of AXS-05 in Subjects With Alzheimer's Disease Agitation (ADVANCE-2)

July 22, 2026 updated by: Axsome Therapeutics, Inc.

ADVANCE-2: Addressing Dementia Via Agitation-Centered Evaluation 2: A Randomized, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of AXS-05 for the Treatment of Alzheimer's Disease Agitation

This trial was a multi-center, double-blind, placebo-controlled, randomized study to evaluate the efficacy and safety of AXS-05 compared to placebo for the treatment of agitation associated with Alzheimer's disease.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Eligible subjects were randomized in a 1:1 ratio for up to 5 weeks to be treated with AXS-05 or placebo.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
408

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Puerto Rico
    • Puerto Rico
      • Bayamón, Puerto Rico, Puerto Rico, 00961
        • Clinical Research Site
      • San Juan, Puerto Rico, Puerto Rico, 00918
        • Clinical Research Site
  • United States
    • Arizona
      • Peoria, Arizona, United States, 85381
        • Clinical Research Site
      • Tempe, Arizona, United States, 85282
        • Clinical Research Site
      • Tucson, Arizona, United States, 85710
        • Clinical Research Site
    • California
      • Canoga Park, California, United States, 91303
        • Clinical Research Site
      • Long Beach, California, United States, 90807
        • Clinical Research Site
      • Los Alamitos, California, United States, 90720
        • Clinical Research Site
      • Walnut Creek, California, United States, 94596
        • Clinical Research Site
      • West Covina, California, United States, 91790
        • Clinical Research Site
    • Florida
      • Bonita Springs, Florida, United States, 34134
        • Clinical Research Site
      • Brandon, Florida, United States, 33511
        • Clinical Research Site
      • Green Acres, Florida, United States, 33467
        • Clinical Research Site
      • Hialeah, Florida, United States, 33012
        • Clinical Research Site
      • Hollywood, Florida, United States, 33024
        • Clinical Research Site
      • Kissimmee, Florida, United States, 34741
        • Clinical Research Site
      • Miami, Florida, United States, 33155
        • Clinical Research Site
      • Miami, Florida, United States, 33175
        • Clinical Research Site
      • Miami, Florida, United States, 33126
        • Clinical Research Site
      • Miami, Florida, United States, 33145
        • Clinical Research Site
      • Miami, Florida, United States, 33165
        • Clinical Research Site
      • Miami, Florida, United States, 33135
        • Clinical Research Site
      • Miami, Florida, United States, 33173
        • Clinical Research Site
      • Miami Gardens, Florida, United States, 33014
        • Clinical Research Site
      • Miami Lakes, Florida, United States, 33014
        • Clinical Research Site
      • Orlando, Florida, United States, 32807
        • Clinical Research Site
      • Pembroke Pines, Florida, United States, 33025
        • Clinical Research Site
      • Tampa, Florida, United States, 33634
        • Clinical Research Site
      • Tampa, Florida, United States, 33614
        • Clinical Research Site
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Clinical Research Site
      • College Park, Georgia, United States, 30349
        • Clinical Research Site
      • Columbus, Georgia, United States, 31909
        • Clinical Research Site
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Clinical Research Site
    • Louisiana
      • Marrero, Louisiana, United States, 70072
        • Clinical Research Site
    • Massachusetts
      • Braintree, Massachusetts, United States, 02184
        • Clinical Research Site
    • Michigan
      • Flint, Michigan, United States, 48532
        • Clinical Research Site
      • Rochester Hills, Michigan, United States, 48307
        • Clinical Research Site
      • Troy, Michigan, United States, 48085
        • Clinical Research Site
    • Missouri
      • Chesterfield, Missouri, United States, 63005
        • Clinical Research Site
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Clinical Research Site
      • Toms River, New Jersey, United States, 08755
        • Clinical Research Site
    • New York
      • Brooklyn, New York, United States, 11229
        • Clinical Research Site
      • New Windsor, New York, United States, 12553
        • Clinical Research Site
      • Staten Island, New York, United States, 10314
        • Clinical Research Site
      • Woodmere, New York, United States, 11598
        • Clinical Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
        • Clinical Research Site
      • Hickory, North Carolina, United States, 28601
        • Clinical Research Site
    • Ohio
      • Middleburg Heights, Ohio, United States, 44130
        • Clinical Research Site
    • Texas
      • Austin, Texas, United States, 78737
        • Clinical Research Site
      • Cypress, Texas, United States, 77429
        • Clinical Research Site
      • Mesquite, Texas, United States, 75149
        • Clinical Research Site
      • San Antonio, Texas, United States, 78229
        • Clinical Research Site
      • Sugarland, Texas, United States, 77478
        • Clinical Research Site
    • Vermont
      • Rutland, Vermont, United States, 05701
        • Clinical Research Site
    • Virginia
      • Arlington, Virginia, United States, 22205
        • Clinical Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 90 years (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AXS-05
Up to 5 weeks
Drug: AXS-05
AXS-05 tablets, taken twice daily
Placebo Comparator: Placebo
Up to 5 weeks
Drug: Placebo
Placebo tablets, taken twice daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cohen-Mansfield Agitation Inventory (CMAI)
Time Frame: Up to 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).
Up to 5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Axsome Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 6, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 21, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 21, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 23, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 23, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AXS-05-AD-304

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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