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

November 20, 2025 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 is 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

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

408

Phase

  • 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 Locations

  • Puerto Rico
      • Bayamón, Puerto Rico, 00961
        • Clinical Research Site
      • San Juan, 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
      • Greenacres City, 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, 10312
        • 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
      • Sugar Land, 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

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
Intervention / Treatment
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

Outcome Measure
Time Frame
Cohen-Mansfield Agitation Inventory (CMAI)
Time Frame: Up to 5 weeks
Up to 5 weeks

Collaborators and Investigators

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

Sponsor

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)

September 6, 2022

Primary Completion (Actual)

November 21, 2024

Study Completion (Actual)

December 21, 2024

Study Registration Dates

First Submitted

September 23, 2022

First Submitted That Met QC Criteria

September 23, 2022

First Posted (Actual)

September 28, 2022

Study Record Updates

Last Update Posted (Actual)

November 26, 2025

Last Update Submitted That Met QC Criteria

November 20, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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