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

December 3, 2025 updated by: Axsome Therapeutics, Inc.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

456

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

  • Canada
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1Z9
        • Clinical Research Site
  • Puerto Rico
      • San Juan, Puerto Rico, 00918
        • Clinical Research Site
  • United States
    • Arizona
      • Peoria, Arizona, United States, 83581
        • Clinical Research Site
      • Tempe, Arizona, United States, 85282
        • Clinical Research Site
    • California
      • Long Beach, California, United States, 90807
        • Clinical Research Site
      • Santa Ana, California, United States, 92705
        • Clinical Research Site
      • Temecula, California, United States, 92591
        • Clinical Research Site
      • Walnut Creek, California, United States, 94596
        • Clinical Research Site
    • Florida
      • Bonita Springs, Florida, United States, 34134
        • Clinical Research Site
      • Brandon, Florida, United States, 33511
        • Clinical Research Site
      • Coral Springs, Florida, United States, 33067
        • 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
      • Lake City, Florida, United States, 32055
        • 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
      • Trinity, Florida, United States, 34655
        • Clinical Research Site
    • Georgia
      • Columbus, Georgia, United States, 31909
        • Clinical Research Site
    • Kansas
      • Wichita, Kansas, United States, 67214
        • 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
    • Missouri
      • Chesterfield, Missouri, United States, 63005
        • Clinical Research Site
    • New Jersey
      • 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
    • North Carolina
      • Charlotte, North Carolina, United States, 28211
        • Clinical Research Site
      • Hickory, North Carolina, United States, 28601
        • 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
      • Sugar Land, Texas, United States, 77478
        • 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:

  • 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.

Exclusion Criteria:

  • 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.

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 (dextromethorphan-bupropion)
  • Up to 52 weeks in the open-label segment;
  • Up to 24 weeks in the randomized double-blind segment (if applicable)
Drug: AXS-05 (dextromethorphan-bupropion)
AXS-05 tablets, taken twice daily
Placebo Comparator: Placebo
Up to 24 weeks in the randomized double-blind segment (if applicable)
Drug: Placebo
Placebo tablets, taken twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long-term Safety
Time Frame: up to 76 weeks
Incidence of treatment-emergent adverse events following dosing with AXS-05
up to 76 weeks
Time to relapse of agitation symptoms
Time Frame: up to 24 weeks
up to 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohen-Mansfield Agitation Inventory (CMAI)
Time Frame: up to 76 weeks
Change from Baseline to last dose in the CMAI
up to 76 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)

June 17, 2021

Primary Completion (Actual)

December 3, 2024

Study Completion (Actual)

December 21, 2024

Study Registration Dates

First Submitted

June 24, 2021

First Submitted That Met QC Criteria

June 24, 2021

First Posted (Actual)

July 1, 2021

Study Record Updates

Last Update Posted (Actual)

December 8, 2025

Last Update Submitted That Met QC Criteria

December 3, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AXS-05-AD-303

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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