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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04947553

Acronym

ACCORD-2

Enrollment

456

Registered

2021-07-01

Start date

2021-06-17

Completion date

2024-12-21

Last updated

2025-12-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Agitation in Patients With Dementia of the Alzheimer's Type, Agitation, Psychomotor, Alzheimer Disease

Keywords

AD agitation, AXS-05, NMDA receptor antagonist, dextromethorphan, bupropion, Axsome

Brief summary

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.

Interventions

DRUGAXS-05 (dextromethorphan-bupropion)

AXS-05 tablets, taken twice daily

DRUGPlacebo

Placebo tablets, taken twice daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

65 Years to 90 Years

Healthy volunteers

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.

Design outcomes

Primary

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

Other

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

Countries

Canada, Puerto Rico, United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026