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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05557409

Acronym

ADVANCE-2

Enrollment

408

Registered

2022-09-28

Start date

2022-09-06

Completion date

2024-12-21

Last updated

2026-08-13

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

Conditions

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

Keywords

AD agitation, AXS-05, NMDA receptor antagonist, dextromethorphan, bupropion, Axsome, ADVANCE-2

Brief summary

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.

Detailed description

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

Interventions

DRUGAXS-05

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

* 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.

Design outcomes

Primary

Measure	Time frame	Description
Cohen-Mansfield Agitation Inventory (CMAI)	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).

Countries

Puerto Rico, United States

Baseline characteristics

Characteristic	—
Age, Continuous	74.3 years STANDARD_DEVIATION 5.58
Race/Ethnicity, Customized Asian	2 participants
Race/Ethnicity, Customized Black or African American	41 participants
Race/Ethnicity, Customized Other	1 participants
Race/Ethnicity, Customized White	362 participants
Sex: Female, Male Female	130 Participants
Sex: Female, Male Male	74 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 204	0 / 204
other Total, other adverse events	27 / 204	15 / 204
serious Total, serious adverse events	2 / 204	0 / 204

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 14, 2026