AXS-05 for Alzheimer's Disease Agitation

(ADVANCE-2 Trial)

No longer recruiting at 56 trial locations

Overseen By Study Director

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Axsome Therapeutics, Inc.

Disqualifiers: Non-Alzheimer's dementia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well AXS-05 works for people with Alzheimer's disease who experience agitation. Agitation involves feeling restless, irritable, or upset, which can be challenging for both patients and caregivers. The study compares AXS-05 (a combination of dextromethorphan and bupropion) to a placebo (a pill with no active ingredients) to determine its effectiveness in reducing these symptoms. Suitable participants have been diagnosed with Alzheimer's disease and experience noticeable agitation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that AXS-05 is likely to be safe for humans?

Research has shown that AXS-05 is generally well-tolerated. One study found that AXS-05 did not impair thinking or cause drowsiness, common concerns with treatments for agitation in Alzheimer's disease. Another study examined the long-term safety of AXS-05 and found it safe for extended use in people with Alzheimer's. While some side effects occurred, they were not serious in these studies. Overall, these findings suggest that AXS-05 is safe for most people, but discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's disease agitation?

Researchers are excited about AXS-05 for Alzheimer's disease agitation because it offers a novel approach compared to current treatments like antipsychotics and benzodiazepines. AXS-05 is unique because it combines two active ingredients, dextromethorphan and bupropion, which work together to modulate neurotransmitters in the brain, potentially providing more effective relief from agitation. Unlike standard treatments that can take weeks to show results, AXS-05 has the potential to work faster, improving symptoms in just a few weeks. This dual mechanism not only targets the symptoms more precisely but also aims to reduce the side effects commonly seen with existing medications.

What evidence suggests that AXS-05 might be an effective treatment for Alzheimer's disease agitation?

Research has shown that AXS-05, which participants in this trial may receive, might help treat agitation in people with Alzheimer's. Studies found that AXS-05 significantly reduces the recurrence of agitation, resulting in fewer episodes for patients. It is also generally well-tolerated, with most patients experiencing no major side effects. Early clinical data suggest AXS-05 could be a promising option for managing symptoms of agitation linked to Alzheimer's disease. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with Alzheimer's disease who are experiencing significant agitation. Participants must be diagnosed based on specific criteria and able to follow the study procedures. Those with non-Alzheimer's dementia or deemed medically unfit by the investigator cannot join.

Inclusion Criteria

I have been diagnosed with significant agitation due to Alzheimer's disease.

Exclusion Criteria

You have a type of dementia that is not mainly caused by Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either AXS-05 or placebo for the treatment of agitation associated with Alzheimer's disease

5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AXS-05
• Placebo

Trial Overview The trial is testing AXS-05 against a placebo to see if it can safely reduce agitation in Alzheimer's patients. It involves multiple centers, where participants are randomly assigned to receive either the real drug or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: AXS-05 Experimental Treatment 1 Intervention

Up to 5 weeks

Group II: Placebo Placebo Group 1 Intervention

Up to 5 weeks

AXS-05 is already approved in United States for the following indications:

Approved in United States as Auvelity for:

• Major depressive disorder

Who Is Running the Clinical Trial?

Axsome Therapeutics, Inc.

Lead Sponsor

Trials

34

Recruited

11,600+

Published Research Related to This Trial

Dextromethorphan/bupropion, a fixed-dose combination medication, was approved in August 2022 for treating major depressive disorder (MDD) in adults, highlighting its efficacy as a new treatment option.

The combination works by utilizing dextromethorphan as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion enhances the bioavailability of dextromethorphan, potentially improving therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. Keam, SJ.[2022]

In a phase 3 trial involving 327 patients with major depressive disorder, AXS-05 (dextromethorphan-bupropion) significantly improved depressive symptoms compared to placebo, with effects noticeable as early as week 1.

The treatment led to a remission rate of 39.5% compared to 17.3% for placebo, and was generally well tolerated, with no serious side effects like weight gain or increased sexual dysfunction reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI). Iosifescu, DV., Jones, A., O'Gorman, C., et al.[2022]

Citalopram has shown promising efficacy in treating agitation in Alzheimer's disease dementia, potentially benefiting from a class effect seen in selective serotonin reuptake inhibitors, but concerns about its cardiac side effects have limited its use.

The article reviews safety and efficacy data for both citalopram and escitalopram, providing practical recommendations and risk mitigation strategies to enhance their use in clinical practice for managing agitation in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram. Aga, VM.[2022]

In a phase 2 trial involving 80 patients with major depressive disorder, dextromethorphan-bupropion (AXS-05) showed a significantly greater reduction in depression symptoms compared to bupropion, with a mean change in MADRS score of -13.7 points versus -8.8 points over 6 weeks.

Dextromethorphan-bupropion also resulted in higher remission rates (46.5% vs. 16.2% at week 6) and response rates (60.5% vs. 40.5% at week 6), while being generally well tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. Tabuteau, H., Jones, A., Anderson, A., et al.[2022]

Auvelity, a combination of dextromethorphan and bupropion, is approved for treating major depressive disorder in adults, but it carries a boxed warning for increased risk of suicidal thoughts and behaviors in younger patients.

Common side effects include dizziness, nausea, and headache, with a risk of seizures at higher doses, highlighting the importance of careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. Aschenbrenner, DS.[2023]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL-.0000000000205634

Efficacy and Safety Of AXS-05 in Agitation Associated with ... AXS-05 substantially reduced the risk of agitation symptom relapse in participants with AD and was generally well-tolerated in those who achieved sustained ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1064748124001878

Efficacy and Safety Of AXS-05 in Agitation Associated with ... ACCORD met its primary outcome as treatment with AXS-05 substantially reduced the risk of relapse and was generally well-tolerated for participants who ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35763451/

AXS-05: an investigational treatment for Alzheimer's ... Early released clinical trial data indicate that AXS-05 may be a useful option to treat agitation in patients with AD and that it appears to ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04947553

NCT04947553 | A Study to Assess the Long-term Safety ... This study will evaluate the long-term safety and efficacy of AXS-05 in subjects with Alzheimer's disease (AD) agitation. ... This study is a multi-center trial ...

5. alz-journals.onlinelibrary.wiley.com alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.086940

Clinical Profile of AXS‐05 in Treating Alzheimer's Disease ... ADVANCE-1 evaluated the acute effects of AXS-05 on improving ADA. Patients were randomized 1:1:1 for 5 weeks (AXS-05 or bupropion [105-mg] or ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1064748124001878

Efficacy and Safety Of AXS-05 in Agitation Associated with ... Efficacy and Safety Of AXS-05 in Agitation Associated with Alzheimer's Disease: Results From ACCORD, a Phase 3, Double-Blind, Placebo-Controlled, Relapse ...

7. axsome.com axsome.com/wp-content/uploads/2024/11/Axsome_AXS-05-Poster-Presentation_CTAD-2020.pdf

Results of the ADVANCE-1 Trial Safety Profile of AXS-05 in Alzheimer's Disease Agitation: Summary of Adverse Events. • AXS-05 was not associated with cognitive impairment or sedation. AXS-05.

8. healio.com healio.com/news/neurology/20250827/video-accord2-highlights-safety-efficacy-data-of-axs05-for-alzheimers-disease-agitation

VIDEO: ACCORD-2 highlights safety, efficacy data of AXS- ... Efficacy and safety of AXS-05 in Alzheimer's disease agitation: A phase 3 randomized withdrawal double-blind placebo-controlled study. Presented ...