AXS-05 for Alzheimer's Disease Agitation

(ADVANCE-2 Trial)

Recruiting at 55 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

408 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new medication called AXS-05 to see if it can help reduce agitation in people with Alzheimer's disease. The goal is to find out if AXS-05 can balance brain chemicals to calm agitation and improve behavior. AXS-05, a combination of dextromethorphan and bupropion, is being investigated for its potential to treat agitation in Alzheimer's disease and has shown promise in early clinical trials.

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.

What data supports the effectiveness of the drug AXS-05 for Alzheimer's Disease Agitation?

AXS-05, a combination of dextromethorphan and bupropion, has been approved for treating major depressive disorder, suggesting its potential effectiveness in altering brain chemistry related to mood and behavior, which may also help with agitation in Alzheimer's disease. ^{1 2 3 4 5}

Is AXS-05 (Dextromethorphan-Bupropion) safe for humans?

AXS-05, also known as Auvelity, has been approved for treating major depressive disorder in adults. It carries a warning about the risk of suicidal thoughts in young people and can cause side effects like dizziness, nausea, and headaches. Seizures are possible, especially at higher doses. ^{1 3 5 6 7}

What makes the drug AXS-05 unique for treating agitation in Alzheimer's disease?

AXS-05 is unique because it combines dextromethorphan, which affects brain receptors involved in mood and behavior, with bupropion, which helps increase the effectiveness of dextromethorphan. This combination is taken orally and is already approved for treating major depressive disorder, making it a novel approach for Alzheimer's-related agitation. ^{1 2 3 4 6}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dextromethorphan/Bupropion: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial. [2018]

3. United States 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). [2022]

4. England pubmed.ncbi.nlm.nih.gov

R- and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

New Combination Drug for Depression. [2023]