AXS-05 for Alzheimer's Disease Agitation

No longer recruiting at 16 trial locations

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Axsome Therapeutics, Inc.

Disqualifiers: Hospitalized, Nursing home, Living alone, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 25 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the long-term safety of a new treatment called AXS-05 (also known as Auvelity or Dextromethorphan/bupropion) for individuals experiencing agitation due to Alzheimer's disease. The study focuses on those who have already participated in previous related trials. Participants should have a caregiver to assist with study requirements and medication. The trial aims to assess the safety of AXS-05 over an extended period. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you started a new medication since enrolling in the previous studies, it might be a concern if it poses a safety risk with AXS-05.

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

Research has shown that AXS-05, a treatment for restlessness in Alzheimer's patients, is generally well-tolerated. Previous studies found that it significantly reduces the likelihood of symptom recurrence in those with Alzheimer's-related restlessness. Importantly, AXS-05 has not been linked to cognitive impairment or excessive drowsiness, common issues with some other treatments. Overall, current research indicates that the safety of AXS-05 appears promising. ^{1 2 3 4 5}

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

AXS-05 is unique because it combines two active ingredients, dextromethorphan and bupropion, offering a new approach to treating agitation in Alzheimer's patients. Unlike standard treatments, which often rely on antipsychotics or sedatives, AXS-05 acts on the brain's neurotransmitter systems, potentially improving symptoms with fewer side effects. Researchers are excited about its novel mechanism of action and the possibility of providing a more effective and safer alternative for managing agitation in Alzheimer's disease.

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

Research has shown that AXS-05, the investigational treatment in this trial, may help reduce agitation in people with Alzheimer's. In earlier studies, AXS-05 significantly lowered the chance of agitation symptoms returning compared to a placebo (a pill with no active medicine). Specifically, only 7.5% of patients taking AXS-05 experienced a return of symptoms, a much lower rate than those taking the placebo. Additionally, symptoms took longer to return, suggesting it helps keep patients calm for a longer time. Overall, AXS-05 was well-tolerated, with patients experiencing few side effects. These findings suggest AXS-05 could be a helpful option for managing agitation in Alzheimer's disease. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals who have Alzheimer's disease with symptoms of agitation and participated in previous ADVANCE-2 or ACCORD-2 studies. It aims to understand the long-term safety of AXS-05, a medication intended to manage these symptoms.

Inclusion Criteria

Completed the treatment period in Study AXS-05-AD-304 or exited from Study AXS-05-AD-303 due to study completion

My caregiver agrees to follow the study's requirements and help me with my treatment.

Exclusion Criteria

I am currently living in a mental health facility, nursing home, or by myself.

Caregiver is unwilling or unable, in the opinion of the Investigator, to comply with study instructions

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AXS-05 for the treatment of Alzheimer's disease agitation

25 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AXS-05

Trial Overview The study tests the ongoing safety of AXS-05 (a combination of dextromethorphan and bupropion) in managing agitation associated with Alzheimer's over an extended period. This open-label trial allows all participants to receive the drug.

How Is the Trial Designed?

Group I: Open-Label Experimental Treatment 1 Intervention

Experimental: AXS-05 (dextromethorphan-bupropion) up to 25 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 (Auvelity) is an FDA-approved treatment for major depressive disorder that has shown significant efficacy in reducing depression scores in phase 3 trials, with effects noticeable within two weeks.

The treatment is well-tolerated, with mild-to-moderate side effects, and long-term studies indicate high remission rates of nearly 70% and response rates over 80%, making it a promising option for fast-acting depression relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder. McCarthy, B., Bunn, H., Santalucia, M., et al.[2023]

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]

Sublingual dexmedetomidine has a favorable efficacy profile for treating agitation in adults with schizophrenia or bipolar disorder, with a number needed to treat of 3 for significant response at 2 hours post-dose in both conditions.

The treatment's safety profile is also acceptable, as the number needed to harm for adverse events is generally greater than 10, except for somnolence, which has a number needed to harm of 7, indicating that the benefits outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: A Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Citrome, L., Risinger, R., Rajachandran, L., et al.[2023]

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]

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]

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. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/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 achieved ...

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 ... AXS-05 increased time-to-relapse vs placebo (hazard ratio = 0.275; P = .014). AXS-05 was associated with lower relapse rates vs placebo (7.5% vs ...

6. 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 ...

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 ...