KarXT for Psychosis in Alzheimer's Disease

(ADEPT-4 Trial)

Recruiting at 531 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Disqualifiers: Schizophrenia, Bipolar, Major depression, 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: 12 weeks

406 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of a drug called KarXT for treating psychosis (seeing or hearing things that are not there) in people with Alzheimer's Disease. Participants will receive either KarXT or a placebo (a pill with no active medicine) to compare results. The trial seeks adults diagnosed with Alzheimer's who have experienced psychotic symptoms for at least two months. These symptoms must not be caused by other conditions like schizophrenia. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that KarXT is likely to be safe for humans?

Research has shown that KarXT is generally well-tolerated. In earlier studies, reported side effects aligned with KarXT's effects on specific brain areas. While some side effects were observed, they were anticipated based on the drug's mechanism. Importantly, these side effects, such as changes in appetite or sleep, did not differ significantly from those of other similar treatments. This suggests that KarXT is relatively safe for use. However, discussing any concerns with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

KarXT is unique because it combines two components, xanomeline and trospium, to target symptoms of psychosis in Alzheimer's disease. Most treatments for this condition rely on antipsychotics, which can have significant side effects and limited effectiveness. KarXT works differently by selectively targeting muscarinic receptors in the brain, potentially offering a more targeted approach with fewer side effects. Researchers are excited about KarXT because it promises to address psychosis symptoms more effectively and safely compared to current standard treatments.

What evidence suggests that KarXT might be an effective treatment for psychosis in Alzheimer's Disease?

Research has shown that KarXT, a combination of xanomeline and trospium, may help treat symptoms of psychosis. Participants in this trial may receive KarXT, which studies have found to reduce psychosis in individuals with Alzheimer's Disease and schizophrenia. One study showed improvement in psychosis symptoms after just five weeks of treatment. The treatment likely works by affecting specific brain areas involved in psychosis. Although these results are promising, further research aims to better understand its benefits for Alzheimer's-related psychosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with mild to severe Alzheimer's Disease who also have moderate to severe psychosis related to their condition. Specific eligibility details are not provided, but typically participants must meet certain health criteria and not be on conflicting medications.

Inclusion Criteria

I am between 55 and 90 years old.

I have been diagnosed with Alzheimer's disease.

Patient must have a history of psychotic symptoms (meeting International Psychogeriatric Association criteria) for at least 2 months prior to Screening (Visit 1) (participants may or may not have symptoms of agitation)

Exclusion Criteria

Patients are not able to participate if they have certain safety concerns, including certain laboratory test irregularities

I have not had a major depressive episode with psychosis or been diagnosed with bipolar, schizophrenia, or schizoaffective disorder in the last year.

My dementia is not due to schizophrenia or similar conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either KarXT or placebo to evaluate safety and efficacy for psychosis associated with Alzheimer's Disease

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT

Trial Overview The study is testing KarXT against a placebo to see if it's safe and effective in treating psychosis symptoms in Alzheimer's patients. Participants will randomly receive either the actual medication or a placebo for comparison.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Group II: KarXT Experimental Treatment 1 Intervention

KarXT is already approved in United States for the following indications:

Approved in United States as Cobenfy for:

• Schizophrenia

Who Is Running the Clinical Trial?

Karuna Therapeutics

Lead Sponsor

Trials

17

Recruited

4,100+

Published Research Related to This Trial

In a pilot study involving 9 outpatients with probable Alzheimer's disease, haloperidol (1 to 5 mg daily) showed improvement in psychosis and behavioral disturbances, as confirmed by double-blind ratings.

However, patients experienced significant extrapyramidal side effects and a decline in cognitive function, indicating that while haloperidol may help with certain symptoms, its overall safety and efficacy in this population are compromised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer's disease. Devanand, DP., Sackeim, HA., Brown, RP., et al.[2019]

Vitamin D usage was more common among Alzheimer's disease patients without psychosis symptoms, and it was linked to a delay in the onset of psychosis, suggesting a potential preventive role.

The study identified that vitamin D affects genes related to calcium signaling, which may help in developing new treatments for psychosis in Alzheimer's patients, and genetic variations in these genes could help identify patients who might benefit from vitamin D therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients. Wang, L., Ying, J., Fan, P., et al.[2020]

In a 10-week study involving 256 institutionalized Alzheimer's patients, aripiprazole did not show significant improvement in primary psychotic symptoms compared to placebo, indicating it may not be effective for this specific use.

However, aripiprazole did lead to improvements in secondary symptoms like agitation, anxiety, and depression, with a low incidence of adverse effects, particularly mild somnolence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled study of aripiprazole for the treatment of psychosis in nursing home patients with Alzheimer disease. Streim, JE., Porsteinsson, AP., Breder, CD., et al.[2022]

Approximately 50% of individuals with Alzheimer's disease experience psychotic symptoms, which are associated with a more severe form of the disease and a faster cognitive decline, even before the onset of psychosis.

Neuroimaging studies reveal that Alzheimer's patients with psychosis show greater cortical impairments, including reduced gray matter volume and altered blood flow, and they have an accelerated accumulation of tau protein, suggesting distinct biological mechanisms compared to those without psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychosis in Alzheimer's disease. Murray, PS., Kumar, S., Demichele-Sweet, MA., et al.[2021]

In a study involving 487 patients with Alzheimer's dementia and psychosis, aripiprazole at 10 mg/day significantly improved psychotic symptoms and agitation compared to placebo, demonstrating its efficacy in this population.

While aripiprazole was generally safe, there were reports of cerebrovascular adverse events, particularly at higher doses, highlighting the need for careful monitoring when prescribing atypical antipsychotics to elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Mintzer, JE., Tune, LE., Breder, CD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9681874/

Effectiveness of KarXT (xanomeline-trospium) for cognitive ... ... xanomeline improved cognition in phase 2 trials in Alzheimer's disease and schizophrenia ... treatment effects in cognition and psychosis. Second, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05511363?intr=KarXT&viewType=Table&rank=2

A Study to Assess Efficacy and Safety of KarXT for ... The primary objective of the study is to evaluate relapse prevention in subjects with psychosis associated with Alzheimer's Disease treated with KarXT compared ...

3. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-New-Interim-Long-Term-Efficacy-Data-from-the-EMERGENT-4-Trial-Evaluating-KarXT-in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx

Long-term treatment with KarXT was associated ... KarXT (xanomeline-trospium) is an investigational muscarinic antipsychotic in development for the treatment of schizophrenia and psychosis ...

4. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20240076

The Impact of Xanomeline and Trospium Chloride on ... This benefit is not attributable to changes in symptoms, despite substantial evidence of efficacy for psychosis. Evaluation of xanomeline/ ...

5. psychopharmacologyinstitute.com psychopharmacologyinstitute.com/section/xanomeline-trospium-karxt-shows-efficacy-in-phase-3-trial-for-schizophrenia-2802-5700/

Xanomeline-Trospium (KarXT) Shows Efficacy in Phase 3 ... The key message is that they found that KarXT was effective for psychosis after 5 weeks of treatment. The study met its endpoint of a ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06947941

A Study to Evaluate Safety and Efficacy of KarXT + KarX ... Participants must not have psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia, eg, schizophrenia, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9719488/

Safety and tolerability of KarXT (xanomeline–trospium) in a ... KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X24007879

Efficacy, tolerability, and safety of xanomeline-trospium ... Other AEs, including psychosis, suicidal ideation, decreased appetite, sedation, and insomnia were not statistically significantly different between xanomeline- ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/216158Orig1s000OtherR.pdf

216158Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov KAR-031, a study of KarXT for the treatment of psychosis in Alzheimer's disease. In one of these 2 cases (Subject. , case narrative provided ...

10. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT06126224

Trial ID CN012-0027 | NCT06126224 - BMS Clinical Trials The primary objective of the study is to evaluate the efficacy of KarXT compared with placebo in the treatment of subjects with psychosis associated with AD.