KarXT for Alzheimer's-Related Psychosis

(ADEPT-2 Trial)

Recruiting at 159 trial locations

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Disqualifiers: Bipolar, Schizophrenia, Major depression, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called KarXT for individuals with Alzheimer's Disease who experience moderate to severe psychosis, such as hallucinations or delusions. The goal is to determine if KarXT can effectively reduce these symptoms compared to a placebo. Suitable candidates have experienced Alzheimer's-related psychotic symptoms for at least two months and currently reside in a stable setting, such as their own home or an assisted-living facility. Participants will receive either the experimental treatment, KarXT, or a placebo to compare outcomes. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment development.

Will I have to stop taking my current medications?

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

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

Research has shown that KarXT, a combination of xanomeline and trospium chloride, may alleviate symptoms in people with schizophrenia. It generally has a safety profile that most people can tolerate without major issues.

In studies, KarXT demonstrated potential benefits for thinking problems and psychosis. Although limited safety data exists for its use in Alzheimer's-related psychosis, KarXT is undergoing advanced clinical trials. This indicates researchers consider it safe enough for further testing in people.

Clinical trials are crucial to ensure treatments are effective and safe. Participants receive close monitoring to manage any side effects that may occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's-related psychosis?

Unlike standard treatments for Alzheimer's-related psychosis, which often involve antipsychotics like risperidone or olanzapine, KarXT is unique because it combines two active ingredients, xanomeline and trospium chloride, to specifically target muscarinic receptors in the brain. This approach is different because it aims to alleviate psychotic symptoms without the side effects typically associated with dopamine receptor blockers, such as movement disorders or cognitive decline. Researchers are excited about KarXT as it has the potential to offer a safer and more effective alternative for managing psychosis in Alzheimer's patients, addressing a significant unmet need in this area.

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

Research shows that KarXT, a combination of xanomeline and trospium chloride, may help treat psychosis in people with Alzheimer's disease. In earlier studies, KarXT effectively reduced symptoms such as hallucinations and delusions, which are common in Alzheimer's-related psychosis. Participants in this trial will receive either KarXT or a placebo. The treatment targets specific brain areas involved in these symptoms. Initial results indicated that patients improved significantly compared to those who took a placebo, suggesting that KarXT could be a promising treatment for psychosis in Alzheimer's patients. ^{1 2 3 4 6}

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 men and women aged 55 to 90 with mild to severe Alzheimer's Disease who experience moderate to severe psychosis. Participants must understand the study, have a caregiver interacting with them at least 10 hours weekly, and meet specific criteria for psychotic symptoms and cognitive assessment scores.

Inclusion Criteria

Living at the same home or residential assisted-living facility for a minimum of 6 weeks before Screening

I have someone who can be with me for at least 10 hours a week.

I have Alzheimer's with strong hallucinations or delusions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KarXT or placebo for the treatment of psychosis associated with Alzheimer's Disease

14 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 trial is testing KarXT against a placebo in individuals with Alzheimer's-related psychosis. It aims to see if KarXT can better reduce hallucinations and delusions compared to a non-active treatment. The effectiveness will be measured using the NPI-C: Hallucinations and Delusions score.

How Is the Trial Designed?

Group I: KarXT Experimental Treatment 1 Intervention

Xanomeline and Trospium Chloride Capsules

Group II: Placebo Placebo Group 1 Intervention

Placebo Capsules

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]

In a 10-week study involving 208 patients with Alzheimer's Disease-associated psychosis, aripiprazole demonstrated significantly greater improvements in psychotic symptoms compared to placebo, particularly on the Brief Psychiatric Rating Scale (BPRS).

Aripiprazole was found to be safe and well-tolerated, with mild to moderate adverse effects, and no significant differences in extrapyramidal symptoms or other serious side effects compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study. De Deyn, P., Jeste, DV., Swanink, R., et al.[2022]

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]

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 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 ... Thus, although the patient population in EMERGENT-1 clearly exhibited psychosis or positive symptoms, they may not necessarily exhibit ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06947941

A Study to Evaluate Safety and Efficacy of KarXT + KarX ... The purpose of this study is to evaluate KarXT + KarX-EC as a treatment for psychosis associated with Alzheimer's disease. Official Title. A Phase 3, Randomized ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/216158Orig1s000IntegratedR.pdf

216158Orig1s000 - accessdata.fda.gov ... xanomeline free base and trospium chloride salt. Doses will be presented in milligrams, with xanomaline presented first followed by trospium ...

4. 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.

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ps.20250013

Integrating Cobenfy Into Clinical Practice It highlights the potential of novel pharmacologic approaches to schizophrenia (and related conditions such as bipolar I disorder, psychosis in ...

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

Efficacy, tolerability, and safety of xanomeline-trospium ... Xanomeline-trospium is an effective treatment for schizophrenia with a unique tolerability profile, potentially addressing unmet needs.