KarXT for Alzheimer's-Associated Psychosis

(ADEPT-1 Trial)

Recruiting at 219 trial locations

Overseen By Marc Agronin, Site 1010

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karuna Therapeutics

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: MAO inhibitors, Anticonvulsants

Disqualifiers: Bipolar, Schizophrenia, Severe renal impairment, 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: 38 weeks

380 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KarXT (a combination of xanomeline and trospium chloride) for individuals with Alzheimer's Disease who experience psychosis, including symptoms like hallucinations or delusions. The goal is to determine if KarXT can prevent these symptoms from worsening compared to a placebo (a pill with no active medicine). Participants should have experienced psychotic symptoms for at least two months and have Alzheimer's Disease. Those who have lived in the same place for at least six weeks and can move around independently or with assistance might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial requires that if you are taking a cholinesterase inhibitor or memantine, you must have been on a stable dose for 6 weeks before joining and continue that dose during the study. Some other medications, like certain antidepressants, need to be stable for at least 8 weeks before joining. You may need to stop or adjust other medications, so it's best to discuss with the trial team.

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

Research shows that KarXT, a combination of xanomeline and trospium chloride, is generally well tolerated. Studies indicate that the side effects align with the known mechanisms of these drugs in the brain, making them expected and manageable.

Some reports mention unwanted effects, but these align with existing knowledge about the drugs. Importantly, KarXT has also been studied in conditions like schizophrenia, providing more information about its safety.

Overall, the treatment has been tested in people and is considered well-tolerated based on current research. However, like any treatment, side effects can occur, so discussing these with the trial team is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for Alzheimer's-associated psychosis, which typically involves antipsychotics that can have significant side effects, KarXT offers a novel approach by combining xanomeline and trospium chloride. Xanomeline targets muscarinic receptors in the brain, which are involved in cognitive function and psychosis, while trospium chloride helps minimize peripheral side effects, making it potentially safer. Researchers are excited because this dual-action mechanism could offer symptom relief with fewer side effects, improving quality of life for patients.

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

Research shows that KarXT, a combination of xanomeline and trospium chloride, may help treat psychosis in people with Alzheimer's disease. In this trial, participants will receive either KarXT or a placebo. Earlier studies found that KarXT can improve thinking and reduce symptoms in schizophrenia. For Alzheimer's-related psychosis, KarXT has been tested to see if it can prevent symptoms from returning, and results suggest it works better than a placebo. This treatment targets brain areas involved in memory and thinking, which often function poorly in Alzheimer's patients. While more research is needed, early results are promising for those dealing with these challenging symptoms. ^{1 3 4 6 7}

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 people aged 55-90 with Alzheimer's-related psychosis, able to move independently (with or without aid), and have a caregiver. They must not be pregnant, agree to use contraception if applicable, and have been on stable doses of certain medications for six weeks. Exclusions include recent major depression with psychosis, stroke history within the last year, COVID-19 infection within two weeks before screening, or prior KarXT exposure.

Inclusion Criteria

I can visit the clinic as needed and follow all study instructions.

Clinical Global Impressions-Severity (CGI-S) scale with a score ≥4 (moderate) at Screening (Visit 1A). CGI-S requires the assessor to consider aspects of the psychosis prior to providing a global assessment of severity. These aspects include hallucinations and delusions.

I've been on a stable dose of my Alzheimer's medication for 6 weeks.

Exclusion Criteria

Significant or severe medical conditions including pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the Investigator, could jeopardize the safety of the subject, ability to complete or comply with the study procedures or validity of the study results

You have any of the following conditions: heart problems, liver diseases, high risk for urinary retention, narrow-angle glaucoma, or serious constipation in the last 6 months. You also have a history or high risk of long QT syndrome, or have a positive urine test for certain substances without medical approval. Additionally, you have an implantable cardiac defibrillator, or have had a heart attack within the last 6 months. You may also be excluded if you have a history of irritable bowel syndrome, show signs of suicidal behavior, have any abnormal physical examination or laboratory results during screening, or have HIV.

I cannot stop taking a medication that would interfere with the study.

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 in a double-blind manner to evaluate relapse prevention in psychosis associated with Alzheimer's Disease

38 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT
• Placebo

Trial Overview The study tests KarXT against a placebo in preventing relapse of psychosis symptoms in Alzheimer's patients over 38 weeks. It's randomized and double-blind meaning neither participants nor researchers know who gets the real treatment versus placebo until after the results are collected.

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

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 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]

The prevalence of psychosis in Alzheimer's disease (PoAD) was found to be 7.3%, with a cumulative incidence increasing over 24 months, indicating that psychotic symptoms are common in Alzheimer's patients.

Patients with PoAD experience faster functional decline and have a significantly increased mortality risk (over two times higher) compared to those without psychosis, suggesting that PoAD represents a more severe form of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychosis of Alzheimer disease: prevalence, incidence, persistence, risk factors, and mortality. Vilalta-Franch, J., López-Pousa, S., Calvó-Perxas, L., 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]

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 ... Indeed, xanomeline has been shown to improve cognition in patients with AD [21] and in a small phase 2 proof-of-concept study in schizophrenia [ ...

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

NCT06947941 | A Study to Evaluate Safety and Efficacy of ... 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. bmsstudyconnect.com bmsstudyconnect.com/no/en/clinical-trials/NCT06126224.html

24 March, 2025 - BMS Clinical Trials A study to assess efficacy and safety of KarXT for the treatment of psychosis associated with Alzheimer's disease.

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. 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 ...

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

216158Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov The Division of Psychiatry (DP) requests assistance on an original NDA (xanomeline and trospium chloride) for the treatment of 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.