KarXT for Alzheimer's-Related Psychosis

(ADEPT-3 Trial)

Recruiting at 204 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: Severe medical conditions, 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

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called KarXT (also known as Cobenfy or Xanomeline/Trospium chloride) to determine its safety and tolerability for individuals with Alzheimer's-related psychosis. The goal is to understand KarXT's effects over an extended period. It is intended for those who have completed specific earlier studies (CN012-0026 or CN012-0027) and have Alzheimer's-related psychosis. Participants must have a caregiver available for about 10 hours a week. As a Phase 3 trial, this represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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 study team or your doctor.

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 being tested for safety in treating psychosis related to Alzheimer's disease. Earlier studies found that most participants tolerated the treatment well. Common side effects included dry mouth and constipation, but these were usually mild and did not prevent most patients from continuing the treatment.

Regarding more serious side effects, no major differences appeared compared to a placebo, which is similar to a sugar pill. This indicates that KarXT did not cause more serious issues than the placebo. As this is a Phase 3 trial, KarXT has already undergone earlier stages to assess its safety and effectiveness, providing substantial information supporting its safety for individuals. However, everyone can react differently to a treatment, so staying in touch with a healthcare provider is important if one decides to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Alzheimer's-related psychosis, which typically include antipsychotic medications, KarXT uses a novel combination of xanomeline and trospium chloride. This treatment is unique because xanomeline targets muscarinic receptors, which are involved in regulating neurotransmitters associated with psychosis, while trospium chloride helps reduce peripheral side effects. Researchers are excited about KarXT because it offers a new mechanism of action that could potentially improve symptoms with fewer side effects compared to current antipsychotic options.

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

Studies have shown that KarXT, a combination of xanomeline and trospium chloride, effectively treats psychosis related to Alzheimer's disease. Research indicates that KarXT targets specific brain areas to reduce symptoms like hallucinations and delusions. In earlier studies, patients taking KarXT showed noticeable improvements compared to those on a placebo, which contains no active medicine. This trial will further evaluate KarXT's effectiveness, suggesting it could be a promising treatment for Alzheimer's patients experiencing psychosis. ^{1 4 6 7 8}

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 to 90 with psychosis linked to Alzheimer's who finished the KAR-031 study. They must understand the study, give consent (or have a representative do so), and have a caregiver. Those with severe medical issues or recent significant test abnormalities can't join.

Inclusion Criteria

Must have completed study KAR-031 or KAR-032

I have someone who helps me for about 10 hours a week.

I was between 55 and 90 years old when I joined the KAR-031 or KAR-032 study.

Exclusion Criteria

Subjects participating in another investigational drug or device study or planning on participating in another clinical study during the duration of KAR-033

I don't have any health issues that could make the trial unsafe for me.

Significant or severe medical conditions 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label extension

Participants receive KarXT to assess long-term safety and tolerability

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KarXT

Trial Overview The trial tests KarXT's long-term safety and tolerability in treating psychosis in Alzheimer's patients over a year. It’s an extension of a previous study where participants continue receiving KarXT after completing the initial phase.

How Is the Trial Designed?

Group I: KarXT Experimental Treatment 1 Intervention

Xanomeline and Trospium Chloride 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 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]

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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9776782/

Xanomeline and Trospium: A Potential Fixed Drug ... ... psychosis and cognitive impairment in schizophrenia: Phase I studies. ACNP ... A study to assess efficacy and safety of KarXT in acutely psychotic hospitalized ...

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

216158Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov Safety Update. 2 Study 031 investigates KarXT for Alzheimer's psychosis. 20 subjects reported exposed as of the cut-off date in 120-Day ...

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- ...