KarXT for Psychosis in Alzheimer's Disease

(ADEPT-4 Trial)

Recruiting at 371 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of KarXT in adult participants with mild to severe Alzheimer's Disease (AD) with moderate to severe psychosis related to AD.

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.

How is the drug KarXT different from other drugs for psychosis in Alzheimer's disease?

KarXT is unique because it combines two components, xanomeline and trospium chloride, which work together to target specific brain receptors involved in psychosis, potentially offering a novel approach compared to traditional antipsychotics like aripiprazole and haloperidol that have limited efficacy and can cause severe side effects. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

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

My dementia is not due to schizophrenia or similar conditions.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients. [2020]

2. England 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. [2022]

3. England 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A pilot study of haloperidol treatment of psychosis and behavioral disturbance in Alzheimer's disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Psychosis in Alzheimer's disease. [2021]