What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease that modulate cholinergic neurotransmission, such as muscarinic receptor agonists and antagonists, can have several side effects. These may include gastrointestinal issues like nausea, vomiting, and diarrhea, as well as cardiovascular effects such as bradycardia (slow heart rate) and hypotension (low blood pressure). Cognitive side effects like confusion and dizziness are also possible. Additionally, treatments like KarXT, which combine different agents to balance cholinergic activity, may present a unique profile of side effects, including dry mouth, constipation, and urinary retention due to the antagonistic component.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Alzheimer's Disease that focus on modulating cholinergic neurotransmission. Donepezil, rivastigmine, and galantamine are cholinesterase inhibitors that increase acetylcholine levels in the brain, aiming to improve cognitive function. Memantine, an NMDA receptor antagonist, is also approved and works by regulating glutamate activity to protect brain cells. These treatments primarily address cognitive symptoms, whereas KarXT, a combination of xanomeline and trospium, is being studied specifically for its potential to reduce psychosis symptoms in Alzheimer's patients by modulating muscarinic receptors.

What other types of research exist?

Promising novel alternatives to KarXT for treating psychosis in Alzheimer's Disease patients include: 1) Pimavanserin, a selective serotonin inverse agonist and antagonist preferentially targeting 5-HT2A receptors, which has shown efficacy in reducing psychosis in Parkinson's Disease and is being investigated for AD psychosis. 2) Brexpiprazole, a serotonin-dopamine activity modulator, which has shown potential in treating agitation and psychosis in AD. 3) Antipsychotic agents like aripiprazole and quetiapine, which are being studied for their efficacy and safety in managing psychosis in AD patients. These alternatives are in various stages of clinical trials and may offer new options for managing psychosis in AD by 2024.

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KarXT for Alzheimer's-Related Psychosis (ADEPT-2 Trial)

Verified Trial

Phase 3

Recruiting

Research Sponsored by Karuna Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male or female aged 55 to 90 years at Screening

Can understand the nature of the trial and protocol requirements and provide informed consent or assent before any study assessments are performed

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline and end of treatment (up to 14 weeks)

Awards & highlights

Pivotal Trial

Summary

This trial is testing KarXT, a medication for adults aged 55-90 with Alzheimer's Disease and severe psychosis. The goal is to see if KarXT can reduce symptoms like hallucinations and delusions by balancing brain chemicals.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not specified here, common side effects of treatments like KarXT may include dizziness, nausea, changes in appetite or weight, sleep disturbances, or mood swings. Each person might react differently.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 55 and 90 years old.

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I understand the trial details and can give informed consent.

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I have been diagnosed with early or likely Alzheimer's disease.

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

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I have had symptoms of psychosis for at least 2 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline and end of treatment (up to 14 weeks)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline and end of treatment (up to 14 weeks)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline and end of treatment (up to 14 weeks) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from Baseline to End of Treatment in the Neuropsychiatric Inventory-Clinician: Hallucinations and Delusions (NPI-C: H+D) score

Secondary study objectives

Change from Baseline to End of Treatment in the Clinical Global Impressions-Severity (CGI-S) scale

Change from Baseline to End of Treatment in the Cohen-Mansfield Agitation Inventory (CMAI) score

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: KarXTExperimental Treatment1 Intervention

Xanomeline and Trospium Chloride Capsules

Group II: PlaceboPlacebo Group1 Intervention

Placebo Capsules

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Alzheimer's Disease (AD) often target the cholinergic system, amyloid-beta plaques, and tau protein tangles. Cholinesterase inhibitors (e.g., donepezil, rivastigmine) increase acetylcholine levels by inhibiting its breakdown, which can help improve cognitive function. KarXT, a combination of xanomeline (a muscarinic receptor agonist) and trospium (a muscarinic receptor antagonist), aims to modulate cholinergic neurotransmission to reduce psychosis symptoms in AD patients. Additionally, treatments like anti-amyloid antibodies (e.g., aducanumab) target amyloid-beta plaques to slow disease progression, while tau protein stabilizers aim to prevent neurofibrillary tangles. These mechanisms are crucial as they address different pathological aspects of AD, potentially improving symptoms and slowing disease progression.

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer’s Disease.