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

Trial Summary

What is the purpose of this trial?

This is a Phase 3 global, multicenter, 52-week, open-label extension (OLE) rollover study for subjects completing study CN012-0026 or CN012-0027. Subjects (randomized or non-randomized) who complete the 38-week CN012-0026 or CN012-0027 study will be eligible to enroll in CN012-0028. The primary objective of the study is to assess the long-term safety and tolerability of KarXT in subjects with psychosis associated with Alzheimer's Disease.

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.

How is the drug KarXT different from other treatments for Alzheimer's-related psychosis?

KarXT is unique because it combines two components, xanomeline and trospium chloride, which work together to target symptoms of psychosis in Alzheimer's without the severe side effects often seen with traditional antipsychotics like haloperidol, which can worsen cognitive function and cause movement problems. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. 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]

2. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

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

Aripiprazole for the treatment of psychosis in patients with Alzheimer's disease: a randomized, placebo-controlled study. [2022]