ITI-1284 for Psychosis in Alzheimer's Disease

Recruiting at 12 trial locations

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Intra-Cellular Therapies, Inc.

Must not be taking: Psychotropics, CNS drugs

Disqualifiers: Schizophrenia, Bipolar, Suicide risk, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

370 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, flexible-dose study evaluating the efficacy, safety, and tolerability of ITI-1284 compared with placebo in the treatment of psychosis in patients with AD.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially those with psychotropic properties (affecting the mind) or those that impact the central nervous system. It's best to discuss your current medications with the study team to see if any changes are needed.

What data supports the effectiveness of the drug ITI-1284 for psychosis in Alzheimer's disease?

While there is no direct data on ITI-1284, similar treatments like memantine and haloperidol have shown some effectiveness in reducing psychotic symptoms in Alzheimer's patients. These studies suggest that targeting psychosis in Alzheimer's with medication can be beneficial. ^{1 2 3 4 5}

Is ITI-1284 (deuterated lumateperone) safe for humans?

Lumateperone, which is similar to ITI-1284, has shown a favorable safety profile in studies for schizophrenia, with no significant side effects like movement disorders or hormonal changes. It was well-tolerated in patients, with no major changes in vital signs or lab results. ^{6 7 8 9 10}

How is the drug ITI-1284 different from other treatments for psychosis in Alzheimer's disease?

ITI-1284, also known as deuterated lumateperone, is unique because it modulates multiple neurotransmitter systems (serotonin, dopamine, and glutamate) simultaneously, which is different from most other treatments that typically target only one system. This multi-target approach may offer benefits in treating psychosis in Alzheimer's disease with a favorable safety profile, avoiding significant side effects common in other antipsychotic medications. ^{4 6 11 12 13}

Eligibility Criteria

This trial is for people with Alzheimer's who are experiencing psychosis. Participants should be diagnosed with Alzheimer's Disease and currently have symptoms of psychosis. The study excludes individuals who don't meet the specific diagnostic criteria, those on certain medications, or anyone whose condition might interfere with the study.

Inclusion Criteria

Has a designated caregiver

My tests show signs of Alzheimer's disease.

Scoring ≥ 2 on any item of the BEHAVE-AD Part A. Paranoid and Delusional Ideation item and/or Part B. Hallucinations item at Screening and Baseline

Exclusion Criteria

Risk for suicidal behavior during the study or considered an imminent danger to themselves or others

I have been diagnosed with schizophrenia, schizoaffective disorder, or another psychotic disorder not related to Alzheimer's, or bipolar disorder.

I am not bedridden and do not have a severe unstable health condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Treatment

Participants receive either ITI-1284 or placebo in a double-blind manner

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

• ITI-1284

Trial Overview The trial is testing ITI-1284 to see if it helps treat psychosis in Alzheimer's patients compared to a placebo (a substance with no active drug). It’s a controlled test where patients are randomly chosen to receive either ITI-1284 or placebo without knowing which one they're getting.

Participant Groups

Group I: ITI-1284 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

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 313 individuals with moderate Alzheimer's disease, treatment with divalproex sodium (valproate) did not delay or prevent the emergence of agitation or psychosis compared to a placebo, indicating it may not be an effective intervention for these symptoms.

The valproate group experienced significant side effects, including increased somnolence, gait disturbances, and greater brain volume loss, suggesting that the risks of using valproate may outweigh any potential benefits in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. Tariot, PN., Schneider, LS., Cummings, J., et al.[2022]

An international expert panel emphasized a non-pharmacologic first-line approach for managing behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease, recommending caregiver training and environmental adaptations before considering medications.

For pharmacologic treatment, citalopram and analgesia were preferred for agitation, while risperidone was prioritized for psychosis, highlighting the need for careful assessment of underlying causes before medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus. Kales, HC., Lyketsos, CG., Miller, EM., et al.[2022]

In a 16-week study involving 53 patients with moderate to moderately severe Alzheimer's disease, memantine significantly improved behavioral disturbances, as indicated by a 4.6-point reduction in the Neuropsychiatric Inventory (NPI) score (p<0.01).

The study also found notable reductions in caregiver distress and specific symptoms such as depression, aberrant motor behavior, and agitation, suggesting memantine's efficacy in managing various neuropsychiatric symptoms associated with Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Memantine for treatment of behavioural disturbances and psychotic symptoms in moderate to moderately severe Alzheimer dementia: a naturalistic study in outpatient services in Austria]. Schmidt, R., Baumhackl, U., Berek, K., et al.[2013]

In a 6-week study involving 71 Alzheimer's patients, standard-dose haloperidol (2-3 mg/day) was found to be significantly more effective than both low-dose haloperidol (0.50-0.75 mg/day) and placebo in reducing psychosis and agitation, with response rates of 55%-60% for the standard dose.

While standard-dose haloperidol showed efficacy, it also led to a higher incidence of extrapyramidal side effects in some patients, suggesting that a cautious approach with a starting dose of 1 mg/day and gradual increases is advisable to minimize risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. Devanand, DP., Marder, K., Michaels, KS., et al.[2022]

Lumateperone (ITI-007) has a unique mechanism of action that targets multiple neurotransmitter systems, including serotonin, dopamine, and glutamate, making it a promising treatment for schizophrenia and potentially other psychiatric conditions.

It has shown a favorable safety profile, with no significant side effects like extrapyramidal symptoms or hyperprolactinemia, suggesting it could be a safer alternative to traditional antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. Mazza, M., Marano, G., Traversi, G., et al.[2021]

In a study involving 10 patients with schizophrenia, lumateperone (ITI-007) demonstrated a mean dopamine D2 receptor occupancy of 39% after a 60 mg dose, which is lower than most traditional antipsychotics, potentially leading to fewer side effects.

Lumateperone was well-tolerated with no significant adverse effects, such as motor disturbances or increased prolactin levels, suggesting it may offer a safer treatment alternative for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. Vanover, KE., Davis, RE., Zhou, Y., et al.[2020]

In a study of 301 outpatients with stable schizophrenia, lumateperone was found to be well tolerated, with only 45.5% experiencing treatment-emergent adverse events, most of which were mild or moderate, and a very low incidence of extrapyramidal symptoms (1.0%).

Patients switching to lumateperone showed significant improvements in metabolic parameters, such as reduced cholesterol and body weight, while maintaining stable schizophrenia symptoms, indicating its safety and efficacy compared to previous antipsychotic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. Correll, CU., Vanover, KE., Davis, RE., et al.[2021]

Lumateperone is a first-in-class investigational drug for schizophrenia that works by targeting multiple neurotransmitter systems, including serotonergic, glutamatergic, and dopaminergic pathways, which may help alleviate a wide range of symptoms associated with the disorder.

Clinical trials suggest that lumateperone has unique pharmacological properties that could significantly improve schizophrenia symptoms, and future studies are expected to provide more insights into its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of lumateperone tosylate for the treatment of schizophrenia. Vyas, P., Hwang, BJ., Brašić, JR.[2020]

Lumateperone (LUM) has been shown to significantly reduce the severity of schizophrenia symptoms compared to placebo, based on data from four clinical studies involving randomized controlled trials and an open-label trial.

LUM has a favorable safety and tolerability profile, exhibiting placebo-level rates of weight gain, metabolic changes, and extrapyramidal side effects, making it a strong candidate for first-line treatment in adults with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. Jawad, MY., Alnefeesi, Y., Ceban, F., et al.[2022]

Lumateperone tosylate is a first-in-class investigational drug that works through multiple neurotransmitter systems, including serotonergic, dopaminergic, and glutamatergic pathways, which may lead to rapid antidepressant effects.

In clinical trials, lumateperone demonstrated a safety profile similar to placebo, with significant improvements in both depressive and psychotic symptoms in patients with schizophrenia, indicating its potential for treating various mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: a new treatment approach for neuropsychiatric disorders. Kumar, B., Kuhad, A., Kuhad, A.[2019]

Lumateperone (Caplyta®) is a first-in-class medication that modulates serotonin, dopamine, and glutamate, making it a unique treatment option for schizophrenia and potentially other neuropsychiatric disorders.

Approved in December 2019 for schizophrenia in adults, lumateperone is also being studied for various conditions, including bipolar depression and Alzheimer's-related behavioral disorders, highlighting its broad therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lumateperone: First Approval. Blair, HA.[2021]

In a study analyzing participants from the Alzheimer's Disease Neuroimaging Initiative 2, it was found that individuals with misidentification psychosis experienced a significantly faster cognitive decline in Alzheimer's disease, with a rate of increase in cognitive scores that was doubled compared to nonpsychotic patients.

The findings suggest that misidentification may represent a distinct subtype of Alzheimer's disease, indicating that different types of psychosis could be linked to varying rates of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline. D'Antonio, F., Reeves, S., Sheng, Y., 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. United States pubmed.ncbi.nlm.nih.gov

Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

[Memantine for treatment of behavioural disturbances and psychotic symptoms in moderate to moderately severe Alzheimer dementia: a naturalistic study in outpatient services in Austria]. [2013]

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

A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. [2021]

9. England pubmed.ncbi.nlm.nih.gov

An evaluation of lumateperone tosylate for the treatment of schizophrenia. [2020]

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

Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. [2022]

11. Spain pubmed.ncbi.nlm.nih.gov

Lumateperone: a new treatment approach for neuropsychiatric disorders. [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Lumateperone: First Approval. [2021]

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

Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline. [2021]