ITI-1284 for Agitation in Dementia

Recruiting at 12 trial locations

Overseen By ITI Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Intra-Cellular Therapies, Inc.

Disqualifiers: Schizophrenia, Bipolar, Major depression, others

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

Compensation: Varies

Number of Visits: Unknown

320 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, placebo-controlled, flexible-dose study of the efficacy, safety, and tolerability of ITI-1284 in patients with agitation associated with Alzheimer's dementia

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if your agitation symptoms are due to your current medications, you might not be eligible to participate.

What evidence supports the effectiveness of the drug ITI-1284 for agitation in dementia?

Lumateperone, a component of ITI-1284, has shown potential in treating behavioral symptoms of dementia and Alzheimer's disease due to its unique action on brain chemicals like serotonin and dopamine. It has been effective in improving symptoms in other psychiatric conditions, such as schizophrenia and bipolar depression, with a good safety profile similar to placebo. ^{1 2 3 4 5}

How does the drug ITI-1284 differ from other drugs for agitation in dementia?

ITI-1284, also known as deuterated lumateperone, is unique because it is a novel agent being researched for its potential to treat behavioral and psychological symptoms associated with dementia, unlike traditional treatments like antipsychotics and serotonin-dopamine antagonists, which have limited efficacy and can cause serious side effects. ^{5 6 7 8 9}

Eligibility Criteria

This trial is for individuals with Alzheimer's who experience agitation or psychosis. Participants should be in a stable condition and have a caregiver available. People with other types of dementia, unstable medical conditions, or those using certain medications that affect the brain may not qualify.

Inclusion Criteria

Has clinically meaningful agitation defined as a Neuropsychiatric Inventory-Agitation/Aggression (NPI-AA) domain total score of ≥ 4 at both Screening and Baseline

Has Mini-Mental State Examination, 2nd Edition™: Standard Version (MMSE-2®:SV) score of 6 to 24 at Screening

Meets all criteria for agitation according to the International Psychogeriatric Association (IPA) consensus definition

Exclusion Criteria

Has a significant risk for suicidal behavior during the course of their participation in the study, or is considered to be an imminent danger to themselves or others, in the opinion of the investigator, and/or as assessed by Columbia Suicide Severity Rating Scale (C-SSRS); or the patient has had 1 or more suicide attempts within the 2 years prior to Screening

The patient has known hypersensitivity or intolerance to ITI-1284 or lumateperone, or to any of their excipients

My agitation is not due to drugs, environment, substance abuse, or other health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Double-blind Treatment

Participants are randomized to receive either ITI-1284 or placebo for 12 weeks

12 weeks

Safety Follow-up

Participants are monitored for safety approximately 30 days after the last dose of study drug

4 weeks

Treatment Details

Interventions

• ITI-1284

Trial Overview The study tests ITI-1284's effectiveness and safety against placebo in managing Alzheimer's-related agitation. Patients are randomly assigned to receive either ITI-1284 or a placebo without knowing which one they're getting.

Participant Groups

Group I: ITI-1284 Experimental Treatment 1 Intervention

ITI-1284 10 mg or 20 mg rapidly disintegrating tablet, taken once daily, sublingual administration

Group II: Placebo Placebo Group 1 Intervention

Placebo rapidly disintegrating tablet, taken once daily, sublingual administration

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Findings from Research

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 multicenter trial involving 153 nursing home residents with dementia, divalproex sodium (target dose of 750 mg/day) showed no significant benefit in reducing agitation compared to placebo over 6 weeks.

Safety and tolerability measures indicated no clinically important differences between divalproex and placebo, contradicting earlier studies that suggested potential benefits for treating agitation in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial. Tariot, PN., Raman, R., Jakimovich, L., et al.[2017]

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]

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]

Current treatments for behavioral and psychological symptoms in dementia, such as cholinesterase inhibitors and antipsychotics, show limited effectiveness and can lead to serious side effects, highlighting the need for new options.

Novel agents like dextromethorphan/quinidine and lumateperone have shown promising results in clinical trials and are generally well tolerated, suggesting they could be effective alternatives for managing these symptoms in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Agents in Development for Treating Behavioral and Psychological Symptoms Associated with Dementia. Ahmed, M., Malik, M., Teselink, J., et al.[2022]

In a study involving 176 hospitalized dementia patients, both tiapride and melperone were found to be equally effective in reducing psychomotor agitation, with a response rate of 74.36% for both treatments.

The safety profile of tiapride was comparable to melperone, with no significant changes in vital signs or serious adverse events, indicating that tiapride is a safe alternative for managing agitation in dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the efficacy of psychopharmacological treatment of psychomotoric restlessness in dementia: clinical evaluation of tiapride. Gutzmann, H., Kühl, KP., Kanowski, S., et al.[2013]

Haloperidol showed no overall improvement in agitation among demented patients compared to placebo, although it may help control aggression in some cases.

Patients treated with haloperidol experienced more side effects and higher dropout rates, particularly with higher doses (over 2 mg per day) and prolonged therapy (more than 3-6 weeks), indicating safety concerns with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haloperidol for agitation in dementia. Lonergan, E., Luxenberg, J., Colford, J.[2018]

In a study of 18 outpatients with dementia over 6 weeks, the serotonin dopamine antagonist perospirone (PER) significantly improved aggressive and agitated behaviors, particularly reducing verbal outbursts and agitation scores.

The study found PER to be safe for elderly patients, with only 2 participants dropping out due to mild adverse effects and no serious side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of perospirone in the management of aggressive behavior associated with dementia. Sato, S., Mizukami, K., Moro, K., et al.[2012]

In a 6-week study involving 6 patients with dementia, perospirone effectively reduced aggressive and agitated behaviors, with significant improvements observed within just 2 weeks.

The maximum benefit was noted at a mean dose of 9.0 mg/day, and importantly, no severe adverse effects were reported, indicating that perospirone is a safe treatment option for elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of perospirone on aggressive behavior associated with dementia. Sato, S., Mizukami, K., Moro, K., et al.[2012]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial. [2017]

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

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

4. Spain pubmed.ncbi.nlm.nih.gov

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

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

Current Agents in Development for Treating Behavioral and Psychological Symptoms Associated with Dementia. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Measuring the efficacy of psychopharmacological treatment of psychomotoric restlessness in dementia: clinical evaluation of tiapride. [2013]

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

Haloperidol for agitation in dementia. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy of perospirone in the management of aggressive behavior associated with dementia. [2012]

9. Australia pubmed.ncbi.nlm.nih.gov

Beneficial effects of perospirone on aggressive behavior associated with dementia. [2012]