ITI-1284 for Psychosis in Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Intra-Cellular Therapies, Inc.
Must not be taking: Psychotropics, CNS drugs
Disqualifiers: Schizophrenia, Bipolar, Suicide risk, others
Prior Safety Data
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.
12345Is 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.
678910How 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.
46111213Eligibility 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
+5 more
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.
+4 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: ITI-1284Experimental Treatment1 Intervention
Group II: PlaceboPlacebo Group1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical SiteHialeah, FL
Clinical SiteSarasota, FL
Clinical SiteNewport Beach, CA
Clinical SiteCoral Springs, FL
More Trial Locations
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Who Is Running the Clinical Trial?
Intra-Cellular Therapies, Inc.Lead Sponsor
References
Effects of Vitamin D Use on Outcomes of Psychotic Symptoms in Alzheimer Disease Patients. [2020]To identify medications that may prevent psychosis in patients with Alzheimer disease (AD).
Chronic divalproex sodium to attenuate agitation and clinical progression of Alzheimer disease. [2022]Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate).
Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus. [2022]ABSTRACTObjectives:Behavioral and psychological symptoms of dementia (BPSD) are nearly universal in dementia, a condition occurring in more than 40 million people worldwide. BPSD present a considerable treatment challenge for prescribers and healthcare professionals. Our purpose was to prioritize existing and emerging treatments for BPSD in Alzheimer's disease (AD) overall, as well as specifically for agitation and psychosis.
[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]We conducted an open, 16-week study on the efficacy of memantine on behavioral disturbances and psychotic symptoms in moderate to moderately severe Alzheimer s disease in daily routine. Fifty-three patients of 20 outpatient centers in Austria were recruited. The Neuropsychiatric Inventory (NPI) was defined as main outcome measure. After 16 weeks the total NPI score improved by 4,6 points (p
A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. [2022]The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease.
Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders. [2021]Lumateperone (ITI-007) is a tosylate salt with binding affinities to receptors implicated in the therapeutic actions of antipsychotic medications, including the serotonin 5HT2A receptors, dopamine D2 and D1 receptors and the serotonin transporter. It has a unique mechanism of action because it simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, implicated in serious mental illness. It can be considered a multi-target-directed ligand and a multifunctional modulator of serotoninergic system with possible precognitive, antipsychotic, antidepressant and anxiolytic properties. Lumateperone has been investigated as a novel agent for the treatment of schizophrenia, but it represents a new potential option for other psychiatric and neurological diseases, such as behavioural symptoms of dementia or Alzheimer's disease, sleep disturbances, bipolar depression. Besides, it has demonstrated a favourable safety profile without significant extrapyramidal side effects, hyperprolactinemia or changes in cardiometabolic or endocrine factors versus placebo. Additional studies are warranted to confirm and examine the benefit of lumateperone and possible therapeutic targets. This paper is a comprehensive and thorough summary of the most important findings and potential future role of this particular compound in personalized treatments.
Dopamine D2 receptor occupancy of lumateperone (ITI-007): a Positron Emission Tomography Study in patients with schizophrenia. [2020]Dopamine D2 receptor occupancy (D2RO) is a key feature of all currently approved antipsychotic medications. However, antipsychotic efficacy associated with high D2RO is often limited by side effects such as motor disturbances and hyperprolactinemia. Lumateperone (ITI-007) is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate in development for the treatment of schizophrenia and other disorders. The primary objective of the present study was to determine D2RO at plasma steady state of 60 mg ITI-007, a dose that previously demonstrated antipsychotic efficacy in a controlled trial, administered orally open-label once daily in the morning for two weeks in patients with schizophrenia (N = 10) and after at least a two-week washout period from standard of care antipsychotics. D2RO was determined using positron emission tomography with 11C-raclopride as the radiotracer. Mean peak dorsal striatal D2RO was 39% at 60 mg ITI-007 occurring 1 h post-dose. Lumateperone was well-tolerated with a favorable safety profile in this study. There were no clinically significant changes in vital signs, ECGs, or clinical chemistry laboratory values, including prolactin levels. There were no adverse event reports of akathisia or other extrapyramidal motor side effects; mean scores on motor function scales indicated no motor disturbances with lumateperone treatment. This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia. If approved, lumateperone may provide a new and safe treatment option for individuals living with schizophrenia.
Safety and tolerability of lumateperone 42 mg: An open-label antipsychotic switch study in outpatients with stable schizophrenia. [2021]Lumateperone is a mechanistically novel agent FDA-approved for the treatment of schizophrenia. Efficacy and favorable tolerability of lumateperone were demonstrated in 2 short-term placebo-controlled studies in patients with schizophrenia. This open-label study investigated the short-term safety/tolerability of lumateperone in outpatients with stable schizophrenia switched from previous antipsychotic treatment.
An evaluation of lumateperone tosylate for the treatment of schizophrenia. [2020]Introduction: Schizophrenia, a devastating disorder with onset in adolescence or young adulthood, afflicts 1% of the population leading to severe social, educational, and occupational impairments. Lumateperone is a first-in-class investigational drug under development for the treatment of multiple neuropsychiatric and neurodegenerative disorders including schizophrenia. Its unique receptor affinity profile together with synergistic modulation of serotonergic, glutamatergic, and dopaminergic pathways imparts efficacy over a broad-spectrum of symptoms associated with schizophrenia.Areas covered: This narrative drug evaluation includes a review of lumateperone tosylate (lumateperone, ITI-007, ITI-722, Intra-Cellular Therapies, Inc.) for patients with schizophrenia. This review describes the receptor affinity profile, pharmacodynamics, pharmacokinetics, distribution, metabolism, and clinical trials that address how lumateperone could potentially emerge as an important therapeutic option for schizophrenia patients.Expert opinion: The unique pharmacological properties of lumateperone may provide the key to dramatically ameliorate the symptoms of schizophrenia as indicated by some clinical trials. Future clinical trials may be enhanced by the administration of more comprehensive long-term behavioral measures and utilization of molecular imaging to confirm the target engagement of the many possible sites of action. The results of ongoing and future studies will provide the evidence to determine if lumateperone will revolutionize the therapy of schizophrenia.
Lumateperone for the Treatment of Adults With Schizophrenia: a Systematic Review. [2022]Lumateperone (LUM) is the U.S. Food and Drug Administration approved atypical antipsychotic agent for adults with schizophrenia (SCZ) and bipolar depression (for both bipolar I and bipolar II disorder as as monotherapy or as adjunctive treatment to lithium or valproate). LUM simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. The foregoing pleiotropic mechanism of action is predictive of therapeutic benefits across multiple domains of psychopathology in SCZ (i.e., positive, negative, cognitive, and prosocial symptoms). Herein, the overarching aim is to synthesize the extant literature reporting on the efficacy, safety, and tolerability of LUM in adults with SCZ.
Lumateperone: a new treatment approach for neuropsychiatric disorders. [2019]Lumateperone tosylate (ITI-007 tosylate, ITI-722) is a first-in-class investigational drug which acts syn-ergistically through multiple systems (serotonergic, dopaminergic and glutamatergic), thus representing a unique approach for the therapeutic management of a range of neuropsychiatric disorders. It possesses a potent antagonistic activity at 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptors and also binds to dopamine (D1, D2) receptors with partial agonism at presynaptic D2 receptors and postsynaptic antagonism. Further, preclinical data demonstrated that lumateperone uniquely acts as an indirect modulator of glutamatergic phosphoprotein with D1-dependent augmentation of both NMDA and AMPA activity via the mammalian target of rapamycin (mTOR) pathway, mechanisms thought to predict potent and rapid antidepressant effects. Previous results of schizophrenia efficacy studies found robust improvements in depressive as well as psychotic symptoms for those patients who were comorbidly depressed. In various clinical trials to date, the safety profile of lumateperone was found to be similar to that of placebo. These promising results and strong performance in phase II studies point to the potential of lumateperone to display potent and rapid antidepressant effects in patients suffering from a range of mood disorders. Currently, this novel drug is in phase III of its clinical development for schizophrenia, agitation associated with dementia and bipolar depression.
Lumateperone: First Approval. [2021]Lumateperone (Caplyta®) is a novel, orally available agent developed by Intra-Cellular Therapies (under a license from Bristol-Myers Squibb) for the treatment of schizophrenia and other neuropsychiatric and neurological disorders. Lumateperone is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate. In December 2019, lumateperone received its first global approval in the USA for the treatment of schizophrenia in adults. The drug is also under clinical development for bipolar depression, behavioural disorders associated with dementia and Alzheimer's disease, sleep maintenance insomnia and major depressive disorders. This article summarizes the milestones in the development of lumateperone leading to this first approval for the treatment of schizophrenia.
Misidentification Subtype of Alzheimer's Disease Psychosis Predicts a Faster Cognitive Decline. [2021]The presence of psychosis is associated with a more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. We analyzed data on Alzheimer's Disease Neuroimaging Initiative 2 participants with late mild cognitive impairment or AD, and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale scores using a semimechanistic logistic model with a mixed effects-based approach, which accounted for dropout and adjusted for baseline Mini Mental State Examination scores. The covariate model included psychosis subtypes, age, gender, education, medications, and Apolipoprotein E epsilon 4 (Apo-e ε4 genotype). We found that the Alzheimer's Disease Assessment Scale-Cognitive Subscale rate of increase was doubled in misidentification (βr,misid_subtype  = 0.63, P = 0.031) and mixed (both subtypes; βr,mixed_subtype  = 0.70, P = 0.003) when compared with nonpsychotic (or paranoid) patients, suggesting that the misidentification subtype may represent a distinct AD sub-phenotype associated with an accelerated pathological process.