ITI-1284 for Healthy Volunteers

Overseen By ITI Clinical Trials

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Intra-Cellular Therapies, Inc.

Disqualifiers: Cardiac, Hepatic, Renal, Neurologic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ITI-1284 (also known as deuterated lumateperone or ITI-1284-ODT-SL) to examine its interaction with specific brain receptors related to dopamine and serotonin. These receptors play a role in mood and brain function, and understanding this interaction might aid in developing future treatments for mental health conditions. Participants will be divided into groups to receive different doses of ITI-1284. The trial seeks healthy individuals who are comfortable staying in a hospital research unit for a period and meet certain health criteria, such as a specific body mass index (BMI) and weight. As a Phase 1 trial, participants will be among the first to receive this new treatment, assisting researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study is for healthy volunteers, it is likely that participants should not be on any regular medications.

Is there any evidence suggesting that ITI-1284 is likely to be safe for humans?

Research has shown that ITI-1284 has been tested on healthy individuals, including those aged 65 and older. These studies found no major safety problems, suggesting that ITI-1284 is generally safe for humans. However, the treatment remains in the early stages of testing. Trials at this stage often assess a treatment's safety for people, indicating that more research is needed to fully understand its safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ITI-1284 because it represents a potential shift in how we understand and treat neurological conditions. Unlike traditional treatments that primarily focus on symptom management, ITI-1284 is being explored for its novel mechanism of action using radioligands like [11C]-raclopride, [11C]-MDL100907, and [11C]-DASB, which may provide more precise targeting of brain receptors. This could lead to more effective treatments with potentially fewer side effects compared to standard medications. By using these innovative radioligands, ITI-1284 might offer insights into receptor activity in the brain, paving the way for more personalized and effective treatment strategies.

What evidence suggests that ITI-1284 could be effective for receptor occupancy in healthy volunteers?

Research has shown that ITI-1284, a modified form of lumateperone, may help treat conditions like schizophrenia and bipolar depression. In earlier studies, a 42 mg dose of lumateperone effectively reduced symptoms of these mental health disorders. ITI-1284 absorbs quickly and remains stable in the body, suggesting it might help manage symptoms of behavioral issues in dementia. This treatment works by affecting key brain receptors related to mood and behavior. These findings strongly support further exploration of ITI-1284 for various mental health conditions.

In this trial, healthy volunteers will receive different dosages of ITI-1284, ranging from 10 mg to 20 mg, across various cohorts to study its effects and absorption. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy individuals who can participate in a study to understand how ITI-1284, a potential medication, works in the brain. Participants will be placed into one of two groups to receive different doses of the drug and undergo special brain scans before and after taking it.

Inclusion Criteria

BMI inclusive of 18-32 kg/m2 at screening and a minimum weight of 50 kg

Willingness to remain in the hospital research unit for the duration of the inpatient period

Exclusion Criteria

Clinically significant abnormality within 2 years of Screening that may place the subject at risk or interfere with study outcome variables

Clinically significant abnormal findings in vital sign assessments at Screening

History of psychiatric condition that may be detrimental to participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A

Evaluation of D2 receptor occupancy for ITI-1284 at two dose levels

1 day

1 visit (in-person)

Part B

Evaluation of 5HT-2A receptor and SERT occupancy for ITI-1284 at one dose level

1 day

1 visit (in-person)

Part C (optional)

Evaluation of the time course of receptor occupancy of ITI-1284 on the D2 or 5-HT2A receptor at one dose level

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ITI-1284

Trial Overview The trial is testing two doses of ITI-1284 (20 mg and 10 mg) to see how much it occupies dopamine D2 receptors in the brain. It's an open-label study where everyone knows what treatment they're getting, involving baseline and postdose PET/CT scans.

How Is the Trial Designed?

Group I: Cohort C: 20 mg ITI-1284 Experimental Treatment 1 Intervention

Radioligand: \[11C\]-MDL100907 or \[11C\]-raclopride

Group II: Cohort B2: 20 mg ITI-1284 Experimental Treatment 1 Intervention

Radioligand: \[11C\]-DASB

Group III: Cohort B1: 20 mg ITI-1284 Experimental Treatment 1 Intervention

Radioligand: \[11C\]-MDL100907

Group IV: Cohort A2: 20 mg ITI-1284 Experimental Treatment 1 Intervention

Radioligand: \[11C\]-raclopride

Group V: Cohort A1: 10 mg ITI-1284 Experimental Treatment 1 Intervention

Radioligand: \[11C\]-raclopride

Who Is Running the Clinical Trial?

Intra-Cellular Therapies, Inc.

Lead Sponsor

Trials

42

Recruited

10,700+

Published Research Related to This Trial

A once-daily therapy combining didanosine, lamivudine, and nevirapine was administered to HIV-infected intravenous drug users, showing strong immunological and antiviral effects over the first 24 weeks.

The regimen demonstrates potential as an effective treatment option for managing HIV in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nevirapine/didanosine/lamivudine once daily in HIV-1-infected intravenous drug users. Staszewski, S., Haberl, A., Gute, P., et al.[2013]

In a study of 14 patients who failed treatment with lamivudine and then didanosine, minor HIV-1 populations were found to harbor the M184I/V mutation, even when direct sequencing showed wild-type virus, indicating that standard testing may miss these resistant strains.

The presence of M184I/V mutations in minor viral populations did not appear to be a common pathway to resistance against didanosine, as most patients did not show re-emergence of these mutations after switching therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. Svedhem, V., Bergroth, T., Lidman, K., et al.[2013]

In a study of 104 HIV-infected individuals with prior lamivudine (3TC) treatment, those who switched to a didanosine (ddI)-containing regimen had a lower risk of virologic failure compared to those who continued with 3TC.

The ddI regimen remained effective against HIV strains with the M184V/I mutation, indicating that this mutation should not prevent the use of ddI in patients with prior nucleoside experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. Winters, MA., Bosch, RJ., Albrecht, MA., et al.[2022]

The updated pharmacokinetic model for octamethylcyclotetrasiloxane (D4) revealed significant discrepancies in predicting D4 concentrations in plasma and fat after long-term exposure, indicating the need for a bi-directional model to accurately reflect D4's behavior in the body.

The revised model successfully translated findings from rat studies to humans, providing accurate predictions for human inhalation and dermal exposure to D4, which is crucial for assessing safety and exposure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporation of a recirculating mobile lipid pool description into the cyclic volatile siloxane (cVMS) PBPK model captures terminal clearance of D4 after repeated inhalation exposure in F344 and SD Rats. Campbell, J., Andersen, M., Gentry, R., et al.[2023]

In the DRIVE-SHIFT trial, switching to the once-daily regimen of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained HIV-1 suppression in 80.1% of participants after 144 weeks, demonstrating long-term efficacy.

The treatment was generally well-tolerated, with low rates of virologic failure (2.1% in the immediate switch group) and no detected viral resistance, alongside improvements in fasting lipid levels and minimal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial. Kumar, P., Johnson, M., Molina, JM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06651567

A Study to Assess the Efficacy and Safety of ITI-1284 in ... A research study involving human volunteers (also called participants) that is intended to add to medical knowledge. There are two types of clinical studies: ...

2. firstwordpharma.com firstwordpharma.com/story/5232833

Intra-Cellular Therapies Announces Expansion of its ... Our recently completed Phase I program found that ITI-1284 ODT-SL was rapidly absorbed into the systemic circulation, was metabolically stable, ...

3. neurologylive.com neurologylive.com/view/intra-cellular-therapies-expands-pipeline-treat-dementia-related-psychosis

Intra-Cellular Therapies Expands Pipeline With ITI-1284 to ... A recently completed phase 1 program found that ITI-1284 ODT-SL was rapidly absorbed into the systemic circulation, was metabolically stable ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=3d84e631-13ef-4920-bf87-654358a4c962

lumateperone deuterated (ITI-1284 ODT-SL) / J&J We plan to initiate our program for the development of ITI-1284-ODT-SL for the treatment of behavioral disturbances in dementia in the second half of 2021.

5. sec.gov sec.gov/Archives/edgar/data/1567514/000119312522000753/d236940dex992.htm

EX-99.2 At a dose of 42 mg, lumateperone has been shown effective in treating the symptoms associated with schizophrenia and bipolar depression, and we believe ...

6. ctv.veeva.com ctv.veeva.com/study/a-study-to-assess-the-efficacy-and-safety-of-iti-1284-in-the-treatment-of-psychosis-associated-with-1

A Study to Assess the Efficacy and Safety of ITI-1284 in the ... 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 ...

7. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/a-2-part-study-to-investigate-lumateperone-iti-1284-in-healthy-volun/

A 2 part study to investigate Lumateperone & ITI-1284 in ... A 2 part study to investigate Lumateperone & ITI-1284 in healthy volun. Research type. Research Study. Full title. A Phase 1, Single Ascending Dose and ...