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

Trial Summary

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.

What makes the drug ITI-1284 unique compared to other treatments?

ITI-1284, also known as deuterated lumateperone, is unique because it is a modified version of lumateperone with deuterium, which may enhance its stability and effectiveness. This drug is administered as an orally disintegrating tablet that dissolves under the tongue, offering a potentially more convenient and faster-acting option compared to traditional oral medications. ^{1 2 3 4 5}

What is the purpose of this trial?

The study will be conducted as an open-label and single-center study to evaluate the occupancy of ITI-1284 to the dopamine D2 receptor, serotonin 2A (5-HT2A) receptor, and serotonin transporter (SERT) in healthy subjects.

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. United States 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. [2023]

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

Nevirapine/didanosine/lamivudine once daily in HIV-1-infected intravenous drug users. [2013]

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

Presence of M184I/V in minor HIV-1 populations of patients with lamivudine and/or didanosine treatment failure. [2013]

4. Netherlands 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. [2023]

5. United States 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. [2022]