A PET Study Following a Single Oral Dose of ITI-333 in Healthy Subjects

Study Overview
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Brief Summary
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This is an open-label, single-dose study of up to 4 dose levels of ITI-333 in healthy male and female subjects. Each cohort will enroll 6 subjects. Subjects will have a baseline PET/CT scan and a postdose PET/CT scan using [14C]-MDL100907 to characterize 5-HT2A receptor occupancy

Official Title
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An Open-label, Positron Emission Tomography (PET) Study to Evaluate Brain Receptor Occupancy, Safety, Tolerability, and Pharmacokinetics After Single Oral Doses of ITI-333 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ITI-333


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects between 18 and 45 years old (inclusive); BMI inclusive of 18.0-32.0 kg/m2 at screening and a minimum weight of 50 kg; Willing to be confined to the clinical research unit for the duration of the inpatient period of the study; Exclusion Criteria: Clinically significant abnormality within 2 years of Screening that in the Investigator's opinion may place the subject at risk or interfere with study outcome variables; this includes, but is not limited to, history of or current cardiac, hepatic, renal, neurologic, gastrointestinal (including history of gastric bypass), pulmonary, endocrinologic, hematologic, or immunologic disease or history of malignancy; Clinically significant abnormal findings in vital sign assessments, including blood oxygen saturation (SpO2) < 96% and respiratory rate < 12 breaths per min; History of psychiatric condition that in the Investigator's opinion may be detrimental to participation in the study; Any condition which would preclude MRI or PET/CT examination (eg, implanted metal, claustrophobia, unable to fit in PET/CT or MRI scanners).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1: ITI-333 2.25 mg<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>|
| Experimental: Cohort A2: ITI-333 dose to be determined based on Cohort A1<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>|
| Experimental: Cohort A3: ITI-333 dose to be determined based on Cohort A1 and A2<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>|
| Experimental: Cohort A4: ITI-333 dose to be determined based on Cohort A1, A2 and A3<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: Receptor occupancy (RO) |  | baseline 90-minute PET scan between Day -5 and Day -1, and a 90-minute PET scan starting at approximately 1 hour postdose | 
| Pharmacokinetics: AUC0-t | Area under the plasma concentration time curve from time zero to the last measurable of concentration of ITI-333 and its metabolites | predose and multiple timepoints up to 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with treatment-emergent adverse events |  | up to 30 days after last dose | 
| Change from baseline in systolic and diastolic blood pressure |  | Up to Day 7 | 
| Change from baseline in ECG QT interval |  | Up to Day 7 | 
| Change from baseline in aspartate aminotransferase |  | Up to Day 7 | 
| Change from baseline in alanine aminotransferase |  | Up to Day 7 |