Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers

Study Overview
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Brief Summary
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The study will be conducted as a single-center, randomized, double-blind, placebo-controlled, ascending dose study in up to 8 sequential cohorts of healthy subjects. Each cohort will enroll 8 subjects: 6 subjects will receive ITI-333 and 2 subjects will receive placebo as a single oral dose after a fast of at least 10 hours.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ITI 333 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ITI-333
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy male and female subjects between 18 and 45 years old (inclusive); BMI inclusive of 18-32 kg/m2 at screening and a minimum weight of 50 kg; Willingness to remain in the clinic for the inpatient portion of the study and return for follow-up visit(s) as required by protocol and as deemed necessary by the Investigator; Key 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, GI, pulmonary, endocrinologic, hematologic, or immunologic disease or history of malignancy; Clinically significant abnormal findings in vital sign assessments, including blood oxygen saturation (SAO2) < 96% and < 12 breaths per min; History of psychiatric condition that in the Investigator's opinion may be detrimental to participation in the study

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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential ascending doses. Parallel (active, placebo) within each cohort
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 0.03 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 2: 0.09 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 3: 0.25 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 4: 0.75 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 5: 2.25 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|
| Experimental: Cohort 6: 6.75 mg ITI-333 or placebo<br> | Drug: ITI-333<br>* ITI-333 oral solution<br>Other: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary 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 12 | 
| Change from baseline in SAO2 |  | Up to Day 12 | 
| Change from baseline in ECG QT interval |  | Up to Day 12 | 
| Change from baseline in hemoglobin |  | Up to Day 12 | 
| Change from baseline in white blood cell count |  | Up to Day 12 | 
| Change from baseline in aspartate aminotransferase |  | Up to Day 12 | 
| Change from baseline in alanine aminotransferase |  | Up to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: AUC0-t | Area under the plasma concentration time curve from time zero to the last measurable of concentration of ITI-333 and metabolites | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: AUC0-inf | Area under the plasma concentration (ITI-333 and metabolites) time curve from time zero to infinity | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: Cmax | Maximum plasma concentration of ITI-333 and metabolites | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: Tmax | Time of maximum concentration of ITI-333 and metabolites in plasma | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: T1/2 | Terminal elimination half-life of ITI-333 and metabolites | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: CL/F | Apparent oral clearance of ITI-333 | predose and multiple timepoints up to 96 hours postdose | 
| Pharmacokinetics: Vz/F | Apparent volume of distribution of ITI-333 | predose and multiple timepoints up to 96 hours postdose |