Safety, Tolerability, and Pharmacokinetics of Lumateperone in Pediatric Patients With Schizophrenia or Schizoaffective Disorder

Study Overview
=================
Brief Summary
-----------------
Study ITI-007-020 is a Phase 1b, multicenter, open-label study to evaluate the safety, tolerability, and PK of lumateperone as treatment for adolescent patients with schizophrenia or schizoaffective disorder.

Official Title
-----------------
An Open-label Multiple Oral Dose Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lumateperone in Patients, Ages 13 to 17 Years, Diagnosed With Schizophrenia or Schizoaffective Disorder

Conditions
-----------------
Pediatric, Schizophrenia

Intervention / Treatment
-----------------
* Drug: Lumateperone 42 mg
* Drug: Lumateperone 28 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Male or female patients between 13 and 17 years of age, inclusive Clinical diagnosis of schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Free from acute exacerbation of their psychosis for at least 3 months prior to Screening Clinical Global Impression - Severity (CGI-S) score ≤ 4 Body mass index (BMI) within 2 standard deviations of, age- and gender-specific body measurements (based on CDC Clinical Growth Chart, 2000) Ability to swallow capsules Main Exclusion Criteria: Has a primary psychiatric diagnosis other than schizophrenia or schizoaffective disorder Reports having experienced suicidal ideation within 6 months prior to Screening, any suicidal behavior within 2 years prior to Screening based on the Columbia-Suicide Severity Rating Scale (C-SSRS), and/or the investigator assesses the patient to be a safety risk to him/herself or others Clinically significant abnormality within 2 years of Screening that in the Investigator's opinion may place the patient at risk or interfere with study outcome variables History of a clinically significant cardiac disorder and/or abnormal screening electrocardiogram (ECG) or a QT interval corrected for heart rate using Fridericia formula > 450 msec in males or > 470 msec in females

Ages Eligible for Study
-----------------
Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lumateperone 42 mg once daily for 5 days<br> | Drug: Lumateperone 42 mg<br>* Lumateperone 42 mg, oral administration<br>|
| Experimental: Lumateperone 28 mg once daily for 5 days<br> | Drug: Lumateperone 28 mg<br>* Lumateperone 28 mg, oral administration<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Cmax | Maximum plasma concentration of lumateperone and metabolites | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 
| Pharmacokinetics: Tmax | Time of maximum concentration of lumateperone and metabolites in plasma | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 
| Pharmacokinetics: AUC0-t | Area under the plasma concentration time curve from time zero to the last measurable of concentration of lumateperone and metabolites | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 
| Pharmacokinetics: AUC0-tau | Area under the plasma concentration (lumateperone and metabolites) time curve from time zero to the end of dosing (tau) | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 
| Pharmacokinetics: t1/2 | Terminal elimination half-life of lumateperone and metabolites | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 
| Pharmacokinetics: CL/F | Apparent oral clearance of lumateperone | predose and multiple timepoints up to 24 hours postdose on Day 1 and Day 5 | 

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 20 | 
| Change from baseline in ECG QT interval |  | up to Day 6 | 
| Change from baseline in hemoglobin |  | screening, Day 6 | 
| Change from baseline in white blood cell count |  | screening, Day 6 | 
| Change from baseline in aspartate aminotransferase |  | screening, Day 6 | 
| Change from baseline in alanine aminotransferase |  | screening, Day 6 | 
| Change from baseline in Abnormal Involuntary Movement Scale (AIMS) | unabbreviated scale title: Abnormal Involuntary Movement Scale. AIMS is a measure of facial and oral movements, extremity movements and trunk movements. Items are rated on a scale from none (0) to severe (4). | up to Day 6 |