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
Phase: PHASE1
Conditions: Schizophrenia, Pediatric
Sponsor: Intra-Cellular Therapies, Inc.

 
NCT04779177 
 
Study ID: ITI-007-020 
 
Title: An Open-label Multiple Dose Study to Determine the Pharmacokinetics, 
Safety, and Tolerability of Lumateperone in Patients, Ages 13 to 17 Years, 
Diagnosed with Schizophrenia or Schizoaffective Disorder 
 
 
 
 
 
 
 
Protocol Amendment Version 5.0 Date: February 28, 2022 
 

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TITLE PAGE 
An Open-label Multiple Dose Study to Determine the Pharmacokinetics, Safety, and 
Tolerability of Lumateperone in Patients, Ages 13 to 17 Years, Diagnosed with 
Schizophrenia or Schizoaffective Disorder 
Protocol Number: 
ITI-007-020 
 
 
 
 
 
 
 
 
 
 
Compound: 
Lumateperone 
Study Phase: 
1b 
Sponsor: 
Intra-Cellular Therapies, Inc. 
 
 
 
IND 
079690 
Confidentiality Statement 
The confidential information in this document is provided to you as an Investigator for review by you, your 
staff, and the applicable Institutional Review Board. Acceptance of this document constitutes agreement that 
the information contained herein will not be disclosed to others without written authorization from the 
Sponsor. All financial and nonfinancial support for this study will be provided by Intra-Cellular Therapies, 
Inc. (ITI or ITCI). The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the expressed, written consent 
of ITCI. 
This study will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice, US Code of Federal Regulations applicable to clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 
CFR Part 56, 21 CFR Part 312), and all applicable local regulations.

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PROTOCOL VERSION 5: MAJOR CHANGES 
Protocol Version 5 for Study ITI-007-020, dated 28 Feb 2022, provides revisions and clarifications 
to the Protocol Version 4.0 (dated 14 Dec 2021; see Appendix II for the Summary of Changes for 
Protocol Version 4.0). Major changes to the protocol are summarized in the table below.  
New text is bold and italicized; deleted text is displayed as strikethroughs. Editorial corrections 
and minor revisions for consistent terminology usage are not summarized in this table. 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
t 

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Protocol Section 
Revision  
Rationale 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Section 
Revision  
Rationale 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 

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TABLE OF CONTENTS 
PROTOCOL VERSION 5: MAJOR CHANGES........................................................................... 2 
TABLE OF CONTENTS ................................................................................................................ 5 
LIST OF ABBREVIATIONS ......................................................................................................... 9 
1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF EVALUATIONS ................................ 11 
2. 
ETHICAL CONSIDERATIONS ....................................................................................... 18 
2.1 
Institutional Review Board............................................................................................. 18 
2.2 
Ethical Conduct of the Study ......................................................................................... 18 
2.3 
Patient Information and Informed Consent .................................................................... 18 
3. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ......................... 19 
4. 
INTRODUCTION .............................................................................................................. 20 
5. 
STUDY OBJECTIVES ...................................................................................................... 22 
6. 
INVESTIGATIONAL PLAN ............................................................................................ 23 
6.1 
Overall Study Design and Plan ...................................................................................... 23 
6.2 
Scientific Rationale for Study Design ............................................................................ 23 
6.2.1 
Study Design............................................................................................................... 23 
6.2.2 
Dose Selection ............................................................................................................ 23 
6.3 
Study Population ............................................................................................................ 24 
6.3.1 
Inclusion Criteria ........................................................................................................ 24 
6.3.2 
Exclusion Criteria ....................................................................................................... 25 
6.4 
Discontinuation of Patients from Therapy or Assessments ........................................... 26 
6.5 
Patient Replacement Procedures .................................................................................... 27 
6.6 
Changes in the Conduct of the Study ............................................................................. 27 
7. 
STUDY TREATMENT ..................................................................................................... 28 
7.1 
Treatment Administered ................................................................................................. 28 
7.2 
Preparation, Handling, Storage, and Accountability of Study Drug .............................. 28 
7.2.1 
Storage of Study Drug ................................................................................................ 28 
7.2.2 
Study Treatment Accountability ................................................................................. 29 
7.3 
Method of Assigning Patients to Treatment Groups ...................................................... 29 
7.4 
Blinding .......................................................................................................................... 29 
7.5 
Unblinding ...................................................................................................................... 29 
7.6 
Monitoring Treatment Compliance ................................................................................ 29 
7.7 
Prior and Concomitant Medications ............................................................................... 29 

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7.7.1 
Prior Medications ....................................................................................................... 29 
7.7.2 
Concomitant Medications ........................................................................................... 30 
7.8 
Washout of Antipsychotic and Anti-anxiety Medications ............................................. 30 
7.9 
Special Diet or Activities ............................................................................................... 30 
7.9.1 
Dietary Restrictions .................................................................................................... 30 
7.9.2 
Alcohol and Tobacco .................................................................................................. 31 
7.9.3 
Activity ....................................................................................................................... 31 
7.10 
Treatment After Discontinuation ................................................................................... 31 
8. 
SAFETY, PHARMACOKINETIC, AND OTHER ASSESSMENTS .............................. 32 
8.1 
Safety .............................................................................................................................. 32 
8.1.1 
Adverse Events ........................................................................................................... 32 
8.1.2 
Potential Hy’s Law Cases ........................................................................................... 36 
8.1.3 
Pregnancy ................................................................................................................... 36 
8.1.4 
Clinical Laboratory Determinations ........................................................................... 37 
8.1.5 
Vital Signs .................................................................................................................. 38 
8.1.6 
Electrocardiograms ..................................................................................................... 39 
8.1.7 
Other Safety Assessments .......................................................................................... 39 
8.2 
Pharmacokinetic Assessments........................................................................................ 41 
8.3 
Blood Volume ................................................................................................................ 41 
 
 
9. 
STATISTICAL METHODS .............................................................................................. 47 
9.1 
General Considerations .................................................................................................. 47 
9.2 
Determination of Sample Size........................................................................................ 47 
9.3 
Analysis Populations ...................................................................................................... 47 
9.4 
Patient Disposition ......................................................................................................... 47 
9.4.1 
Demographics and Other Baseline Characteristics .................................................... 47 
9.4.2 
Extent of Exposure and Treatment Compliance ......................................................... 48 
9.4.3 
Extent of Exposure ..................................................................................................... 48 
9.4.4 
Prior and Concomitant Medication ............................................................................. 48 
9.5 
Efficacy Analyses ........................................................................................................... 48 
9.6 
Safety Analyses .............................................................................................................. 48 
9.6.1 
Adverse Events ........................................................................................................... 48 

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9.6.2 
Clinical Laboratory Parameters .................................................................................. 49 
9.6.3 
Vital Signs .................................................................................................................. 49 
9.6.4 
Electrocardiogram ...................................................................................................... 49 
9.6.5 
Other Safety Parameters ............................................................................................. 50 
9.7 
Plasma Concentration Parameters .................................................................................. 50 
9.8 
Interim Analysis ............................................................................................................. 51 
9.9 
Protocol Deviations ........................................................................................................ 51 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL MONITORING .............. 52 
10.1 
Study Termination .......................................................................................................... 52 
10.2 
Investigator Obligations ................................................................................................. 52 
10.2.1 
Documentation ........................................................................................................ 52 
10.2.2 
Performance ............................................................................................................ 52 
10.2.3 
Use of Investigational Materials ............................................................................. 52 
10.2.4 
Case Report Forms .................................................................................................. 53 
10.2.5 
Retention and Review of Records........................................................................... 53 
10.2.6 
Patient Confidentiality ............................................................................................ 53 
10.3 
Data Quality Assurance .................................................................................................. 54 
10.3.1 
Data Monitoring ...................................................................................................... 54 
10.3.2 
Data Recording and Documentation ....................................................................... 54 
10.4 
Reporting and Publication .............................................................................................. 55 
11. 
REFERENCES ................................................................................................................... 56 
12. 
APPENDICES .................................................................................................................... 57 
Appendix I. 
Elements of Informed Consent ........................................................................ 57 
Appendix II. 
Protocol Version 4.0–Summary of Changes ................................................... 58 
13. 
INVESTIGATOR SIGNATURE PAGE ............................................................................ 61 

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LIST OF TABLES 
Table 1-1: Schedule of Evaluations .............................................................................................. 15 
Table 7-1: Lumateperone Capsules .............................................................................................. 28 
Table 8-2: Blood Volumes (mL) to Be Collected ......................................................................... 41 
 

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LIST OF ABBREVIATIONS 
AE 
adverse event 
AIMS 
Abnormal Involuntary Movement Scale 
ALT 
alanine aminotransferase  
aPTT 
partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
Area under the plasma concentration time curve 
AUC0-24 
Area under the plasma concentration time curve from time zero to 
24 hours 
AUC0-t 
Area under the plasma concentration time curve from time zero to 
the last measurable concentration 
AUC0-inf 
Area under the plasma concentration time curve from time zero to 
infinity 
 
 
BMI 
body mass index 
BP 
blood pressure 
CFR 
Code of Federal Regulations 
 
 
CGI-S 
Clinical Global Impression Scale-Severity 
CL/F 
Apparent oral clearance 
Cmax 
Maximum plasma drug concentration 
CRU 
Clinical research unit 
ECG 
electrocardiogram, electrocardiographic 
eCRF 
electronic case report form 
EDC 
electronic data capture 
ET 
early termination 
FDA 
Food and Drug Administration 
FR 
Federal Register 
λz 
Terminal elimination rate constant 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 

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ICH 
International Council on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use 
IND 
Investigational New Drug (application) 
IRB 
Institutional Review Board 
LAR 
Legally authorized representative 
PT 
prothrombin time 
QTcB 
QT interval corrected for heart rate using the Bazett formula  
QTcF 
QT interval corrected for heart rate using the Fridericia formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
 
 
SOC 
System organ class 
t 1/2 
Terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
Tmax 
Time of maximum concentration of drug in plasma  
ULN 
upper limit of normal 
VZ/F 
Apparent volume of distribution 

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1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF EVALUATIONS 
CLINICAL STUDY SYNOPSIS: Study ITI-007-020 
Title of Study 
An Open-label, Multiple Dose Study to Determine the Pharmacokinetics, 
Safety, and Tolerability, of Lumateperone in Patients, Ages 13 to 17 Years, 
Diagnosed with Schizophrenia 
Study Centers (Country) 
Approximately 3 study centers in the United States. 
Development Phase 
Phase 1b 
Objectives 
• To determine the pharmacokinetic (PK) profile of lumateperone at 
steady state following once daily oral administration for 5 days in 
adolescent patients, aged 13 to 17 years; 
• To assess the safety and tolerability of lumateperone following oral 
administration for 5 days in adolescent patients, ages 13 to 17 years. 
Methodology 
This is a multiple-dose, open-label study of oral lumateperone in patients, 
aged 13 to 17 years, diagnosed with schizophrenia. 
CAPLYTA® (lumateperone 42 mg) is approved in the United States for the 
treatment for schizophrenia in adults. The purpose of this study is to evaluate 
the PK safety, and tolerability of oral lumateperone in adolescent patients, 
aged 13 to 17 years. 
Adolescent patients with schizophrenia or schizoaffective disorder may be 
screened for eligibility (Day -14 to Day -1). Patients who are currently 
receiving antipsychotic treatment must wash off current medication with 
Investigator supervision. 
Eligible patients will be admitted to an inpatient clinical research unit (CRU) 
on Day -1. A thorough baseline assessment will be conducted prior to the 
first dose of lumateperone on Day 1. Oral lumateperone will be administered 
under fasted conditions, once daily in the morning for 5 days (Days 1 to 5). 
After the final post-dose assessments are conducted on Day 6, patients 
considered to be stabilized may be discharged from the inpatient CRU on 
Day 6. Patients requiring additional time for stabilization may remain in the 
CRU up to Day 10.  
Patients aged 13 to 17 years will receive lumateperone 42 mg. 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 

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Blood samples for PK analysis following oral lumateperone administration 
will be collected on Days 1 and 5 
 
 
 
 
 
 
Time of study drug administration and time of collection of each blood 
sample must be recorded. 
Safety and tolerability will be assessed throughout the study. 
Number of Patients 
Approximately 18 to 24 patients are planned.  
Diagnosis and Main Inclusion and 
Exclusion Criteria  
Main Inclusion Criteria:  
A patient will be considered eligible for participation in the trial if the 
following inclusion criteria are satisfied at the Screening Visit and upon 
admission to the CRU (Day -1): 
1. Able to provide consent as follows: 
• 
Legally authorized representative of the patient must provide 
written, informed consent; 
• 
Patient must assent to study enrollment 
2. Male or female patients between 13 and 17 years of age, inclusive, 
at Screening;  
3. Clinical diagnosis of schizophrenia or schizoaffective disorder 
according to Diagnostic and Statistical Manual of Mental 
Disorders, Fifth Edition (DSM-5); 
4. Free from acute exacerbation of psychosis for at least 3 months 
prior to Screening; 
5. CGI-S score ≤ 4; 
8. Ability to swallow capsules; and 
9. Willing to be confined to an inpatient unit for the duration of the 
inpatient period of the study, and, in the opinion of the Investigator, 
willing to comply with all Investigator and staff instructions. 
All Inclusion Criteria are presented in Section 6.3.1. 
 
Main Exclusion Criteria: 
A patient presenting with any of the following characteristics will be 
excluded from the study: 
1. Has a primary psychiatric diagnosis other than schizophrenia or 
schizoaffective disorder; 
2. Reports having experienced suicidal ideation (Type 4 or 5 on the 
Baseline/Screening version of the Columbia-Suicide Severity 
Rating Scale [C-SSRS]) within 6 months prior to Screening, any 
suicidal behavior within 2 years prior to Screening (any “Yes” 
answers on Suicidal Behavior section of C-SSRS), and/or the 
investigator assesses the patient to be a safety risk to him/herself or 
others; 
3. 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; 

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4. 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; this includes, but is not 
limited to, history or clinical presentation of a neurodevelopmental 
disorder or history of other clinically significant neurologic, 
hepatic, renal, gastrointestinal, respiratory, hematologic, endocrine 
or immunologic disease or history of malignancy. 
All Exclusion Criteria are presented in Section 6.3.2. 
Test Product, Dosage, and Mode of 
Administration 
Lumateperone 42 mg; lumateperone 28 mg 
Once daily oral administration. 
Duration of Treatment 
5 days  
Reference Therapy, Dosage, and Mode 
of Administration 
Not applicable. 
Criteria for Evaluation 
Pharmacokinetic Endpoints 
The following PK Parameters will be calculated for Days 1 and 5 for 
lumateperone 
 
• Time of maximum concentration of drug in plasma (Tmax) 
• Maximum plasma drug concentration (Cmax)  
• Whenever possible, relative ratios of metabolite to parent will be 
calculated 
• Area under the plasma concentration time curve (AUC) from time 
zero to the last measurable concentration (AUC0-t) 
• AUC from time zero to the end of the dosing interval, tau (AUC0-tau) 
• Area under the plasma concentration time curve (AUC) from time 
zero to infinity (AUC0-inf) - only for Day 1, as data permit 
• Terminal elimination rate constant (λz) 
• Terminal elimination half-life (t½) 
• Apparent oral clearance (CL/F)
 
• Apparent volume of distribution (VZ/F) 
. 
Safety Measures 
Safety will be assessed by: 
• Adverse event (AE) recording, clinical laboratory parameters 
(hematology, serum chemistry and urinalysis), vital sign parameters 
(blood pressure and heart rate, respiration rate, body temperature, 
weight, height, and BMI), 12-lead ECGs, and physical examinations, 
including neurological findings, pregnancy test, concomitant 
medications 
• 
 
• 
 
 Abnormal Involuntary 
Movement Scale (AIMS) 
• Measure of suicidality: C-SSRS 
Statistical Methods 
Detailed statistical methods will be described in a separate statistical 
analysis plan. 
Analysis Sets: 
Enrolled Set: Includes all patients who signed the informed consent form 
(ICF) and will be used to describe patient disposition. 
Safety Set: Includes all patients who receive at least one dose of study drug. 
PK Set: Includes all patients who received at least one dose of study drug, 

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had no major protocol deviation that may impact PK analyses, and had at 
least one evaluable PK parameter. Patients who experience emesis within 
2 times the median Tmax after receiving an oral dose may be excluded from 
the PK analysis. 
Pharmacokinetic Analysis 
Plasma concentrations of lumateperone
 
 
 
 
Analyses will be performed for parent drug
 using non-
compartmental methods. 
Individual plasma concentrations will be presented in data listings. Plasma 
concentration data will be summarized over time (and by dose, if applicable) 
using descriptive statistics. Mean and individual plasma concentration vs 
time profiles will be presented in figures on both linear and semi-logarithmic 
scales. The individual PK parameters will be presented in data listings and 
summarized using descriptive statistics. Geometric means will be included 
for Cmax, AUC0-t, AUC0-inf, AUC0-tau, CL/F, and VZ/F. 
 
 
The PK data may be included in a population PK analysis pooled with adult 
patient data. The results from the population PK analysis will be reported in 
a separate report. 
Safety Analysis 
All safety data (AEs, safety laboratory results, vital sign measurements, 
12-lead ECG results, physical examinations, 
, AIMS, 
 will be presented in the data listings. Adverse events will be 
summarized overall (and by dose if more than one dose is administered) for 
patients in the Safety Set. Adverse events will also be summarized by 
severity, relationship to study drug, serious AEs, and AEs leading to 
discontinuation from the study.  
Patient disposition, demographics, and baseline characteristics will be 
summarized overall (and by dose if more than one dose is administered) for 
patients in the Safety Set. Baseline values, postbaseline values, and changes 
from baseline of safety laboratory results, vital sign measurements, 12-lead 
ECG, 
 AIMS results will be summarized overall 
(and by dose if more than one dose is administered) at each time point using 
descriptive statistics. 
 
 
 
Sample Size 
 
 
  
 
 
 
 
 

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2. 
ETHICAL CONSIDERATIONS 
2.1 
Institutional Review Board 
Approval by the Institutional Review Board (IRB) before the start of the study will be the 
responsibility of the Investigator. A copy of the approval letter will be supplied to Intra-Cellular 
Therapies, Inc. (the Sponsor) or its designee along with a roster of IRB members. During the course 
of the study, the Investigator will provide timely and accurate reports to the IRB on the progress 
of the study, at intervals not exceeding 1 year (or as appropriate) and will notify the IRB of serious 
adverse events (SAEs) or other significant safety findings. The study protocol, informed consent 
form (ICF), age-appropriate assent form, information sheet advertisements, and amendments (if 
any) will be approved by the IRBs at the study centers in conformance with US CFR, Title 21, 
Part 56. 
2.2 
Ethical Conduct of the Study 
This clinical study will be conducted in accordance with the ethical principles that have their 
origins in the Declaration of Helsinki. This clinical study will comply with the ICH Guidance on 
General Considerations for Clinical Trials (ICH-E8; 62 FR 66113, 17 Dec 1997) and GCP (ICH-
E6; 62 FR 25692, March 2018), as well as CFR Part 312. 
2.3 
Patient Information and Informed Consent 
A written informed consent in compliance with US Title 21 Code of Federal Regulations (CFR) 
Part 50 and 21 CFR Part 50, Subpart D shall be obtained from the legally authorized representative 
(LAR) in accordance with local laws or regulations and before entering the study or performing 
any study-specific procedure that involves risk to the patient. Adolescent patients should be 
informed to the fullest extent possible about the study in language and terms they are able to 
understand. Patients should provide written assent by signing the assent form or the ICF. Patients 
who reach the age of consent or become an emancipated minor while participating in the study 
will be required to provide written consent. In all cases, patients and their LARs should be made 
aware of their rights to decline to participate or to withdraw from the study at any time. 
If the ICF is revised during the study, all active participating patients must assent and their LARs 
must sign the revised form. The informed consent statement shall contain all the elements of 
informed consent listed in Appendix I. 
Before any screening procedures, each prospective patient will be given a full explanation of the 
study. After receiving an explanation of study procedures, patients and their LARs will have the 
opportunity to have any questions answered before signing the ICF. The Investigator must address 
all questions raised by the patient. Attention should be paid to signs of undue distress in adolescent 
patients who are unable to clearly articulate their distress. 
The Investigator or designee will also sign the ICF and provide copies of the ICF and the HIPAA 
(Health Insurance Portability and Accountability Act) or other locally applicable form to the 
patient and their LAR. The Investigator shall retain the signed original ICF, assent, and HIPAA 
form. 

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3. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
Contact information for the clinical vendors responsible for study conduct and a list of Sponsor 
study contacts are provided in the Study Reference Manual. 
 

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4. 
INTRODUCTION 
Schizophrenia is a severe brain disorder that affects 1% to 2% of the world’s population. This 
chronic and disabling disorder is characterized by “positive” symptoms such as hallucinations and 
delusions, “negative” symptoms such as flattened affect and social withdrawal, and cognitive 
deficits. According to the National Institute of Mental Health (NIMH), symptoms of schizophrenia 
usually emerge in people aged 16 to 30 years, but schizophrenia in teens can be difficult to 
diagnose because the first signs might include irritability, depressed mood, social difficulties, and 
a drop in grades. These clinical signs are common in teens and may not necessarily correspond to 
the emergence of schizophrenia. A combination of these factors together with symptoms such as 
increasing paranoia and suspiciousness, increased social withdrawal, and a family history of 
psychosis contribute to the “prodromal” period that occurs prior to the onset/diagnosis of 
schizophrenia. 
Childhood-onset schizophrenia, before the age of 13, is very rare with an incidence of less than 
0.04% (Driver et al, 2013), and accurate diagnosis is very challenging with a drug-free inpatient 
observation period proving more helpful than outpatient assessments for differential diagnosis 
(Gochman et al, 2011). Limited and transient psychotic symptoms are common in many childhood 
disorders and even among healthy children, which contributes to the difficulty with differential 
diagnosis. Onset of schizophrenia during the mid and late teens is more common, and an estimated 
12% to 33% of adults with schizophrenia may have first symptoms and signs of schizophrenia 
before age 18 (Kumra et al, 2008). Adult diagnostic criteria and assessment measures can be used 
successfully in an unmodified manner for adolescent schizophrenia (Hollis, 2000). Hollis also 
summarized the clinical features of schizophrenia and treatment in adolescent schizophrenia. 
Clinical features of schizophrenia in adolescents include poor premorbid functioning, cognitive 
dysfunction indicated by below average IQ, and prominent negative symptoms. Adolescent 
patients with schizophrenia often have a family history of psychosis and/or schizophrenia. The 
disorder generally has a slow onset with gradual presentation of behavioral disturbances but 
follows a severe course that is difficult to treat in this young patient population. Sadly, adolescent 
schizophrenia has been associated with extremely poor social outcomes. Currently available 
antipsychotics approved for the treatment of schizophrenia in adolescents include risperidone, 
aripiprazole, quetiapine, and paliperidone, and lurasidone. Although antipsychotic treatment has 
been shown to reduce positive psychotic symptoms in adolescents, currently available treatments 
insufficiently improve negative symptoms or social functioning and are associated with adverse 
events such as motor and cognitive impairment, weight gain and dyslipidemia, and 
hyperprolactinemia. Olanzapine is approved for use in adolescents with schizophrenia, but its label 
recommends it only as a second-line treatment given its propensity to cause weight gain and 
hyperlipidemia. Notably, children and adolescents have been observed to be more sensitive to 
antipsychotic adverse effects than adults (Correll, 2008). 
CAPLYTA® (lumateperone 42 mg oral capsule) was approved for the treatment of schizophrenia 
in adults in the United States in December 2019. The efficacy of CAPLYTA 42 mg was 
demonstrated in two placebo-controlled trials, showing a statistically significant separation from 
placebo on the primary endpoint, the Positive and Negative Syndrome Scale (PANSS) total score. 
The most common adverse reactions in adults (≥ 5% and twice the rate of placebo) for the 
recommended dose of CAPLYTA vs placebo were somnolence/sedation (24% vs. 10%) and dry 
mouth (6% vs. 2%). In pooled data from short-term studies, mean changes from baseline in weight 

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gain, fasting glucose, triglycerides and total cholesterol were similar between CAPLYTA and 
placebo. The incidence of extrapyramidal symptoms was 6.7% for CAPLYTA and 6.3% for 
placebo. 
Pursuant to the FDA postmarketing requirement for CAPLYTA (PMR 3760-1), this study will be 
an open-label, multiple-dose study to demonstrate the safety, tolerability, and pharmacokinetics 
(PK) of lumateperone in patients aged 13 to 17 years diagnosed with schizophrenia or 
schizoaffective disorder. 

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5. 
STUDY OBJECTIVES 
The objectives of this study are: 
• To determine the PK profile of lumateperone at steady state following once daily oral 
administration for 5 days in adolescent patients aged 13 to 17 years 
• To assess the safety and tolerability of lumateperone following oral administration for 
5 days in adolescent patients aged 13 to 17 years. 

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6. 
INVESTIGATIONAL PLAN 
6.1 
Overall Study Design and Plan 
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. This study will be performed at approximately 3 study centers in the United States. 
The study will be conducted as follows: 
• A Screening Period of up to 14 days: Adolescent patients with stable schizophrenia or 
schizoaffective disorder maintained on not more than one oral antipsychotic for the treatment 
of schizophrenia (ie, can be stable without antipsychotic medications or stable on a single 
antipsychotic) may be screened for eligibility (Day -14 to Day -1). The washout of current 
antipsychotic medication and anti-anxiety medications (except lorazepam) will be carried out 
for a period of 4 to 7 days prior to Day 1 and may be implemented on an inpatient basis during 
the Screening Period based on the Investigator’s clinical judgment. An extension to the 
Screening Period and/or washout may be allowed with the approval of the Sponsor. 
• A 5-day Open-label Treatment Period: Oral lumateperone will be administered under fasted 
conditions, once daily in the morning for 5 days (Days 1 to 5). 
• An up to 5-day Standard-of-Care Stabilization Period: After the final post-dose assessments 
are conducted on Day 6, patients will be returned to standard-of-care antipsychotic treatment. 
If, in the opinion of the Investigator, a patient is considered to be stable he/she may be 
discharged after completion of all Day 6 assessments. If, in the opinion of the Investigator, 
patients require additional time for stabilization, they may remain in the CRU between Days 7 
and 10. Additional days for stabilization may be approved by the Sponsor. 
• A Follow-up Visit will be conducted approximately 14 days after the last dose of study drug. 
The maximum per-patient study duration will be approximately 5 weeks. 
The Schedule of Evaluations is presented in Table 1-1. Detailed descriptions of the procedures 
conducted at each study visit are provided in Section 8.3. 
6.2 
Scientific Rationale for Study Design 
6.2.1 Study Design 
The study is designed to determine the PK profile of lumateperone in adolescent patients with 
schizophrenia. 
6.2.2 Dose Selection 
Patients aged 13 to 17 years will receive lumateperone 42 mg/day. 
 
 
 

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6.3 
Study Population 
Patients must meet all inclusion criteria and none of the exclusion criteria in order to be eligible to 
participate in the study. Patients who do not meet the criteria for participation in the study may be 
re-screened upon approval by the Sponsor. 
6.3.1 Inclusion Criteria 
A patient will be considered eligible for participation in the trial if the following inclusion criteria 
are satisfied at the Screening Visit (Visit 1) and upon admission (Day -1): 
1. Able to provide consent as follows: 
• 
Legally authorized representative of the patient must provide written, informed 
consent; 
• 
Patient must assent to study enrollment; 
2. Male or female patients between 13 and 17 years of age, inclusive, at the time of providing 
informed consent;  
3. Clinical diagnosis of schizophrenia or schizoaffective disorder according to Diagnostic and 
Statistical Manual of Mental Disorders, Fifth Edition (DSM-5); 
4. Free from acute exacerbation of their psychosis for at least 3 months prior to Screening; 
5. Clinical Global Impression – Severity (CGI-S) score ≤ 4; 
6. Female patients of childbearing potential must have a negative serum pregnancy test at the 
Screening Visit (Visit 1) and a negative urine pregnancy test on Day -1 (upon admission to 
the CRU) and  
• 
Agree to remain abstinent, or 
• 
Agree to practice double barrier forms of birth control in which 2 of the following 
precautions are used: vaginal diaphragm, intrauterine device, oral contraceptive pills 
or injectable, birth control implant, or condom or sponge with spermicide from 
Screening through to completion of the study or upon early termination; 
• 
Not be breastfeeding. 
7. Body mass index (BMI) equal to or within the 5th and 95th percentiles according to age- 
and gender-specific CDC Clinical Growth Charts, 2000 at Screening; 

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8. Ability to swallow capsules, and 
9. Willing to be confined to an inpatient unit for the duration of the inpatient period of the 
study, and, in the opinion of the Investigator, willing to comply with all Investigator and 
staff instructions. 
6.3.2 Exclusion Criteria 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the 
study: 
1. Has a primary psychiatric diagnosis other than schizophrenia or schizoaffective disorder; 
2. Reports having experienced suicidal ideation (Type 4 or 5 on the Baseline/Screening 
version of the Columbia-Suicide Severity Rating Scale [C-SSRS]) within 6 months prior 
to Screening, any suicidal behavior within 2 years prior to Screening (any “Yes” answers 
on Suicidal Behavior section of C-SSRS), and/or the investigator assesses the patient to be 
a safety risk to him/herself or others; 
3. 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; 
4. 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; this 
includes, but is not limited to, history or clinical presentation of a neurodevelopmental 
disorder or history of other clinically significant neurologic, hepatic, renal, gastrointestinal, 
respiratory, hematologic, endocrine or immunologic disease or history of malignancy; 
5. Surgical or medical condition (active or chronic) that in the Investigator’s opinion may 
interfere with drug absorption, distribution, metabolism, or excretion of the study drug or 
any other condition that may place the patient at risk;  
6. Meets Diagnostic and Statistical Manual of Mental Disorders (5th Edition) criteria for 
substance use disorder within 6 months before Screening; 
7. Positive result for drugs of abuse, alcohol, or cotinine at Screening or Day -1. The drug 
screen may be repeated once based on Investigator judgement as approved by the Sponsor; 
8. Major surgery or blood loss within 4 months prior to Day -1; 
9. History of clinically significant drug allergy or sensitivity, including a known sensitivity 
or idiosyncratic reaction to lumateperone or drugs of the same class, any metabolites, or 
any compound listed in the study formulation; 
10. Clinically significant abnormal findings in serum chemistry, coagulation, hematology, or 
urinalysis results obtained at Screening; 
11. History of human immunodeficiency virus (HIV) infection; 
12. History of hepatitis B or hepatitis C infection or demonstration of hepatitis B surface 
antigens or hepatitis C antibodies; 

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13. Has had exposure to any investigational product within 90 days or 5 half-lives (whichever 
is longer) prior to Day -1; 
14. Ingested any medication or herbal supplements (excluding hormonal birth control, 
documented current antipsychotic therapy, documented current anti-anxiety medications, 
lorazepam, or multivitamins) within 5 half-lives or 14 days (whichever is longer) prior to 
Day -1; 
15. In the opinion of the Investigator, the patient is unable to safely undergo washout of 
antipsychotic treatment (excluding depot antipsychotic) for a period of 4 to 7 days prior to 
Day 1. 
16. Use of depot antipsychotic within 3 treatment cycles prior to Day -1; 
17. Patients cannot be treatment-naïve, must not be on > 1 antipsychotic at the Screening Visit, 
or have ever taken clozapine; 
18. Consumed grapefruit-, alcohol-, or xanthine-containing products within 24 hours before 
receipt of study drug on Day 1; 
19. Is a current tobacco or nicotine user;  
20. Has participated in strenuous activity or contact sports within 24 hours before study drug 
dosing on Day 1;  
21. In the opinion of the Investigator, the patient is not otherwise suitable for entry into the 
study. 
6.4 
Discontinuation of Patients from Therapy or Assessments 
A premature discontinuation will occur when a patient who received a dose of study drug ceases 
participation in the study, regardless of circumstances, before the completion of study visits and 
procedures through Day 6. Patients can be prematurely discontinued from the study after careful 
consideration for one of the following reasons: 
• Death 
• AE 
• Lost to follow-up 
• Pregnancy 
• Physician decision 
• Protocol violation 
• Study terminated by Sponsor 
• Withdrawal by subject 
• Withdrawal by parent/guardian/LAR 
• Other. 

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NOTE: If a patient discontinues from the study due to withdrawal of assent or due to withdrawal 
of parent/guardian/LAR consent and a concurrent AE was reported, the study site should query 
and confirm the primary reason for discontinuation and record the primary reason for 
discontinuation on the electronic case report form (eCRF). 
Patients who are lost to follow-up and do not return to the study center for the Follow-up Visit 
must be requested in writing to return to the study center for a final assessment. A copy of the 
letter, together with the source documentation, will be kept in the Investigator’s files. The reason 
for premature discontinuation from the study will be recorded on the Study Termination Page of 
the eCRF. Study center staff may be contacted by the Sponsor after each premature discontinuation 
to ensure that proper characterization of the reason for discontinuation is captured. 
All patients who prematurely discontinue from the study regardless of cause should be seen for a 
final assessment at the early termination (ET) Visit (Visit 8). All patients who prematurely 
discontinue from the study should return for the safety follow-up visit. 
6.5 
Patient Replacement Procedures 
Patients who prematurely discontinue from the study during the Open-label Treatment Period may 
be replaced. 
6.6 
Changes in the Conduct of the Study 
Any amendment to this protocol will be provided by the Sponsor in writing to the Investigator. No 
protocol amendment may be implemented before it has been approved by the IRB and the signature 
page, signed by the Investigator, has been received by the Sponsor. An amendment may be 
implemented by Investigator based only on patient safety concerns. However, the Sponsor must 
be informed of such change immediately. The IRB must be informed in writing of such an 
amendment; IRB approval must be obtained within reasonable time limits. 

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7. 
STUDY TREATMENT 
7.1 
Treatment Administered 
Open-label lumateperone will be administered only to eligible patients under the supervision of 
the Investigator or sub-investigators or other designated personnel authorized to administer 
treatment. Open-label lumateperone will be administered orally once daily for 5 days, from Day 1 
through Day 5. Study drug should be administered at the same time each day ± 15 minutes. Study 
drug will be administered with about 240 mL of water. On Days 1 and 5, lumateperone will be 
administered following an overnight fast of at least 10 hours; fasting will continue for at least 
4 hours postdose. On Days 2-4, lumateperone will be administered after an overnight fast of at 
least 8 hours; this fast will continue for at least 2 hours post dose. Water can be provided as desired 
except for 1 hour before and 1 hour after dosing. 
Open-label lumateperone will be supplied as capsules provided in 2×5 blister cards. Table 7-1 
provides formulation information for lumateperone. 
Study drug will be labeled according to local laws and regulations.  
 
 
Table 7-1: Lumateperone Capsules 
 
Lumateperone 42 mg 
Lumateperone 28 mg 
Frequency 
Once daily 
Once daily 
Route 
Oral 
Oral 
Formulation 
Capsule 
Capsule 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7.2 
Preparation, Handling, Storage, and Accountability of Study Drug 
7.2.1 Storage of Study Drug  
Study drug must be stored in a secure area (eg, a locked cabinet) while in storage at the study site, 
protected from moisture, and kept at a room temperature between 15°C and 30°C (59°F-86°F).  

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7.2.2 Study Treatment Accountability 
The Investigator will maintain accurate records of receipt of all study drug, including dates of 
receipt. In addition, accurate records will be kept regarding when and how much study drug is 
dispensed and used by each patient in the study. To satisfy regulatory requirements regarding drug 
accountability at study completion, all study drug will be reconciled and retained or destroyed 
according to applicable regulations. 
7.3 
Method of Assigning Patients to Treatment Groups 
This is an open-label study. After LAR consent and patient assent is received at Screening (Visit 1), 
site personnel will assign a 6-digit patient identification number to the patient. The patient 
identification number will start with the 3-digit site number assigned by the Sponsor followed by 3 
digits starting with 001, assigned by the site. 
7.4 
Blinding 
Not applicable. This is an open-label study. 
7.5 
Unblinding 
Not applicable. This is an open-label study. 
7.6 
Monitoring Treatment Compliance 
Study drug compliance will be closely monitored by capturing the date and time of each dose. 
Dosing will occur while the patient is on the inpatient unit and under direct supervision of study 
center personnel. After oral administration of study drug, a mouth check will be performed to 
verify that the dose was swallowed. 
Compliance is based on number of capsules prescribed and number of capsules taken.  
7.7 
Prior and Concomitant Medications 
7.7.1 Prior Medications 
The following prior medication restrictions apply to all patients: 
• Patients are not allowed to have received an investigational drug within 90 days or 5 half-
lives (whichever is longer) prior to Day -1; 
• Patients are not allowed to have ever taken clozapine; 
• Patients are not allowed to have used medication or herbal supplements within 14 days or 
5 half-lives (whichever is longer) prior to Day -1, with the exception of hormonal birth 
control, current antipsychotic therapy, current anti-anxiety medications, lorazepam, or 
multivitamins; 
• Current antipsychotic therapy and anti-anxiety medications (except lorazepam) must be 
washed off prior to Day -1 (see Section 7.8 for additional washout details); 

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• Use of depot antipsychotic within 3 treatment cycles prior to Day -1. 
• Use of lorazepam must be discontinued on Day -1. 
7.7.2 Concomitant Medications 
The use of concomitant medications (except oral contraceptives) during this study is prohibited, 
unless necessary to treat AEs. Any other treatment, other than study drug, is to be considered a 
concomitant medication including all prescription drugs, herbal products, vitamins, minerals, and 
over-the-counter medications. 
If the Investigator determines that a patient requires medication to treat an AE during the study, 
the Sponsor (or designee) must be contacted. 
7.8 
Washout of Antipsychotic and Anti-anxiety Medications 
Patients must be washed off current antipsychotic and anti-anxiety medications (except lorazepam) 
for a period of 4 to 7 days prior to Day 1. Patients requiring washout may be admitted to the CRU 
prior to Day -1.  An extension of the washout may be allowed with the approval of the Sponsor.  
7.9 
Special Diet or Activities 
7.9.1 Dietary Restrictions 
Patients are required to abstain from consumption of grapefruit-containing products and xanthine-
containing products (eg, coffee, energy drinks, tea, chocolate) from 24 hours prior to Day 1 dosing 
until completion of Day 6 procedures. 
Patients will be required to fast as follows: 
• For at least 10 hours prior to Screening and study drug administration on Days 1 and 5 and 
continue to fast for at least 4 hours postdose. 
• For at least 8 hours prior to study drug administration on Days 2-4 and continue to fast for 
at least 2 hours postdose.  
• On Day 6, blood will be collected for clinical laboratory tests after an overnight fast. 
Water is allowed as desired except for 1 hour before and 1 hour after study drug administration. 
Study drug will be administered with approximately 240 mL of water. 
During patient confinement, meals will be provided as follows: 
• On Days 1 through 5, patients will receive low-fat meals and snacks provided by the 
clinical site at regimented times.  
o On Days 1 and 5, lunch will be provided at approximately 4 hours postdose (ie, 
after the required 4-hour postdose fast) and dinner will be provided between 10-11 
hours postdose; snack will be provided after dinner. A snack may also be provided 
between lunch and dinner. 

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o On Days 2-4, snack will be provided at approximately 2 hours postdose (after the 
required 2-hour postdose fast on these days). Lunch, dinner, and other snacks will 
be provided at approximately the same times as Days 1 and 5.  
• On other days of confinement, meals will be provided as deemed appropriate by the clinical 
site. 
7.9.2 Alcohol and Tobacco 
During the study, patients are required to abstain from alcohol and tobacco use. 
7.9.3 Activity 
During the study, patients are required to abstain from strenuous exercise from the time of 
admission to the inpatient unit through to discharge from the CRU.  
7.10 
Treatment After Discontinuation 
Patients whose symptoms worsen or are determined by the Investigator not to be adequately 
controlled prior to completing the Open-label Treatment Period may be discontinued from the 
treatment period in order to start appropriate treatment. Patients must undergo all ET Visit 
assessments. Upon completion of ET assessments, the patient should immediately enter into the 
Standard-of-Care Stabilization Period. 
All patients who prematurely discontinue from the study should return for the Follow-up Visit. 

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8. 
SAFETY, PHARMACOKINETIC, AND OTHER ASSESSMENTS 
8.1 
Safety 
8.1.1 Adverse Events 
8.1.1.1 Definition of Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug-related. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the medicinal 
product (ICH-E2A; 21 CFR 312.32[a]). 
NOTE: Medical procedures scheduled prior to obtaining informed consent but occurring during 
the study and for a pre-existing condition which did not worsen, should not be captured as AEs 
but the medical reason for the procedure should be listed in the medical history if related to a pre-
existing condition. 
8.1.1.2 Definition of Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death 
• Is life threatening 
NOTE: An AE is considered "life-threatening" if, in the view of either the Investigator or Sponsor, 
its occurrence places the patient at immediate risk of death. It does not include an AE that, had it 
occurred in a more severe form, might have caused death. 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity, or 
• Is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based on appropriate medical judgment, they may jeopardize the 
patient and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
patient hospitalization, or the development of study medication dependency or drug abuse. 
Emergency room visits that do not result in hospitalization should be evaluated for one of the other 
serious outcomes to determine whether they qualify as SAEs. 

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8.1.1.3 Classification of Adverse Events and Serious Adverse Events 
8.1.1.3.1 
Severity 
The Investigator will provide an assessment of the severity of each AE by recording a severity 
rating on the appropriate AE reporting page of the patient’s eCRF. Severity, which is a description 
of the intensity of manifestation of the AE, is distinct from seriousness, which implies a patient 
outcome or AE-required treatment measure associated with a threat to life or functionality 
(Section 8.1.1.2). Severity will be assessed according to the following scale: 
Mild: 
A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual activities of daily living. 
Moderate: 
A type of adverse event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to the 
research patient. 
Severe: 
A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic 
intervention. 
8.1.1.3.2 
Causality Assessment 
For each AE, the Investigator must provide an assessment of causal relationship to study drug and 
each occurrence of each AE/SAE. Causal relationship must be assessed answering the following 
question: 
Is there a reasonable possibility the study medication caused the event? 
Yes: 
There is evidence to suggest a causal relationship between the study medication and 
adverse event, ie:  
• There is a reasonable temporal relationship between the study medication and the event, 
and/or 
• The event is unlikely to be attributed to underlying/concurrent disease, other 
investigational products, or other factors, and/or 
• Positive dechallenge and/or rechallenge exist 
OR 

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No: 
There is no evidence to suggest a causal relationship between the study medication 
and adverse event, ie: 
• There is no reasonable temporal relationship between the study medication and the event, 
or 
• The patient did not take the study medication, or 
• The event is likely to be attributed to underlying/concurrent disease, other investigational 
products, or other factors. 
There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is important that the 
Investigator always makes an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. The Investigator may change his/her opinion of 
causality in light of follow-up information and send an SAE follow-up report with the updated 
causality assessment. 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. The causality assessment must be 
recorded on the appropriate AE reporting page of the patient’s eCRF.  
8.1.1.4 Time Period and Frequency of AE and SAE Reporting  
The Investigator will report: 
• All AEs from the time informed consent and assent are obtained through the Follow-up 
Visit (Visit 10) 
• All SAEs, from the time informed consent and assent are obtained until 30 days after the 
last dose of study drug. At each visit, patients are to be queried regarding any AEs that 
have occurred since the previous visit. Patients will be asked to volunteer information with 
a nonleading question such as, “How do you feel since your last visit?”  
8.1.1.5 Adverse Event Reporting Procedures 
8.1.1.5.1 
Reporting Adverse Events 
All AEs, including overdose with sequelae or intentional overdose of study drug or other 
medication, must be recorded on the appropriate AE reporting page of the patient’s eCRF whether 
or not they are considered causally related to study drug. For every AE, the Investigator must: 
• Provide an assessment of the seriousness of the event (ie, is it an SAE?), as well as the severity 
and casual relationship. See Section 8.1.1.2 for the definition of SAEs and Section 8.1.1.5.2 
for SAE reporting procedures. 
• Document all actions taken with regard to study drug; 

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• Detail any other treatment measures taken for the AE 
Any AEs that are ongoing at the time of the final protocol-defined study visit will be followed 
until the condition returns to pre-study status, has resolved or stabilized, or can be explained as 
being unrelated to study drug. If a follow-up visit is deemed necessary for appropriate safety 
surveillance, it will take place within 30 days of the final protocol-defined study visit. 
8.1.1.5.2 
Reporting Serious Adverse Events 
The Sponsor is required to inform worldwide regulatory authorities of SAEs that meet specific 
criteria. Therefore, the Sponsor must be notified immediately regarding any SAE that occurs after 
informed consent and assent are obtained. 
Within 24 hours of learning of any AE that meets one of the criteria for an SAE, the study center 
personnel must report the event to the Sponsor on the SAE Form.  
If, during follow-up, any nonserious AE worsens and eventually meets the criteria for an SAE, that 
AE should be recorded as a new SAE. 
Preplanned hospitalizations (eg, elective procedures for pre-existing conditions that did not 
worsen) are excluded from SAE reporting. 
The study center must email the SAE form to the SAE email address below. Even if an initial 
report is made by telephone, the SAE form completed with all available details must still be 
emailed within 24 hours of knowledge of the event at the study center. 
Supplemental information should be submitted as soon as available and may include laboratory 
results, radiology reports, progress notes, hospital admission and emergency room notes, holding 
and observation notes, discharge summaries, autopsy reports, and death certificates. 
The Investigator is expected to take all therapeutic measures necessary for resolution of the SAE. 
Any medications or procedures necessary for treatment of the SAE must be recorded on the 
appropriate pages of the patient’s eCRF. All SAEs will be followed until resolution or stabilization. 
The Sponsor may contact the study center to solicit additional information or follow up on the 
event. 
 
 
 
 

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8.1.2 Potential Hy’s Law Cases 
Study center personnel must report every patient who meets potential Hy’s Law criteria from the 
time the ICF is signed and assent is obtained until 30 days after the final protocol-defined study 
visit or the last known dose of study drug (if the final visit does not occur).  
The criteria for potential Hy’s law cases are as follows: 
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × upper limits of 
normal (ULN) and  
• Total bilirubin ≥ 2 × ULN and  
• Alkaline phosphatase (ALP) < 2 × ULN 
Typically, all 4 analytes will be obtained from the same sample, but they may come from multiple 
samples taken within a 24-hour period.  
A laboratory alert for potential Hy’s Laws cases will be in place, and the laboratory must notify 
Investigators and the Sponsor immediately when the above criteria have been met. The Sponsor 
must be notified of any potential Hy’s Law case as soon as possible (within 24 hours of learning 
of a potential Hy’s Law case). Refer to the SAE reporting procedures (Section 8.1.1.5.2) even if 
no AE has occurred.  
Every effort to determine the cause of the liver enzyme abnormalities must be made, and close 
monitoring should be initiated in conjunction with the Study Physician and in accordance with the 
FDA Guidance for Industry: Drug Induced Liver Injury—Pre-Marketing Clinical Evaluation, 
July 2009. 
8.1.3 Pregnancy 
Study center personnel must report every pregnancy from the time the ICF was signed and assent 
was obtained until 30 days after the last dose of study drug. Within 24 hours of learning of the 
pregnancy, the study center personnel must report the event to the Sponsor on the Pregnancy Form 
and email the information even if no AE has occurred. 
Any patient who becomes pregnant must be discontinued immediately and followed to 
term/termination and the outcome reported by completing a follow-up Pregnancy Form. If the 
pregnancy is associated with an SAE (eg, if the mother is hospitalized for hemorrhage), a separate 
SAE form must be completed as described in Section 8.1.1.5.2 with the appropriate serious 
criterion (eg, hospitalization) indicated on the SAE form in addition to the Pregnancy Form. 
 
 

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8.1.4 Clinical Laboratory Determinations 
 
 During screening, the Investigator/sub-Investigator should assess the 
clinical significance of any values that are outside the reference ranges provided by the central 
laboratory; patients with abnormalities judged to be clinically significant will be excluded from 
the study. All laboratory results must be reviewed by the Investigator/sub-investigator throughout 
the open-label treatment and safety follow-up periods. Additional safety laboratory assessments 
may be scheduled at the Investigator’s discretion. 
Patients are required to fast for at least 10 hours before collection of clinical laboratory blood tests.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 

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The patient will not be eligible for inclusion in the study if she has a positive pregnancy 
test during the Screening Period. Any pregnancies that occur in females who have received 
study drug must be reported promptly to the Sponsor and the patient must be discontinued. 
Pregnancies will be followed through to termination or completion and 30 days post-
delivery to assess general health of the baby. 
All clinical laboratory results will be forwarded to the Investigator for review. Any abnormalities 
deemed clinically significant by the Investigator will be recorded as AEs in the patient’s eCRF. 
Any clinically significant abnormal laboratory values that persist should be followed by the 
Investigator in consultation with the Sponsor (or designee). Such events should be followed as 
described in Section 8.1.1. 
The Investigator should file all copies of the reports in the patient’s study chart.  
Additional details regarding sample collections, processing, and specific testing can be found in 
the Laboratory Manual. 
8.1.5 Vital Signs 
Vital signs (systolic and diastolic blood pressure [BP], pulse, temperature, and respiratory rate) 
will be assessed at every visit during the open-label treatment and stabilization periods. Weight, 
height, and BMI will be assessed as specified in the Schedule of Evaluations (Table 1-1). 
Additional vital sign measurements may be performed at the Investigator’s discretion. 
BP and radial pulse rate will be measured twice:  
• Blood pressure should be measured once after patient has been in the supine position for 
approximately 5 minutes followed by once in the standing position. The standing 
measurements should be assessed approximately 2 minutes after standing. BP may be 
measured manually or by machine.  
• Radial pulse rate should be measured after BP measurements. Radial pulse rate should only 
be measured manually and for a sufficient time to acquire an accurate measurement. 
Patients should be kept as calm and undisturbed as possible while BP and pulse rate measurements 
are taken (eg, there should be no talking while the BP is being measured). The same arm and BP 
cuff (appropriate to the arm circumference) should be used for all BP measurements. 
Whenever possible, the patient’s weight should be measured at the same time of day; the patient 
should wear his/her usual indoor clothing without jacket and shoes. For each patient, body weight 
and height should be determined using the same equipment during the study after ensuring its 
proper calibration. 

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8.1.6 Electrocardiograms 
A 12-lead ECG will be performed after the patient has rested quietly in the supine position at visits 
specified in the Schedule of Evaluations (Table 1-1). 
ECGs will be performed and electronically transmitted to a central ECG laboratory for analysis 
according to the instructions provided by the central ECG laboratory. Measurements (in msec) will 
be recorded for the following parameters: 
 
 
 
The overall interpretation and determination of the clinical significance of ECG findings using the 
interpretation from the central ECG laboratory will be the responsibility of the Investigator and 
will be recorded in the patient’s eCRF. For eligibility criteria, the values reported on the central 
ECG interpretation report, not the values that are printed on the tracing itself, will be used. 
Additional ECG assessments may be performed at the Investigator’s discretion. 
8.1.7 Other Safety Assessments 
8.1.7.1 Physical Examination 
Complete physical examinations, excluding genitourinary examinations, will be performed at the 
visits specified in the Schedule of Evaluations (Table 1-1). The examinations will be performed 
by a professionally trained physician or health professional listed on Form FDA 1572 and licensed 
to perform physical examinations. 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 

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8.1.7.4 Abnormal Involuntary Movement Scale 
The AIMS (Guy, 1976) measures facial and oral movements, extremity movements, and trunk 
movements. Seven items are rated on a scale from none (0) to severe (4). A score of “mild” (2) in 
2 or more categories or a score of “moderate” or “severe” in any 1 category results in a positive 
AIMS score (ie, the scores are not averaged). Additionally, overall severity is scored on the basis 
of severity of abnormal movements and incapacitation due to abnormal movements. The patient’s 
awareness of and distress caused by the abnormal movements are also noted. The AIMS is to be 
completed at visits as specified in the Schedule of Evaluations (Table 1-1). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.2 
Pharmacokinetic Assessments 
Blood samples for PK assessments following oral lumateperone administration will be collected 
on Days 1 and 5 
 
 
 
. 
PK parameters to be assessed are described in Section 9.7. 
 
 
 
 
 
. 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.4 
Schedule of Assessments 
The schedule of study procedures and assessments is presented by visit in the Schedule of 
Evaluations (Table 1-1). The descriptions of the procedures to be performed at each visit are 
provided below. 
If multiple assessments are scheduled at the same time (eg, 1 h post-dose), the order of assessments 
should ensure that ECG measurements and vitals are taken prior to PK samples within the 
applicable time window so that the stress of blood sampling does not impact vitals or ECG 
measurements. As guidance, the preferred order of assessments is: 
 
ECG 
 
Vitals 
 
PK 
 
Other assessments 
eg, physical exams 
 

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9. 
STATISTICAL METHODS  
9.1 
General Considerations 
The statistical analysis plan (SAP) will be finalized prior to database lock and will include a more 
technical and detailed description of the statistical analyses described in this section. This section 
is a summary of the planned statistical analyses of safety. 
9.2 
Determination of Sample Size 
 
 
 
 
 
9.3 
Analysis Populations 
The following analysis populations will be considered in the statistical analysis of the study: 
• The Enrolled Set includes all patients whose LAR provided informed consent and all 
patients who provided written assent. 
• Safety Set includes all patients who take at least 1 dose of study drug. 
• The Pharmacokinetic Set includes all patients who take at least 1 dose of study drug and 
had at least one evaluable PK parameter and had no major protocol deviation that may 
impact PK analyses. Patients who experience emesis within 2 times the median Tmax after 
receiving one oral lumateperone dose may be excluded from the PK analysis. 
9.4 
Patient Disposition 
The number of patients who were screened, failed screening and enrolled in the study will be 
summarized overall. 
The number and percentage of patients who completed the Open-label Treatment Period and who 
prematurely discontinued from the Open-label Treatment Period will be summarized overall (and 
by dose if more than one dose is administered) and by reason for premature discontinuation. 
9.4.1 Demographics and Other Baseline Characteristics 
Demographic parameters (eg, age, race, ethnicity, sex, weight, height, BMI) and other baseline 
characteristics will be summarized overall (and by dose if more than one dose is administered). 
Descriptive statistics (n, mean, median, SD, minimum, and maximum) will be presented for 
continuous variables. Frequency distributions (counts and percentages) will be presented for 
categorical variables. 

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Medical and surgical history and physical findings will be summarized overall (and by dose if 
more than one dose is administered), by System Organ Class (SOC) and preferred term. 
9.4.2 Extent of Exposure and Treatment Compliance 
9.4.3 Extent of Exposure 
Exposure to study drug during Open-label Treatment Period will be summarized for treatment 
duration, calculated as the number of days from the date of the first dose of study drug taken to the 
date of the last dose taken, inclusive. Descriptive statistics (n, mean, median, SD, minimum, and 
maximum) will be presented overall (and by dose if more than one dose is administered). 
9.4.4 Prior and Concomitant Medication 
Prior and concomitant medication use will be listed with the therapeutic class included.  
9.5 
Efficacy Analyses 
Not applicable. 
9.6 
Safety Analyses 
The safety analysis will be performed based on the Safety Set as specified in the SAP. Safety 
variables will include AEs, clinical laboratory parameters, vital signs, ECG parameters, 
 
 AIMS 
 results. For each safety parameter, the last assessment made 
before the first dose of open-label study drug will be used as the baseline for all analyses of that 
safety parameter. 
The safety data from the first 4 patients will be reviewed prior to continuing with the 42 mg dose 
in the remaining patients. If lumateperone 42 mg is not tolerated, the remaining patients will be 
administered open-label lumateperone 28 mg. 
9.6.1 Adverse Events 
Adverse events will be coded by SOC and preferred term using the most recent version of the 
Medical Dictionary for Regulatory Activities (MedDRA).  
An AE will be considered a treatment-emergent AE (TEAE) if it was not present before the first 
dose of open-label study drug or was present before the first dose of open-label study drug but 
increased in severity after the first dose. If more than one AE is reported before the first dose of 
open-label study drug and coded to the same preferred term, the AE with the greatest severity will 
be used as the benchmark for comparison with the AEs occurring during the Open-label Treatment 
Period that were also coded to that preferred term. An AE that occurs more than 1 day after the 
last dose of open-label study drug will not be counted as a TEAE. 
The number and percentage of patients reporting TEAEs will be tabulated overall (and by dose if 
more than one dose is administered), by SOC and preferred term; by SOC, preferred term, and 
severity; and by SOC, preferred term, and relationship to study drug. If more than one AE is coded 

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to the same preferred term for the same patient, the patient will be counted only once for that 
preferred term using the most severe and most related occurrence for the summary by severity and 
by relationship to study drug. 
Additional details pertaining to analyses of AE data will be provided in the SAP. 
9.6.2 Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values (in SI and conventional units) at baseline, 
postbaseline, and changes from baseline values at each assessment timepoint will be summarized 
overall (and by dose if more than one dose is administered) for the Safety Set for each clinical 
laboratory parameter. 
 
 
 
 
9.6.3 Vital Signs 
Descriptive statistics for vital signs (eg, pulse rate, systolic and diastolic BP, body weight and 
height) at baseline, postbaseline, and changes from baseline values at each assessment timepoint, 
and at the end of the study will be presented overall (and by dose if more than one dose is 
administered) for the Safety Set. 
 
 
 
 
9.6.4 Electrocardiogram 
Descriptive statistics for ECG parameters 
 
at baseline, postbaseline, and changes from baseline values at each assessment timepoint will be 
summarized overall (and by dose if more than one dose is administered) for the Safety Set.  
 
 
 

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9.6.5 Other Safety Parameters 
Descriptive statistics for 
, and AIMS at baseline, postbaseline, and changes 
from baseline values at each assessment timepoint for each of these assessments will be 
summarized overall (and by dose if more than one dose is administered) for the Safety Set.  
For the C-SSRS, the number and percentage of patients who have suicidal ideation or suicidal 
behavior will be summarized overall (and by dose if more than one dose is administered) for the 
Safety Set.  The details will be provided in the SAP. 
9.7 
Plasma Concentration Parameters 
The following PK parameters will be calculated for Days 1 and 5 for lumateperone 
 
 using noncompartmental methods: 
• Time of maximum concentration of drug in plasma (Tmax) 
• Maximum plasma drug concentration (Cmax)  
• Whenever possible, relative ratios of metabolite to parent will be calculated 
• Area under the plasma concentration time curve (AUC) from time zero to the last measurable 
concentration (AUC0-t) 
• AUC from time zero to the end of the dosing interval, tau (AUC0-tau) 
• Area under the plasma concentration time curve (AUC) from time zero to infinity (AUC0-inf) – 
only for Day 1, as data permit 
• 
 
• Terminal elimination half-life (t½) 
• Apparent oral clearance (CL/F) 
 
• Apparent volume of distribution (VZ/F)  
 
For Day 1 AUC calculations, the predose concentration on Day 2 will serve as the 24-hour 
measurement post Day 1 dose administration. 
Individual plasma concentrations will be presented in data listings. Plasma concentration data will 
be summarized over time (and by dose, if applicable) using descriptive statistics. Mean and 
individual plasma concentration versus time profiles will be presented in figures on both linear 
and semi-logarithmic scales. The individual PK parameters will be presented in data listings and 
summarized using descriptive statistics. Geometric means will be included for Cmax, AUC0-t, 
AUC0-inf, AUC0-tau, CL/F, and Vz/F. 
 
 
 
 

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9.8 
Interim Analysis 
After the first 4 patients have received lumateperone 42 mg and completed the Open-label 
Treatment Period, safety data and, if available, PK data will be reviewed to confirm the dose 
recommendation for the remaining patients.  
 
 
  
 
 
9.9 
Protocol Deviations 
A deviation from the protocol is an unanticipated departure from the procedures or processes 
approved by the Sponsor and the IRB and agreed to by the Investigator. A major protocol deviation 
occurs when there is nonadherence to the protocol by the patient or Investigator that results in a 
significant, additional risk to the patient, or to the primary efficacy assessment. Major protocol 
deviations can include, for example, nonadherence to inclusion or exclusion criteria or 
nonadherence to ICH GCP guidelines and may lead to the patient being withdrawn from the study. 
The Investigator or designee must document and explain any deviation from the approved 
protocol. The IRB should be notified of all major protocol deviations in a timely manner in 
accordance with IRB reporting procedures. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL MONITORING 
10.1 
Study Termination 
The Sponsor reserves the right to terminate the study in its entirety or at a specific study center 
before study completion.  
10.2 
Investigator Obligations 
10.2.1 Documentation 
The Investigator must provide the following to the Sponsor or its designee, before the start of the 
study: 
• A completed and signed Form FDA 1572. If, during the course of the study, any changes 
are made that are not reflected on Form FDA 1572, a new Form FDA 1572 must be 
completed and returned to the Sponsor for submission to the FDA 
• A fully executed contract 
• The curricula vitae for the Investigator and all sub-investigators listed on Form FDA 1572, 
including a copy of each physician’s license 
• Financial disclosure agreement completed and signed by the Investigator and all Sub-
investigators listed on Form FDA 1572.  
• A copy of the original IRB approval for conducting the study. If the study is ongoing, 
renewals must be submitted at yearly intervals. All subsequent modifications must be 
submitted and approved by the IRB, as stated in Section 6.6. 
• A copy of the IRB-approved ICF and age-appropriate assent form 
• A copy of the HIPAA authorization form, or other applicable local privacy forms 
• A list of the IRB members or the US Department of Health and Human Services general 
assurance number 
• The Investigator’s Statement page in this protocol signed and dated by the Investigator 
10.2.2 Performance 
The Investigator must demonstrate reasonable efforts to recruit qualified adolescent patients for 
the study. 
10.2.3 Use of Investigational Materials 
Study drug must be stored in a secured place and must be locked. At study initiation, a 
representative from the Sponsor will inventory the study drug at the study center. The Investigator 
must maintain adequate records documenting the receipt and disposition of all study supplies. The 
Sponsor may supply forms on which to record the date the study drug was received and a 
dispensing record in which to record each patient’s use. All unused study drug must be returned to 
the Sponsor-designated central depot.  

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10.2.4 Case Report Forms 
All patient data relating to the study, except for data electronically transmitted (eg, central 
laboratory results), will be recorded on eCRFs to be provided by the Sponsor through the EDC 
system. The Investigator is responsible for verifying that all data entries in the eCRFs are accurate 
and correct by electronically signing the completed eCRFs submitted to the Sponsor. The 
Investigator must maintain and retain accurate documentation that supports the information 
entered into the EDC system for source document verification and possible regulatory inspection. 
10.2.5 Retention and Review of Records 
Records and documents pertaining to the conduct of this study, including eCRFs, source 
documents (eg, medical records, laboratory reports), consent forms, regulatory documents, and 
medication inventory records must be retained by the Investigator for a period of at least 15 years 
after study completion unless local regulations or institutional policies require a longer retention 
period or otherwise notified in writing by the Sponsor. 
No study records shall be destroyed without notifying the Sponsor and providing the Sponsor the 
opportunity to arrange long-term storage for such study records or authorizing in writing the 
destruction of records after the required retention period. 
The Investigator must permit access to any documentation relating to the study upon request of 
the Sponsor or applicable regulatory authorities. If the Investigator for the study retires, relocates, 
or for other reasons withdraws from the responsibility of keeping the study records, custody must 
be transferred to a suitable alternate custodian employee of the institution or to a suitably qualified 
and responsible third party. The Sponsor must be notified in writing of the name and address of 
the new custodian in advance of the transfer. 
10.2.6 Patient Confidentiality 
All patient records will be identified by patient identification number only. Patients’ names are not 
to be transmitted to the Sponsor. The Investigator will keep a master patient list on which the 
patient identification number and the full name, address, and telephone numbers of each patient 
and patient’s LAR are listed. 

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10.3 
Data Quality Assurance 
10.3.1 Data Monitoring 
Before any patient enters the study, a representative of the Sponsor will meet with the Investigator 
and the study center personnel to review the procedures to be followed during the study. Electronic 
data capture (EDC) functionality training is provided via computer-based training to train 
Investigators and authorized designees on recording the data in the eCRFs using the EDC system.  
The Investigator will maintain complete source documents (eg, signed ICFs, written or electronic 
medical records, pharmacy records). Source documents provide evidence for the existence of study 
patients and substantiate the integrity of the data collected in the eCRF. The Investigator will make 
available to the study monitor or designee source documents (written notes and electronic medical 
records, if used), signed ICFs, and all other study-related documents. 
Study monitors or designees, appointed by the Sponsor, will perform ongoing source document 
verification to confirm that data entered into the eCRF are accurate, complete, and verifiable from 
source documents; that the safety and rights of patients are protected; and that the study is 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. After the first patient is enrolled, the study 
monitor or designee, will periodically monitor the progress of the study by conducting on-site 
visits. In addition to on-site source document verification, study monitors will review study 
progress remotely, possibly warranting more frequent communication and/or study center visits. 
Details of monitoring activities are provided in the Monitoring Plan. 
10.3.2 Data Recording and Documentation 
Data collection will involve the use of the EDC system, to which only authorized personnel will 
have access. Patient data are to be entered into the EDC system by the Investigator or designee 
using their assigned EDC user account. The Investigator or designee will record all patients’ study 
data in the eCRF, unless the data are transmitted to the Sponsor electronically (eg, laboratory data). 
Data entered in the eCRF must be consistent with the source documents or the discrepancies must 
be explained. The Investigator is responsible for verifying that all data entries are accurate and 
correct. The Investigator may need to request previous or external medical records to support study 
data. 
The Sponsor is responsible for the data management of this study, including quality checking of 
the data. The Sponsor or designee will review study data for completeness, logic, and protocol 
adherence, using a combination of manual review and programmatic edit checks. After data entry 
into the EDC system by the Investigator or designee, a combination of manual and programmatic 
edit checks will be used to review the data for completeness, logic, and adherence to study 
protocol. As a result of these edit checks, data monitoring, and reviews, queries may be 
electronically issued to the study center and should be answered electronically via the EDC system. 
Each query will carry identifying information (assigned username, date, and time) to assist the 
Sponsor and the Investigator on the origin of the data clarification request and the response 
provided by the Investigator. All data changes made to patient’s data via a data query will be 
approved by the Investigator prior to final database lock. 

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The Investigator or designee will be responsible for approving all changes performed on the data 
and endorsing the patient data within the EDC system. This approval method will include applying 
an electronic signature linked to a uniquely assigned username and password that together will 
represent a traditional handwritten signature used in the past. After all data have been reviewed 
and all issues have been resolved, the database will be locked. 
All data collected in the context of this study will be stored and evaluated per regulatory 
requirements and applicable guidance for electronic records. Also, data will be stored and 
evaluated in such a way as to guarantee patient confidentiality in accordance with the legal 
stipulations applying to confidentiality of data. Study records (eg, copies of eCRFs, laboratory 
reports, and regulatory documents) will be retained at the study center, along with adequate source 
documentation, according to FDA and ICH requirements. All study records must be available for 
inspection by the Sponsor, its authorized representatives, the FDA, or other health authorities. 
Source documents will be used at the study centers and may include a patient’s medical record, 
hospital charts, clinic charts, the Investigator’s patient study files, as well as the results of 
diagnostic tests such as laboratory tests, ECGs, etc. A centralized clinical laboratory will be used 
for the analysis of all blood samples. Additional information on the collection and handling of 
samples is detailed in the Laboratory Manual. 
 
 
 
 

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11. 
REFERENCES  
Barnes TR (1989). A rating scale for drug-induced akathisia. Br J Psychiatry. 154:672-6. 
Centers for Disease Control (2000). 2 to 20 years: Boys and Girls body mass index-for-age 
percentiles. http://www.cdc.gov/growthcharts. Accessed 24 April 2020. 
Correll CU. Antipsychotic use in children and adolescents: minimizing adverse effects to 
maximize outcomes (2008). J Am Acad Child Adolesc Psychiatry. 47(1):9-20. 
Driver DI, Gogtay N, and Rapoport JL. Childhood onset schizophrenia and early onset 
schizophrenia spectrum disorders (2013). Child Adolesc Psychiatric Clin N Am. 22(4):539-555. 
FDA Guidance for Industry: Drug Induced Liver Injury—Pre-Marketing Clinical Evaluation, 
July 2009. 
FDA Guidance for Industry: General Clinical Pharmacology Considerations for Pediatric Studies 
for Drugs and Biological Products (Draft Guidance December 2014. 
Gochman P, Miller R, and Rapoport JL (2011). Curr Psychiatry Rep.13(5):321-322. 
Guy W, editor (1976). ECDEU Assessment Manual for Psychopharmacology. Rockville: U.S. 
Department of Health Education, and Welfare.  
Hollis C (2000). Adolescent schizophrenia. Advances in Psychiatric Treatment. 6:83- 92. 
ICX-B139: Modeling and Simulation Analysis Report—Population Pharmacokinetic-
Pharmacodynamic Modeling of Efficacy and Safety of Lumateperone Tosylate (ITI-007) in 
Patients with Acute Exacerbation of Schizophrenia (September 25, 2019). 
Kumra S, Oberstar JV, Sikich L et al (2008). Efficacy and tolerability of second-generation 
antipsychotics in children and adolescents with schizophrenia. Schizophr Bull. 34(1):60-71. 
National Institute of Mental Health (2020). 
https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml. Accessed 24 April 2020. 
Simpson GM. Angus JW. A rating scale for extrapyramidal side effects (1970). Acta Psychiat 
Scand Suppl. 212:11–9. 
Wang Y, Jadhav PR, Lala M, and Gobburu JV. Clarification on precision criteria to derive 
sample size when designing pediatric pharmacokinetic studies (2012). J Clin Pharmacol. 
52:1601-1606. 

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12. 
APPENDICES 
Appendix I. Elements of Informed Consent 
Procedures will comply with 21 CFR, Parts 50 (Subpart D) and 312. Signed informed consent will 
be obtained from the LAR for each patient participating in a clinical research study and assent will 
be obtained from the patient. The consent must include the following items: 
• A statement that the study involves research and an explanation of the purposes of the 
research; a description of the procedures to be followed and the identification of any 
procedures that are experimental; and the expected duration of the patient’s participation 
• A description of any reasonably foreseeable risks or discomforts to the patient 
• A description of any benefits to the patient or to others that may reasonably be expected 
from the research. If the patient is to be paid for participating in the study, the consent form 
must state the amount that he/she will receive and the schedule of payment (to ensure 
neither coercion nor undue influence). 
• A disclosure of appropriate alternative procedures or courses of treatment, if any, that 
might be advantageous to the patient 
• A statement describing the extent, if any, to which confidentiality of records identifying 
the patient will be maintained and noting the possibility that the FDA, the Sponsor, the 
IRB, or an authorized contract research organization may inspect the records 
• For research involving more than minimal risk, an explanation of whether any medical 
treatment is available if injury occurs and, if so, what it consists of or where further 
information may be obtained 
• An explanation of whom to contact, including the relevant telephone number, for answers 
to pertinent questions about the research and the research patient’s rights and whom to 
contact in the event of a research-related injury to the patient. (Note: In some cases, it may 
be necessary to identify a person other than the Investigator as the contact. The guidance 
of the IRB may be required.) 
• A statement that participation is voluntary, that refusal to participate will involve no 
penalty or loss of benefits to which the patient is otherwise entitled, and that the patient 
may discontinue participation at any time without penalty or loss of benefits to which the 
patient is otherwise entitled 
• A statement that the particular treatment or procedures may involve risks to the patient (or 
to the embryo or fetus if the patient may become pregnant) that are at present unforeseeable 
• The expected circumstances for which the patient’s participation may be terminated by the 
Investigator without regard to LAR consent 
• Any additional costs to the patient that may result from participation in the research 
• The consequences of a patient’s or LAR’s decision to withdraw from the research and 
procedures for an orderly termination of the patient’s participation 

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• A statement that significant new findings developed during the course of the research that 
may relate to the patient’s willingness to continue participation will be provided to the 
patient’s LAR. 
• The approximate number of patients involved in the study 
• A statement of permission providing LAR consent for the patient to participate (eg, “I agree 
to participate . . .”) and patient assent to participate 
• A place for the LAR’s signature and date of signing of the ICF  
• A statement indicating that information about this study has been, or will be, entered into 
a databank that is publicly accessible at www.ClinicalTrials.gov. 
• A copy of the signed consent form must be given to the patient and LAR. 
 
Appendix II. Protocol Version 4.0–Summary of Changes 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 1-Synopsis: Statistical 
 
 
 
 
 
 
 

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Protocol Section 
Revision  
Rationale 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol Section 
Revision  
Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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13. 
INVESTIGATOR SIGNATURE PAGE 
INVESTIGATOR SIGNATURE PAGE 
I agree to conduct Study ITI-007-020 in accordance with this protocol, dated 28 Feb 2022, and 
with all applicable government regulations and GCP guidance, including all statements regarding 
confidentiality, and according to local legal and regulatory requirements and applicable US federal 
and/or local regulations and ICH guidelines. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without prior authorization from Intra-Cellular Therapies, Inc. 
_____________________________________ 
_____________________ 
Principal Investigator Signature 
Date 
_____________________________________ 
 
______________________ 
Principal Investigator Name (printed) 
 
 
Site Number 

Signature Page for VV-CLIN-000938 v1.0