An Open-label, Multicenter Trial to Assess the Safety and Tolerability of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
Phase: PHASE3
Conditions: Major Depressive Disorder
Sponsor: Intra-Cellular Therapies, Inc.

NCT05061719 
 
 
 
 
Study ID: ITI-007-503 
 
 
 
Title: An Open-label, Multicenter Trial to Assess the Safety and Tolerability of 
Lumateperone as Adjunctive Therapy in the Treatment of Patients with Major Depressive 
Disorder 
 
 
Protocol Amendment 1 Date: 23 Aug 2021 

MDD Open-label Safety Study-Amendment 1 
Protocol ITI-007-503 
Intra-Cellular Therapies, Inc. 
23 Aug 2021 
Confidential 
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PROTOCOL AMENDMENT #1: MAJOR CHANGES 
Protocol Amendment 1 for Study ITI-007-503, dated 23 Aug 2021, provides revisions and 
clarifications to the Original Protocol (dated 05 May 2021). Major changes to the protocol are 
summarized in the table below. 
Editorial corrections and minor revisions for consistent terminology usage are not summarized in 
this table. 
Protocol Section 
Revision  
Rationale 
Section 6.3.1 Inclusion Criteria 
Added statement noting that VCT will 
continue to monitor for patient participation 
in other clinical trials. 
Clarification 
Section 6.4 Stopping Criteria 
Updated the section title; modified 
discontinuation and patient-level stopping 
criteria (Section 6.4.1); and added a 
subsection for study stopping criteria 
(Section 6.4.2); 
Based on feedback from 
FDA on ITI-007-501 
protocol. 
Section 7.1 Study Treatment, 
Supply (Section 7.1.1) and 
Storage (Section 7.1.2) Study 
Drug 
Updated study treatment supply and storage 
information 
Clarifications 
Section 8.2.4 Clinical 
Laboratory Determination; 
Section 8.3 Pharmacokinetic 
Assessments; Section 10.3.2 
Data Recording and 
Documentation  
Changed Laboratory Procedure Manual to 
Laboratory Manual 
Revised to be consistent 
with nomenclature for 
study site materials. 
Section 9.4.5.1 Adverse Events 
Statistical Methods 
Clarified the definition of treatment-
emergent adverse events during the open-
label treatment period. 
Clarification 
Section 9.4.5.5.1 Columbia 
Suicide Severity Rating Scale 
Revised the planned analyses of C-SSRS 
data. 
Revision 

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PROTOCOL APPROVAL—SPONSOR SIGNATORIES 
Protocol Title: 
An Open-label, Multicenter Trial to Assess the Safety and 
Tolerability of Lumateperone as Adjunctive Therapy in the 
Treatment of Patients with Major Depressive Disorder 
Protocol Number: 
ITI-007-503 
Original Protocol Date: 
23 Aug 2021 
DocuSign Envelope ID: 39CA4D89-C0EE-4466-A318-3BE081AB39C2

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TABLE OF CONTENTS 
TITLE PAGE .................................................................................................................................. 1 
PROTOCOL AMENDMENT #1: MAJOR CHANGES ................................................................ 2 
PROTOCOL APPROVAL—SPONSOR SIGNATORIES ............................................................ 3 
TABLE OF CONTENTS ................................................................................................................ 4 
LIST OF TABLES .......................................................................................................................... 7 
LIST OF ABBREVIATIONS ......................................................................................................... 8 
1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF EVALUATIONS ................................... 10 
2. 
ETHICAL CONSIDERATIONS .......................................................................................... 16 
2.1 
Institutional Review Board and Independent Ethics Committee ................................... 16 
2.2 
Ethical Conduct of the Study ......................................................................................... 16 
2.3 
Patient Information and Informed Consent .................................................................... 16 
3. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ........................... 17 
4. 
INTRODUCTION ................................................................................................................ 18 
5. 
STUDY OBJECTIVES ......................................................................................................... 20 
6. 
INVESTIGATIONAL PLAN ............................................................................................... 21 
6.1 
Overall Study Design and Plan ...................................................................................... 21 
6.2 
Scientific Rationale for Study Design ............................................................................ 22 
6.2.1 
Study Design ........................................................................................................... 22 
6.2.2 
Dose Selection ........................................................................................................ 22 
6.3 
Study Population ............................................................................................................ 22 
6.3.1 
Inclusion Criteria .................................................................................................... 22 
6.3.2 
Exclusion Criteria ................................................................................................... 23 
6.4 
Stopping Criteria ............................................................................................................ 24 
6.4.1 
Discontinuation of Patients from Therapy or Assessment: Patient-level Stopping 
Criteria 24 
6.4.2 
Study Stopping Criteria........................................................................................... 24 
6.5 
Patient Replacement Procedures .................................................................................... 25 
6.6 
Changes in the Conduct of the Study ............................................................................. 25 
7. 
STUDY TREATMENTS ...................................................................................................... 26 
7.1 
Lumateperone ................................................................................................................. 26 
7.1.1 
Supply of Lumateperone ......................................................................................... 27 
7.1.2 
Storage of Lumateperone ........................................................................................ 27 
7.2 
Adjunctive Background Antidepressant Therapy .......................................................... 27 

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7.3 
Lumateperone Accountability ........................................................................................ 27 
7.4 
Method of Assigning Patients to Treatment Groups ...................................................... 27 
7.5 
Blinding .......................................................................................................................... 28 
7.6 
Unblinding ...................................................................................................................... 28 
7.7 
Monitoring Treatment Compliance ................................................................................ 28 
7.8 
Prior and Concomitant Medications ............................................................................... 28 
7.8.1 
Prior Medications .................................................................................................... 28 
7.8.2 
Prohibited Medications ........................................................................................... 28 
7.8.3 
Rescue Medications ................................................................................................ 29 
7.9 
Treatment after Discontinuation ..................................................................................... 29 
8. 
EFFECTIVENESS, SAFETY, AND OTHER ASSESSMENTS ......................................... 30 
8.1 
Effectiveness Assessments ............................................................................................. 30 
8.1.1 
Montgomery-Åsberg Depression Rating Scale (MADRS)..................................... 30 
8.1.2 
Clinical Global Impression-Severity ....................................................................... 30 
8.2 
Safety .............................................................................................................................. 30 
8.2.1 
Adverse Events ....................................................................................................... 30 
8.2.2 
Potential Hy’s Law Cases ....................................................................................... 34 
8.2.3 
Pregnancy ................................................................................................................ 34 
8.2.4 
Clinical Laboratory Determinations ....................................................................... 35 
8.2.5 
Vital Signs ............................................................................................................... 36 
8.2.6 
Electrocardiograms ................................................................................................. 36 
8.2.7 
Other Safety Assessments ....................................................................................... 37 
8.3 
Pharmacokinetic Assessments ........................................................................................ 38 
8.4 
Schedule of Assessments ............................................................................................... 40 
8.4.1 
Screening/Baseline Visit (Visit 1/Day 1) ................................................................ 40 
8.4.2 
Open-label Treatment Period .................................................................................. 41 
8.4.3 
Safety Follow-up Visit (Visit 17/Week 28) ............................................................ 44 
9. 
STATISTICAL METHODS ................................................................................................. 45 
9.1 
General Considerations .................................................................................................. 45 
9.2 
Determination of Sample Size ........................................................................................ 45 
9.3 
Analysis Populations ...................................................................................................... 45 
9.4 
Statistical Analyses ........................................................................................................ 45 
9.4.1 
Patient Disposition .................................................................................................. 45 
9.4.2 
Demographics and Other Baseline Characteristics ................................................. 46 

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9.4.3 
Extent of Exposure and Treatment Compliance ..................................................... 46 
9.4.4 
Efficacy Analyses ................................................................................................... 47 
9.4.5 
Safety Analyses ....................................................................................................... 47 
9.4.6 
Plasma Concentration Parameters ........................................................................... 49 
9.5 
Interim Analysis ............................................................................................................. 49 
9.6 
Data and Safety Monitoring Board ................................................................................ 49 
9.7 
Protocol Deviations ........................................................................................................ 49 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL MONITORING ............. 50 
10.1 
Study Termination ...................................................................................................... 50 
10.2 
Investigator Obligations ............................................................................................. 50 
10.2.1 Documentation ........................................................................................................ 50 
10.2.2 Performance ............................................................................................................ 50 
10.2.3 Use of Investigational Materials ............................................................................. 50 
10.2.4 Case Report Forms .................................................................................................. 51 
10.2.5 Retention and Review of Records ........................................................................... 51 
10.2.6 Patient Confidentiality ............................................................................................ 51 
10.3 
Data Quality Assurance .............................................................................................. 51 
10.3.1 Data Monitoring ...................................................................................................... 51 
10.3.2 Data Recording and Documentation ....................................................................... 52 
10.4 
Reporting and Publication .......................................................................................... 53 
11. 
REFERENCES .................................................................................................................. 54 
12. 
APPENDICES ................................................................................................................... 55 
Appendix I. 
Elements of Informed Consent ............................................................................ 55 
13. 
INVESTIGATOR SIGNATURE PAGE ........................................................................... 57 
 

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LIST OF TABLES 
Table 1-1: Schedule of Evaluations .............................................................................................. 13 
Table 7-1: Lumateperone Dosage and Composition .................................................................... 26 
 
 

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LIST OF ABBREVIATIONS 
ADT 
Antidepressant treatment 
AE 
adverse event 
AIMS 
Abnormal Involuntary Movement Scale 
ALT 
alanine aminotransferase  
AST 
aspartate aminotransferase 
β-hCG 
human chorionic gonadotropin 
BARS 
Barnes Akathisia Scale 
BMI 
body mass index 
BP 
blood pressure 
C–SSRS 
Columbia–Suicide Severity Rating Scale 
CFR 
Code of Federal Regulations 
CRO 
Contract research organization 
CSR 
Clinical study report 
DSM-5 
Diagnostic and Statistical Manual, 5th edition 
ECG 
electrocardiogram, electrocardiographic 
eCRF 
electronic case report form 
ECT 
electroconvulsive therapy 
EDC 
electronic data capture 
ET 
early termination 
FDA 
Food and Drug Administration 
FOCBP 
Female of childbearing potential 
FR 
Federal Register 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
ICH 
International Council on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for 
Human Use 
IEC 
International Ethics Committee 
IND 
Investigational New Drug (application) 
IRB 
Institutional Review Board 
ITI 
Intra-Cellular Therapies, Inc. 
IWRS 
Interactive Web Response System 
MADRS 
Montgomery-Åsberg Depression Rating Scale 
MDD 
major depressive disorder 
MDE 
major depressive episode 
PK 
pharmacokinetic 
QTc 
QT interval corrected for heart rate 
QTcB 
QT interval corrected for heart rate using the Bazett formula 
(QTcB = QT/<RR>½) 
QTcF 
QT interval corrected for heart rate using the Fridericia 
formula (QTcF = QT/<RR>⅓) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Simpson Angus Scale 

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SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
UDS 
urine drug screen 
ULN 
upper limit of normal 

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1. 
PROTOCOL SYNOPSIS AND SCHEDULE OF EVALUATIONS 
CLINICAL STUDY SYNOPSIS: Study ITI-007-503 
Title of Study 
An Open-label, Multicenter Trial to Assess the Safety and 
Tolerability of Lumateperone as Adjunctive Therapy in the 
Treatment of Patients with Major Depressive Disorder 
Study Centers (Country) 
Approximately 120 study centers (US and Non-US) 
Development Phase 
Phase 3 
Objectives 
Primary Objective 
To evaluate the safety and tolerability of lumateperone 42 mg 
administered orally once daily for approximately 26 weeks as 
adjunctive treatment to antidepressant therapy (ADT) in patients 
with major depressive disorder (MDD). 
Secondary Objectives 
To evaluate whether lumateperone 42 mg administered orally 
once daily for approximately 26 weeks as adjunctive treatment to 
ADT improves or maintains improvement of depressive 
symptoms in patients with MDD as measured by change from 
baseline in the Montgomery-Åsberg Depression Rating Scale 
(MADRS) total score and in the Clinical Global Impression Scale-
Severity (CGI-S) score.  
Study Design 
This is an international, multicenter, open-label, fixed dose, 
26-week study of patients with MDD. Eligible patients from the 
lead-in studies will enter the Open-label Safety Study at the 
Screening/Baseline Visit (Visit 1/Day 1), at which point patient 
eligibility will be assessed and informed consent obtained.  
At the Screening/Baseline Visit (Visit 1/Day 1), which is the same 
visit as Visit 8/Day 43 of the lead-in study, eligible patients will 
receive open-label lumateperone 42 mg once daily for 
approximately 26 weeks. Patients will continue their background 
ADT from the lead-in study. Patients will be seen for weekly visits 
through Visit 5/Week 4. Thereafter, visits will occur every two 
weeks. A Safety Follow-up visit will occur on Visit 17/Day 197, 
approximately 2 weeks after the last dose of open-label 
lumateperone 42 mg. 
Number of Patients 
Approximately 760 patients are planned to be enrolled in the 
Open-label Safety Study. No de novo patients will be enrolled. 

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Diagnosis and Main Criteria for 
Inclusion and Exclusion 
Main Inclusion Criteria 
Each patient entering the Open-label Safety Study must meet all 
of the following criteria: 
1. In the opinion of the Investigator, the patient must have 
safely completed the lead-in study. 
2. The patient must understand the written informed consent 
for the Open-label Safety Study, provide signed and 
witnessed written informed consent. 
3. The patient is taking his/her ADT as prescribed from the 
lead-in study. 
4. The patient must agree to continue using highly effective 
methods of birth control as specified in the lead-in study 
through the Safety-Follow-up Period of the Open-label 
Safety Study, or female patients or female partners of male 
patients must be of non-childbearing potential. 
All Inclusion Criteria are presented in Section 6.3.1. 
Main Exclusion Criteria 
Because all patients enrolled in the lead-in study were required to 
satisfy exclusion criteria for participation in the lead-in study, the 
Investigator should assess if there has been any change in patient 
health status. Any newly-emergent medical condition reported 
during the lead-in study must be evaluated by the Investigator and 
should be discussed with the Sponsor or designee before enrolling 
the patient in the study. 
Patients enrolling directly from the lead-in study to the Open-label 
Safety Study at Visit 1/Day 1 will be excluded if they meet the 
following criteria: 
1. In the opinion of the Investigator, the patient is unable to 
comply with study procedures or judged to be 
inappropriate for the study; 
2. In the opinion of the Investigator, the patient has a 
significant risk for suicidal behavior during the course of 
her/his participation in the study or is considered to be an 
imminent danger to her/himself or others, and/or: 
a. 
At the Screening/Baseline Visit (Visit 1/Day 1) the 
patient scores “yes” on Suicidal Ideation Items 4 
and 5 of the C-SSRS since the last visit version 
(Visit 7/Week 5 of the lead-in studies); 
b. 
At the Screening/Baseline Visit (Visit 1/Day 1), 
the patient scores > 5 on MADRS Item 10 
(Suicidal Thoughts); 
3. Based on the Investigator’s clinical judgement, any 
abnormal clinical laboratory tests results obtained 
throughout the lead-in study that are considered 
clinically significant and preclude safe participation in 
the study. 
All Exclusion Criteria are presented in Section 6.3.2. 
 Duration of Study 
Study duration will be approximately 26 weeks of open-label 
treatment, followed by a 2-week Safety Follow-up.  
Investigational Product, Dosage, and 
Mode of Administration 
Lumateperone 42 mg capsules, 42 mg/day adjunctive to ongoing 
background ADT, oral administration. 

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Criteria for Evaluation 
Safety Measures 
AE recording, clinical laboratory measures, vital signs, 
electrocardiograms (ECGs), and physical examination; measures of 
extrapyramidal symptoms: Abnormal Involuntary Movement Scale 
(AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson 
Angus Scale (SAS); Columbia-Suicide Severity Rating Scale 
(C-SSRS); and pregnancy test (if applicable). 
Efficacy Endpoints 
Change from baseline in MADRS total score and CGI-S score. 
Pharmacokinetic Measures 
Optional blood samples for pharmacokinetic (PK) analysis of 
lumateperone and metabolites (IC200131, IC200161, IC200565, 
IC201308, and IC201309) will be collected. Three blood samples 
will be collected at Visit 2 at predose, between 0.5-to-1-hour 
postdose, and between 1.5 to 3 hours postdose. One sample will be 
collected at Visit 7. 
Statistical Methods and Sample Size 
Approximately 760 patients will be enrolled. The sample size is not 
based on statistical considerations, but is based on the number of 
patients who may be eligible based on participation in the lead-in 
study. It is expected that the majority of patients who safely 
complete the lead-in study will continue treatment for the full 26 
weeks. 
All safety parameters will be summarized descriptively. Safety 
analyses will be based on the Safety Population defined as all 
patients who received at least one dose of open-label lumateperone 
42 mg. 
Analyses of efficacy endpoints will be performed based on the 
patients in the Safety Population who have an available baseline 
efficacy value and at least one postbaseline efficacy assessment 
during the Open-label Treatment Period. Analyses will primarily 
consist of change from baseline descriptive summaries of MADRS 
total score and CGI-S scores. 
Individual plasma concentrations of lumateperone and metabolites 
will be listed and summarized by visit/timepoint. Plasma 
concentrations of lumateperone and potentially of selected 
metabolites will be analyzed using a population PK approach. The 
results from the population PK analyses will be presented in a 
separate report. 

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Patients who consent to PK sampling will take the evening dose the day before Visit 2; the date and time of this dose should be recorded as reported by the 
patient. At Visit 2, patients will be administered the Visit 2 dose of lumateperone at the study site after an overnight fast of at least 10 hours and will continue 
to fast for at least 2 hours after dosing. The date and time of lumateperone administration at Visit 2 must be recorded. PK sampling will be collected at Visit 2 
at predose (within 30 minutes prior to dosing), between 0.5 hour and 1-hour post-dose and between 1.5 hour and 3 hours post-dose. The date and time of PK 
sample collection at each timepoint must be recorded. Patients will be instructed not to take an evening dose of lumateperone at Visit 2. The next dose of 
lumateperone should be taken the next evening as prescribed. ADT should be taken as prescribed throughout the PK sampling period. 
9 
Patients who consent to PK sampling will have one blood sample collected at Visit 7. The patient-reported date and time of lumateperone administration prior 
to PK sampling on the evening before Visit 7 should be recorded. The date and time of PK sample collection must be recorded.  
10 
Antidepressant prescriptions will be provided to patients as needed through the duration of the study. 
 

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2. 
ETHICAL CONSIDERATIONS 
2.1 
Institutional Review Board and Independent Ethics Committee 
Approval by the Institutional Review Board and Independent Ethics Committee (IRB/IEC) is 
required before the start of the study. 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/IEC members. During the 
course of the study, the Investigator will provide timely and accurate reports to the IRB/IEC on 
the progress of the study, at intervals not exceeding 1 year (or as appropriate) and will notify the 
IRB/IEC of serious adverse events (SAEs) or other significant safety findings. The study protocol, 
informed consent form (ICF), information sheet advertisements, and amendments (if any) will be 
approved by the IRBs/IECs at the study centers in conformance with US CFR, Title 21, Part 56 
and applicable local regulations. 
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 and applicable local regulations. 
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 locally applicable regulations shall be obtained from each patient before entering the 
study or performing any study-specific procedure that involves risk to the patient. If the ICF is 
revised during the study, all active participating patients 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 and be allowed to read the approved ICF. After receiving an explanation of study procedures, 
patients will have the opportunity to have any questions answered before signing the ICF. The 
Investigator must address all questions raised by the patient. Each patient will read, assent to an 
understanding of, and sign the ICF or other locally applicable authorization form. Each patient will 
be made aware that he/she may withdraw from the study at any time. 
The Investigator 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. The 
Investigator shall retain the signed original ICF and HIPAA or other locally applicable form. 

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3. 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
A list of Sponsor personnel responsible for study oversight is provided in the Study Reference 
Manual. 

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4. 
INTRODUCTION 
Major depressive disorder (MDD) is a serious psychiatric disorder characterized by the presence 
of one or more major depressive episodes (MDE). Major depressive episodes may begin at any 
age; however, the average age of onset is in the mid-20s. The lifetime risk for MDD is estimated 
at 5% to 12% for men and 10% to 25% for women. Depression can have damaging effects on 
health and wellbeing, and leave one at risk for social withdrawal, alcohol abuse, and disrupted 
work, family, and social life (Kupferberg et al, 2016). MDD has a high mortality rate and up to 
15% of patients with severe major depressive episodes die by suicide. In addition, individuals with 
MDD have high medical morbidity and are often plagued with more pain and physical illness than 
the general population. 
Lumateperone (trade name CAPLYTA®) was approved by the Food and Drug Administration 
(FDA) on December 20, 2019 under NDA 209500 for the treatment of schizophrenia in adults. 
ITI, the Sponsor, is exploring the utility of lumateperone as adjunctive therapy in the treatment of 
MDD. 
Although the mechanism of action is unknown, the efficacy of lumateperone could be mediated 
through a combination of antagonist activity at central serotonin 5-HT2A receptors, serotonin 
reuptake inhibition, and postsynaptic antagonist activity at central dopamine D2 receptors. 
Lumateperone’s indirect glutamatergic modulation via activation of dopamine D1 receptors in 
combination with serotonin reuptake inhibition may also play a role in antidepressant response. 
Importantly, lumateperone lacks potent off-target interactions that have been associated with side 
effects of other antipsychotic drugs. 
Clinical data from 3 well-controlled studies in patients with schizophrenia (Studies ITI-007-005, 
ITI-007-301, and ITI-007-302) are consistent with respect to the pharmacological profile and 
prediction for antidepressant effects with favorable safety and tolerability. In addition to improving 
psychotic symptoms, lumateperone also improved symptoms of depression in patients with 
schizophrenia and comorbid depression at baseline. Similar improvements in depression 
symptoms were also seen in a one-year open label study of lumateperone in patients with 
schizophrenia (ITI-007-303). In this study, the favorable safety and tolerability profile was 
sustained. 
Clinical data from 3 well-controlled bipolar depression studies (Studies ITI-007-401, ITI-007-404, 
and ITI-007-402) demonstrated efficacy in bipolar depression and confirmed lumateperone’s 
tolerability and favorable safety profile. In Study ITI-007-404, once-daily lumateperone 42 mg 
met the primary and key secondary endpoints with statistically significant improvement over 
placebo at Week 6 (study endpoint), as measured by change from baseline in Montgomery-Åsberg 
Depression Rating Scale (MADRS) total score and the Clinical Global Impression Scale, Bipolar 
version, Severity (CGI-BP-S) total score, respectively, and demonstrated statistically significant 
improvement on the CGI-BP-S depression. 
In Study ITI-007-402, once-daily lumateperone 42 mg adjunctive to lithium or valproate met the 
primary and key secondary endpoints with statistically significant improvement over placebo at 
Week 6 (study endpoint), as measured by change from baseline in MADRS total score and the 
CGI-BP-S depression subscale. 

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In Study ITI-007-401, lumateperone did not meet its primary efficacy endpoint. Patients who 
continued in the optional open-label extension of lumateperone 42 mg maintained improvement 
and their depressive symptoms did not worsen. 
Safety data from these studies and other trials with lumateperone, which has been administered to 
more than 3300 individuals for up to one year, show lumateperone to be well tolerated across a 
dose range from 0.7 to 126 mg, with a safety profile similar to placebo.  
The purpose of the current study is to evaluate the safety and tolerability of lumateperone 42 mg 
as adjunctive treatment to antidepressant therapy (ADT) in patients with MDD. More detailed 
information about the known and expected benefits and risks and reasonably expected AEs is 
provided in the current lumateperone Investigator’s Brochure. 

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5. 
STUDY OBJECTIVES 
The primary objective of the Open-label Safety Study is to evaluate the safety and tolerability of 
lumateperone 42 mg administered orally once daily for approximately 26 weeks as adjunctive 
treatment to ADT in patients with MDD. 
The secondary objective of the Open-label Safety Study is to evaluate whether lumateperone 
42 mg administered orally once daily for approximately 26 weeks as adjunctive treatment to ADT 
improves or maintains improvement of depressive symptoms in patients with MDD as measured 
by change from baseline in the MADRS total score and change from baseline in the CGI-S score. 

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6. 
INVESTIGATIONAL PLAN 
6.1 
Overall Study Design and Plan 
Study ITI-007-503 (“Study 503”) is an international, open-label, multicenter, 6-month study to 
assess the safety and tolerability of lumateperone as adjunctive therapy in patients with MDD. The 
Study will be performed at approximately 120 study centers. No de novo patients will be enrolled. 
Patients who have safely completed the lead-in studies may be eligible to participate in this Open-
label Safety Study. Lead-in study completion is defined as a patient who completes the double-
blind treatment period (ie, all scheduled visits up to and including Visit 8) of the lead-in study. 
The study will be conducted as follows: 
• A Screening Period of one day in duration. Potential patients rolling over from the lead-
in studies will be evaluated for eligibility during the Screening/Baseline Visit 
(Visit 1/Day 1) which is the same visit as Visit 8/Day 43 of the lead-in study. Patients who 
meet all eligibility criteria at the Screening/Baseline Visit (Visit 1/Day 1) will be dispensed 
lumateperone 42 mg to be self-administered each evening without respect to food. 
• A 26-week Open-label Treatment Period during which patients will self-administer 
lumateperone, to be taken each evening, without respect to food. Background ADT should 
also continue as previously prescribed, with no change of dose from the lead-in studies. 
Patients will attend visits on Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, and 26. 
The Open-label Treatment Period will last a total of 26 weeks. A patient will be defined as 
a treatment completer if the patient completes the Open-label Treatment Period (all 
scheduled visits up to and including Visit 16/Week 26). 
• A 2-week Safety Follow-up Period. A Safety Follow-up visit will occur approximately 2 
weeks after completion of the Open-label Treatment Period or after the Early Termination 
(ET) Visit. Any ongoing AEs at the Safety Follow-up Visit must be followed until 
resolution, until the AE stabilizes, until it is determined to be not clinically significant, or 
until the patient is lost to follow-up. 
Patients who prematurely discontinue should be seen for an ET visit as soon as possible and will 
also be asked to return to for a Safety Follow-up visit approximately 2 weeks after Visit 16/ET 
visit. 
The maximum per-patient study duration for the Open-label Safety Study will be approximately 
28 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 8.4. 

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6.2 
Scientific Rationale for Study Design 
6.2.1 
Study Design 
Long term maintenance treatment of depression beyond the acute exacerbation of illness is 
standard of care, as MDD is for many patients a chronic, relapsing illness. Therefore, a longer-
term, open label study to undertake safety monitoring and efficacy evaluations for periods greater 
than the time required to treat the symptoms of a depressive episode is warranted. This study allows 
patients who have participated in the double blind lead-in studies to start or continue treatment 
with lumateperone for up to 6 months, which is considered an adequate amount of time to collect 
safety, tolerability, and efficacy data to further the information gained in the acute treatment 
exposures. 
6.2.2 
Dose Selection 
Lumateperone 42 mg was selected for this study was based on preclinical and clinical data, as well 
as the efficacy seen with this dose in bipolar depression studies ITI-007-404 and ITI-007-402. This 
dose delivers full occupancy of the cortical 5-HT2A receptors (>85% occupancy) with modest 
striatal D2 receptor occupancy and SERT occupancy. Data from human PET brain receptor 
occupancy studies with lumateperone indicate that a dose as low as 7 mg is associated with >85% 
occupancy of cortical 5-HT2A receptors, while the 42-mg dose demonstrates approximately 40% 
striatal D2 receptor occupancy. SERT occupancy has been demonstrated to be comparable to D2 
receptor occupancy. Moreover, in patients with schizophrenia and bipolar depression, once-daily 
oral administration of lumateperone 42 mg has been well tolerated with no dose titration needed 
and with a safety profile similar to placebo with up to 6 weeks’ treatment duration. 
6.3 
Study Population 
6.3.1 
Inclusion Criteria 
In addition to the Inclusion Criteria below, patients will be checked for previous participation in 
an ITI-007 clinical study and for duplicate enrollment by study site staff through Verified Clinical 
Trials (VCT). 
 Each patient entering the Open-label Safety Study must meet all of the following criteria:  
1. In the opinion of the Investigator, the patient must have safely completed the lead-in study. 
2. The patient must understand the written informed consent for the Open-label Safety Study, 
provide signed and witnessed written informed consent. 
3. The patient is taking his/her ADT as prescribed from the lead-in study. 
4. The patient must agree to continue using highly effective methods of birth control as 
specified in the lead-in study through the Safety-Follow-up Period of the Open-label Safety 
Study, or female patients or female partners of male patients must be of non-childbearing 
potential. 

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6.3.2 
Exclusion Criteria 
Because all patients enrolled in the lead-in study were required to satisfy exclusion criteria for 
participation in the lead-in study, the Investigator should assess if there has been any change in 
patient health status. Any newly-emergent medical condition reported during the lead-in study 
must be evaluated by the Investigator and should be discussed with the Sponsor or designee before 
enrolling the patient in the study. 
Patients enrolling directly from the lead-in study to the Open-label Safety Study at the 
Screening/Baseline Visit (Visit 1/Day 1) will be excluded if they meet the following criteria: 
1. In the opinion of the Investigator, the patient is unable to comply with study procedures or 
judged to be inappropriate for the study. 
2. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior 
during the course of her/his participation in the study or is considered to be an imminent 
danger to her/himself or others, and/or: 
a. At Visit 1/Day 1, the patient scores “yes” on Suicidal Ideation Items 4 or 5 of the 
C-SSRS “Since Last Visit” version; 
b. At Visit 1/Day 1, the patient scores ≥ 5 on the MADRS Item 10 (Suicidal Thoughts). 
3. 
Based on the Investigator’s clinical judgement, any abnormal clinical laboratory test or 
ECG results obtained throughout the lead-in study that are considered clinically significant 
and preclude safe participation in the study. 
4. 
The patient is breast-feeding or pregnant; female patients of childbearing potential must 
have a negative urine pregnancy test at Visit 1/Day 1. 
5. 
Has a positive urine drug test at Visit 1/Day 1. Positive tests attributable to prescription 
treatments (eg, opioids, benzodiazepines) may not be exclusionary if the use is not chronic 
and is able to be safely discontinued based on Investigator judgment and with the 
concurrence of the Sponsor or designee. 
6. 
The patient has any other condition that may be detrimental to the patient if she/he 
participates in the study. 

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6.4 
Stopping Criteria 
6.4.1 
Discontinuation of Patients from Therapy or Assessment: Patient-level Stopping 
Criteria 
A premature discontinuation will occur when a patient who signed the ICF ceases participation in 
the study, regardless of circumstances, before the completion of all study visits and procedures. 
Patients can be prematurely discontinued from the study for one of the following reasons: 
• Death 
• AE 
• Lack of efficacy (patients whose MDD symptoms worsen or are determined by the 
Investigator to not be adequately controlled prior to completing the open-label treatment 
period may be withdrawn from the study to start appropriate treatment at the Investigator’s 
discretion) 
• Protocol violation 
• Study terminated by Sponsor 
• Site terminated by Sponsor 
• Withdrawal by subject or withdrawal of consent 
• Lost to follow-up 
• Pregnancy 
• Other 
NOTE: If a patient discontinues due to withdrawal of consent and either a concurrent AE was 
reported or concurrent lack of efficacy was documented, 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 discontinue from the study, including patients who discontinue due to lost to follow-
up, and do not return to the study center for final assessments 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 
final assessments at an ET Visit. All patients who prematurely discontinue from the study should 
return for the Safety Follow-up Visit. 
6.4.2 
 Study Stopping Criteria 
This study will be regularly monitored for safety and tolerability based on routine review of safety 
data. On a quarterly basis during study conduct, all open-label safety data (adverse events, clinical 

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laboratory measures, vital signs, ECGs, and C-SSRS) will be reviewed. If the Study Physician 
determines at any point during the open-label treatment period that the risk of study continuation 
outweighs the benefits, a determination to stop the study can occur in conjunction with discussions 
with the Head of Clinical Development or designee, the Head of Drug Safety and 
Pharmacovigilance, and the Chief Medical Officer. 
6.5 
Patient Replacement Procedures 
Patients who prematurely discontinue from the study during the Open-label Treatment Period will 
not 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/IEC and 
competent local authorities (if applicable) and the signature page, signed by the Investigator, has 
been received by the Sponsor. If the protocol is amended to eliminate or reduce the risk to patients, 
the amendment may be implemented before IRB/IEC review and approval. However, the IRB/IEC 
must be informed in writing of such an amendment, and approval must be obtained within 
reasonable time limits. 
Administrative changes, such as changes in study personnel, will be specified in the Study 
Reference Manual. Administrative changes will not require a protocol amendment. 

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7.1.1 
Supply of Lumateperone 
Lumateperone will be provided in treatment cards and shipped under ambient conditions. The 
treatment card for lumateperone will contain one 2 × 5 strip of capsules. Each blister card will 
contain a sufficient quantity of capsules for 1 patient for: 
• 1 week (7 doses, plus 3 extra doses), to be dispensed at every visit through Visit 4/ Week 3; 
• 2 weeks (14 doses, plus 6 extra doses), to be dispensed at every visit beginning with Visit 5/ 
Week 4 through for the duration of the 26-week treatment period. 
7.1.2 
Storage of Lumateperone 
Lumateperone must be stored in a secure area, eg, a locked cabinet, protected from moisture, and 
kept at room temperature. Sites must report any temperature excursions as described in the Study 
Reference Manual or contact the Sponsor or its designee for further instructions. 
7.2 
Adjunctive Background Antidepressant Therapy 
Antidepressant prescriptions will be provided to patients as needed through the duration of the 
study. Background ADT should continue as previously prescribed during the lead-in studies. 
Any modifications to background ADT must be discussed with the Sponsor or designee prior to 
initiation of any changes. 
7.3 
Lumateperone Accountability 
The Investigator will maintain accurate records of receipt of lumateperone, including dates of 
receipt. In addition, accurate records will be kept regarding when and how much lumateperone is 
dispensed and used by each patient in the study. Reasons for deviation from the expected 
dispensing regimen must also be recorded. 
At the end of the study, all lumateperone doses must be accounted for. In addition, at the end of 
the study, all unused lumateperone and empty lumateperone treatment cards should be returned to 
the Sponsor or designee or destroyed, as per instructions provided by the Sponsor. 
7.4 
Method of Assigning Patients to Treatment Groups 
After a patient signs the ICF at Visit 1 of the Open-label Treatment Period, site personnel will 
register the patient in the interactive web response system (IWRS). All rollover patients will be 
identified using the same Patient ID that was assigned by IWRS in the lead-in study. 
Lumateperone will be labeled with medication kit numbers. The IWRS will provide the study 
center with the specific medication kit number(s) for each eligible patient at the time of enrollment. 
Study center personnel will dispense lumateperone according to the IWRS instructions. Study 
center personnel will also log onto the IWRS at subsequent visits to obtain a kit number for 
dispensing lumateperone. Study centers will receive the IWRS confirmation notifications for each 
transaction. All notifications are to be maintained with the study source documents. 

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7.5 
Blinding 
Not applicable. This is an open-label study. 
7.6 
Unblinding 
Not applicable. This is an open-label study. 
7.7 
Monitoring Treatment Compliance 
Medication adherence will be emphasized at every visit. Lumateperone compliance during any 
period will be closely monitored. Compliance is based on the number of capsules prescribed and 
number of capsules taken. At every visit, study staff will count the number of capsules remaining 
in the blister pack. Any irregularities in medication adherence should be discussed with the patient. 
All errors in medication dispensing or administration must be carefully documented. These errors 
may include providing the wrong dose, not taking the dose as prescribed, or losing medication. 
In addition, at every visit, study staff will ask the patient about compliance with prescribed 
background ADT dosing regimen.  
Any exceptions to non-compliance due to unusual circumstances should be discussed with the 
Sponsor or designee. 
7.8 
Prior and Concomitant Medications 
7.8.1 
Prior Medications 
Patients should continue taking her/his ADT from the lead-in study as prescribed. Medication 
history, including the use of psychotropic medication or of any other medication, should be 
recorded at the Screening/Baseline Visit (Visit 1/Day 1). 
7.8.2 
Prohibited Medications 
Use of the following products during the study is prohibited: alcohol, cannabis, illicit drugs, any 
known 5-HT2A receptor antagonist or inverse agonist, any strong cytochrome P450 3A4 inhibitor 
or cytochrome P450 3A4 inducer, or any drugs with known psychotropic properties or any non-
psychotropic drugs with potential central nervous system effects. 
Any positive result on urine drug screen should be discussed with the Sponsor or designee. 

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7.8.3 
Rescue Medications 
Medications for the acute treatment of extrapyramidal symptoms and akathisia are allowed. 
Zolpidem may be taken for insomnia, in the evening at bedtime and prior to midnight for the 
treatment of insomnia. If zolpidem is not available in specific regions, another sedative hypnotic 
may be approved by the Sponsor or designee. 
The date of each dose of rescue medication administration as well as the name and dosage regimen 
of the rescue medication must be recorded on the eCRF. 
7.9 
Treatment after Discontinuation 
Patients whose depressive symptoms worsen or are determined by the Investigator not to be 
adequately controlled prior to completing the Open-label Treatment Period may, at the 
Investigator’s discretion, be discontinued from the Open-label Treatment Period in order to start 
appropriate treatment. This new treatment will not be provided by the Sponsor. Patients who 
initiate a new treatment for depression during the study must be discontinued from the study and 
should also return for the Safety Follow-up visit. 
All patients who prematurely discontinue from the Open-label Treatment Period regardless of 
cause should be seen for a final assessment at the ET Visit. All patients who prematurely 
discontinue from the Open-label Treatment Period should return for the Safety Follow-up visit. 

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8. 
 EFFECTIVENESS, SAFETY, AND OTHER ASSESSMENTS 
8.1 
Effectiveness Assessments 
8.1.1 
Montgomery-Åsberg Depression Rating Scale (MADRS) 
The MADRS is a 10-item scale designed to measure the overall severity of depressive symptoms 
(Montgomery and Åsberg, 1979). Individual items are rated by the Investigator or Sponsor-
approved rater on a scale of 0 to 6 in which a score of 6 represents the most severe symptoms for 
each item assessed. Patients are rated on items assessing feelings of sadness, lassitude, pessimism, 
inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. 
The MADRS total score ranges from 0 to 60. The MADRS will be completed by a Sponsor-
approved rater. 
8.1.2 
Clinical Global Impression-Severity 
The Clinical Global Impression Scale-Severity provides the clinician’s assessment of the overall 
severity of the patients psychopathology (Guy, 1976). The CGI-S asks the clinician: “Considering 
your total clinical experience with this particular population, how mentally ill is the patient at this 
time?” which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline 
mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most 
extremely ill patients. 
The CGI-S will be completed by a trained and Sponsor-approved rater. 
8.2 
Safety 
All patients who receive study drug (ie, lumateperone 42 mg) will be evaluated for safety. Safety 
assessments will include incidence of AEs, C-SSRS assessment for suicidality, EPS assessment as 
measured by AIMS, BARS, and SAS scales, clinical laboratory evaluations, ECG evaluations, 
vital sign measurements, and physical examination and neurological findings. Additional details 
pertaining to safety assessments are provided in the Schedule of Evaluations (Table 1-1). 
8.2.1 
Adverse Events 
8.2.1.1 
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. 

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8.2.1.2 
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 drug 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. 
8.2.1.3 
Classification of Adverse Events and Serious Adverse Events 
8.2.1.3.1 
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 8.2.1.2). 
Severity will be assessed according to the following scale: 
Mild: 
A type of AE 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 AE 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 AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 

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8.2.1.3.2 
Causality Assessment 
For each reported AE and SAE, the Investigator must provide an assessment of causal relationship 
to study drug. Causal relationship must be assessed by answering the following question: 
Is there a reasonable possibility study drug caused the event? 
Yes: 
There is evidence to suggest a causal relationship between study drug and adverse 
event, ie: 
• There is a reasonable temporal relationship between study drug 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 
No: 
There is no evidence to suggest a causal relationship between study drug and adverse 
event, ie: 
• There is no reasonable temporal relationship between study drug and the event, or 
• The patient did not take study drug, 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. 
8.2.1.4 
Time Period and Frequency of AE and SAE Reporting 
 The Investigator will report all AEs from the time informed consent was obtained until the final 
protocol-defined study visit or last known dose date of study drug + 1 day, whichever is later. 
The Investigator will report all SAEs from the time informed consent was obtained until 30 days 
after the last known dose date 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 

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you feel since your last visit?” 
8.2.1.5 
Adverse Event Reporting Procedures 
8.2.1.5.1 
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 8.2.1.2 for the definition of SAEs and Section 
8.2.1.5.2 for SAE reporting procedures. 
• Document all actions taken with regard to study drug. 
• 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. 
8.2.1.5.2 
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 is obtained. Within 24 hours of learning of any AE that meets one of the criteria 
for an SAE, study center personnel must report the event to the Sponsor on the SAE Form. In 
addition to completing the SAE form, the Study Physician may also be notified by telephone. 
If, during follow-up, any nonserious AE worsens and eventually meets any SAE criterion, that AE 
should be recorded as a new SAE. 
Preplanned hospitalizations (eg, elective procedures for pre-existing conditions that did not 
worsen, such as cosmetic surgery and hysterectomy) are excluded from SAE reporting. 
The study center must email or fax the SAE form to the SAE email address below. Even if an 
initial report is made by telephone, the SAE form containing all available details must still be 
emailed or faxed 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. 

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free T3 and T4) will be measured at the Screening/Baseline Visit (Visit 1/Day 1) and Visit 
16/ET only. 
• Urinalysis: macroscopic (pH, specific gravity, glucose, protein, ketones, bilirubin, nitrates, 
blood) and microscopic (red blood cells/high-power field, white blood cells/high-power 
field, casts, epithelial cells, crystals, granulation). 
• Urine Drug Screen (UDS): Urine testing for drugs (eg, amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine metabolites, methadone, opiates, phencyclidine) 
will be performed. 
• Urine and serum pregnancy tests: Female patients who are of childbearing potential 
(FOCBP) will undergo a serum and a urine pregnancy test at Screening/Baseline Visit 
(Visit 1/Day 1). For all other visits, a urine pregnancy test will be performed. Unscheduled 
pregnancy tests may be administered at any time during the study at the Investigator’s 
discretion. 
A central laboratory will be used to evaluate all urine and blood samples, which will be collected, 
processed, and stored according to the instructions provided in the Laboratory Manual. Additional 
information regarding sample shipment is provided in the Laboratory Manual. 
8.2.5 
Vital Signs 
Vital signs (pulse rate, systolic and diastolic blood pressure [BP], body temperature, and body 
weight) will be assessed at every visit during the study as specified in the Schedule of Evaluations 
(Table 1-1). Height and BMI are assessed at the Screening/Baseline Visit (Visit 1/Day 1) only; 
waist circumference will be assessed at Screening/Baseline (Visit 1/Day 1) and Visit 16/ET.  
Blood pressure and pulse rate will be measured twice: once after the patient is resting quietly in 
the supine position followed by once after at least 2 minutes in the standing positions. BP may be 
measured either manually or by machine but using the same method consistently for each patient 
throughout the study. 
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. 
8.2.6 
Electrocardiograms 
A 12-lead ECG will be performed as specified in the Schedule of Evaluations (Table 1-1). Each 
ECG assessment will be conducted after the patient has been resting quietly in the supine position 
and will comprise ten-second epochs from 12-lead ECGs. ECG parameters to be measured include 
HR, QRS, PR, QT, QTcB, QTcF and RR intervals. 

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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. 
8.2.7 
Other Safety Assessments 
8.2.7.1 
Columbia–Suicide Severity Rating Scale 
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and 
behavior (Posner et al, 2011). The C-SSRS will be completed by a trained and Sponsor-approved 
rater. 
 Suicidal ideation is classified on a 5-item scale: 
1. Wish to be dead 
2. Nonspecific active suicidal thoughts 
3. Active suicidal ideation with any methods [not plan] without intent to act 
4. Active suicidal ideation with some intent to act, without specific plan, and 
5. Active suicidal ideation with specific plan and intent. 
The C-SSRS also captures information about the intensity of ideation, specifically the frequency, 
duration, controllability, deterrents, and reasons for the most severe types of ideation. 
Suicidal behavior categories are: 
• Completed suicide 
• Actual attempt 
• Interrupted attempt 
• Aborted attempt, and 
• Preparatory acts or behavior 
More than 1 classification can be selected provided it represents separate episodes. For actual 
attempts only, the actual or potential lethality is classified for the initial, most lethal, and most 
recent attempts. 
The C-SSRS will be completed at all study visits. At Screening/Baseline (Visit 1/Day 1) and at all 
other visits, the C-SSRS will be completed for suicidal ideation and behavior since the previous 
visit (“Since Last Visit” version). Before the patient leaves the study site, the Investigator or 
appropriately qualified designee will assess the patient’s C-SSRS results. 
The patient should not be released from the study center until the results of the C-SSRS are 
reviewed and the patient is not considered to be at risk. If there is doubt about whether a patient is 
at risk, the Investigator must obtain appropriate psychiatric consultation. The results of the C-SSRS 
will be recorded in the eCRF. The C-SSRS will be completed by a trained and Sponsor-approved 
rater. 

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8.2.7.2 
Extrapyramidal Scales 
8.2.7.2.1 
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” 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. There are an 
additional 2 items on dental status that are answered yes or no. The AIMS is to be completed at 
Screening/Baseline (Visit 1/Day 1) and Visits 2, 5, 7, 9, 11, 13, 15, and 16/ET as specified in the 
Schedule of Evaluations (Table 1-1). 
8.2.7.2.2 
Barnes Akathisia Rating Scale 
The BARS is a rating scale for drug-induced akathisia developed by Barnes (1989). It includes the 
rating of observable restless movements, the subjective awareness of restlessness, and the distress 
associated with the akathisia. There is also a global rating for severity. The scale is completed by 
the investigator or an expert site-based rater after a standard examination. Objective akathisia, 
subjective awareness and subjective distress are rated on a 4-point scale from 0 to 3, yielding a 
total score from 0 to 9. The Global Clinical Assessment of Akathisia is rated separately, on a 
6-point scale from 0 to 5. The BARS is to be completed at Screening/Baseline (Visit 1/Day 1) and 
Visits 2, 5, 7, 9, 11, 13, 15, and 16/ET as specified in the Schedule of Evaluations (Table 1-1). 
8.2.7.2.3 
Simpson-Angus Scale 
The SAS is a measure of extrapyramidal side effects (Simpson &Angus, 1970). The SAS is used 
for assessment of antipsychotic-induced parkinsonism in both clinical practice and research 
settings. Ten items including rating gait, arm dropping, shoulder shaking, elbow rigidity, wrist 
rigidity, leg pendulousness, head dropping, glabella tap, tremor, and salivation are rated on a scale 
from 0 (normal) to 4 (extreme in severity). The SAS should be conducted by the investigator or an 
expert site-based rater in a room where the patient can walk a sufficient distance to allow a natural 
pace (eg, 15 paces). Each side of the body should be examined. The SAS is to be completed at 
Screening/Baseline (Visit 1/Day 1) and Visits 2, 5, 7, 9, 11, 13, 15, and 16/ET as specified in the 
Schedule of Evaluations (Table 1-1). 
8.2.7.3 
Physical Examination 
A modified physical examination, including neurological and excluding genital/rectal 
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 
licensed to perform physical examinations. 
8.3 
Pharmacokinetic Assessments 
For patients who consent to PK sampling, blood samples for determination of plasma 
concentrations of lumateperone (IC200056) and metabolites (IC200131, IC200161, IC200565, 
IC201308, and IC201309) will be collected at Visit 2 (Week 1) and Visit 7 (Week 8). 

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• On the evening prior to Visit 2, patients will self-administer lumateperone and record the 
date and time of lumateperone dosing. 
• At Visit 2: 
o 
Patients will arrive at the site after a minimum of 10 hours fasting. 
o 
The site will record the patient-reported date and time of the prior dose of 
lumateperone.  
o 
Patients will receive a dose of lumateperone 42 mg and will continue to fast for at 
least 2 hours postdose. The date and time of the Visit 2 lumateperone dose must also 
be recorded. 
o 
Blood for PK samples will be collected predose (within 30 minutes prior to dosing), 
between 0.5 hour and 1-hour post-dose and between 1.5 hour and 3 hours post-dose. 
The date and time of PK sample collection at each timepoint must be recorded. 
o 
Patients will be instructed not to take an evening dose of lumateperone at Visit 2. 
o 
Patients will be instructed to resume lumateperone dosing as prescribed on the 
following day. 
• At Visit 7: 
o 
The site will record the patient-reported date and time that lumateperone was taken 
on the evening before Visit 7.  
o 
A PK blood sample will be collected. The date and time of PK sample collection 
must be recorded. 
Blood samples for PK analysis will be collected, processed, stored, and shipped as per instructions 
provided in the Laboratory Manual. 

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8.4 
Schedule of Assessments 
The schedule of study procedures and assessments is presented by visit in the Schedules of 
Evaluations (Table 1-1). The descriptions of the procedures to be performed at each visit are 
provided below. Unscheduled visits for repeat study assessments may be performed at for safety 
reasons or at the discretion of the Investigator. 
8.4.1 
 Screening/Baseline Visit (Visit 1/Day 1) 
 Informed consent and HIPAA (or other local authorization where applicable) must be obtained 
from the patient before any study procedures are conducted. The format and content of the ICF 
must have been agreed upon by the Investigator, the appropriate IRB/IEC, and the Sponsor.  
After obtaining written informed consent, the following assessments and procedures are to be 
performed on Day 1 according to the Schedule of Evaluations in Table 1-1. All Screening 
assessments must be performed in person. 
• Review of Inclusion/Exclusion criteria, including a review medical, psychiatric, and 
medication histories. 
• ADT compliance check 
• Physical examination  
• ECG 
• Vital signs (body temperature, blood pressure, and pulse), weight, height, waist 
circumference, and BMI  
• MADRS 
• CGI-S 
• AIMS/BARS/SAS 
• C-SSRS  
• Blood draw and urinalysis (standard clinical labs, drug screening, and pregnancy testing 
for FOCBPs) after an overnight fast of at least 10 hours 
• Review of AEs 
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed. 

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8.4.2 
Open-label Treatment Period 
8.4.2.1 
Visit 2/Week 1 
•  Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 
• Review of concomitant medications 
• ECG  
• Vital signs (body temperature, blood pressure, and pulse) and weight  
• MADRS  
• CGI-S 
• AIMS/BARS/SAS 
• C-SSRS  
• Blood draw and urinalysis (standard clinical labs, drug screening, and pregnancy testing 
for FOCBPs) after an overnight fast of at least 10 hours 
• Patients who consent to PK sampling should be in a fasted state for at least 10 hours prior 
to PK sampling and lumateperone dosing. 
o 
The site will record the patient-reported date and time of the prior evening’s dose of 
lumateperone. 
o 
A PK blood sample will be collected predose (within 30 minutes prior to dosing). 
The date and time of PK sampling must be recorded. 
o 
Lumateperone 42 mg will be administered with approximately 240 mL water under 
fasted condition. The date and time of dosing must be recorded. 
o 
Additional PK blood samples will be collected between 30 mins and 1 hour postdose 
and between 1.5 and 3 hours postdose. The date and times of PK sampling must be 
recorded. 
o 
Patients will continue to fast for at least 2 hours postdose. 
o 
The next dose of lumateperone should be taken the following evening as prescribed. 
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed. 
8.4.2.2 
Visit 3/Week 2 and Visit 4/Week 3 
• Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 

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• Review of concomitant medications 
• Vital signs (body temperature, blood pressure, and pulse) and weight  
• MADRS  
• CGI-S 
• C-SSRS  
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed.  
8.4.2.3 
Visit 5/Week 4, Visit 9/Week 12, Visit 13/Week 20, and Visit 15/Week 24 
• Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 
• Review of concomitant medications 
• Vital signs (body temperature, blood pressure, and pulse) and weight  
• MADRS  
• CGI-S 
• AIMS/BARS/SAS 
• C-SSRS  
• Urine pregnancy testing, for FOCBPs 
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed. 
8.4.2.4 
Visit 6/Week 6, Visit 8/Week 10, Visit 10/Week 14, Visit 12/Week 18, and 
Visit 14/Week 22 
• Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 
• Review of concomitant medications 
• Vital signs (body temperature, blood pressure, and pulse) and weight  
• C-SSRS  
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed 

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8.4.2.5 
Visit 7/Week 8 and Visit 11/Week 16 
• Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 
• Review of concomitant medications 
• ECG  
• Vital signs (body temperature, blood pressure, and pulse) and weight  
• MADRS  
• CGI-S 
• AIMS/BARS/SAS 
• C-SSRS  
• Blood draw and urinalysis (standard clinical labs, drug screening, and pregnancy testing 
for FOCBPs) after an overnight fast of at least 10 hours 
• Visit 7 only: For patients who consent to PK sampling, one blood sample will be 
collected. The date and time of PK sampling must be recorded. 
• Dispense open-label lumateperone 
• Dispense ADT prescription as needed. 
8.4.2.6 
Visit 16/ET/Week 26 
• Lumateperone return and compliance check 
• ADT compliance check 
• Review of AEs 
• Review of concomitant medications 
• Physical examination  
• ECG  
• Vital signs (body temperature, blood pressure, and pulse), weight, and waist circumference 
• MADRS  
• CGI-S 
• AIMS/BARS/SAS 
• C-SSRS  
• Blood draw and urinalysis (standard clinical labs, drug screening, and pregnancy testing 
for FOCBPs) 

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8.4.3 
 Safety Follow-up Visit (Visit 17/Week 28) 
At the Safety Follow-up Visit, the following procedures will be performed: 
• Review of AEs 
• Review of concomitant medications 
• Vital signs (body temperature, blood pressure, and pulse), and weight 
• MADRS 
• C-SSRS. 

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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 important endpoints including primary and key 
secondary endpoints. 
Continuous variables will be summarized using descriptive statistics (number of patients [n], 
mean, standard deviation [SD], median, minimum, and maximum, unless otherwise stated). 
Categorical variables will be summarized using frequency counts and percentages. 
The baseline for each specific efficacy/safety change-from-baseline analysis endpoint is defined 
as the last measurement prior to the first dose of study treatment from the lead-in study. 
9.2 
Determination of Sample Size 
The sample size is not based on statistical power considerations, but is based on the number of 
patients who may be eligible based on participation in the lead-in study. It is expected that the 
majority of patients who safely complete the lead-in study will participate in the 26-week Open-
label Treatment Period. 
9.3 
Analysis Populations 
The following analysis populations will be considered in the statistical analysis of the study: 
• The Enrolled Population includes all patients who sign the informed consent for this Open-
label Safety Study  
• Safety Population includes all patients in the Enrolled Population who receive at least one 
dose of open-label lumateperone 
• PK Population includes all patients in the Safety Population who have at least one 
evaluable PK sample. 
9.4 
Statistical Analyses 
9.4.1 
Patient Disposition 
The number of patients in each study population will be summarized by treatment group and study 
center as follows: 
• The number of patients who were screened will be summarized overall by study center.  
• The number of patients in the Safety Population will be summarized overall. 
In addition, the number and percentage of patients who complete the Open-label Treatment Period 
and who prematurely discontinued from the Open-label Treatment Period will be summarized 
overall and by reasons for premature discontinuation for the Safety Population. 

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9.4.2 
Demographics and Other Baseline Characteristics 
Demographic parameters as allowed by local country legislation (eg, age, sex, race, ethnicity, 
weight, body mass index, etc) and other baseline characteristics will be summarized for the Safety 
Population. 
Prior medical and surgical history will be summarized for the Safety Population. 
Baseline efficacy parameters MADRS total score and CGI-S score will be summarized by for the 
Safety Population. 
• Prior medication is defined as any medication taken before the date of the first dose of 
open-label lumateperone. 
• Prior concomitant medication is any medication that started before the date of the first dose 
of open-label lumateperone and stopped or is ongoing after the date of the first dose of 
open-label lumateperone.  
• Concomitant medication is defined as any medication taken on or after the date of the first 
dose of open-label study drug. 
Prior, prior concomitant, and concomitant medication use will be summarized as the number and 
proportion of patients who received each prior, prior concomitant, and/or concomitant medication 
within each therapeutic class. Multiple medications used by a patient will only be counted once. 
Any medication that was started after the date of the last dose of open-label lumateperone will not 
be included in the summary but will be included in the patient data listings. 
9.4.3 
Extent of Exposure and Treatment Compliance 
9.4.3.1 
Extent of Exposure  
Exposure to lumateperone for the Safety Population will be summarized for treatment duration, 
calculated as the number of days from the date of the first dose of open-label lumateperone taken 
to the date of the last dose taken, inclusive. The number and percentage of patients with each 
treatment duration category will be summarized, respectively. 
9.4.3.2 
Measurement of Treatment Compliance 
Dosing compliance for a specified period is defined as the total number of capsules of 
lumateperone actually taken by a patient during the treatment period divided by the number of 
capsules of lumateperone that is expected to be taken during the Open-label Treatment Period 
multiplied by 100. 
The total number of capsules actually taken during the treatment period will be calculated from 
the study drug record. Descriptive statistics for study drug dosing compliance together with 
compliance category will be summarized for the Safety Population. 

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9.4.4 
Efficacy Analyses 
The efficacy analyses will be based on patients in the Safety Population with an available baseline 
efficacy value and at least one postbaseline efficacy assessment during the Open-label Treatment 
Period.  
The efficacy endpoints are change from baseline in MADRS total score and change from baseline 
in CGI-S score. 
9.4.4.1 
MADRS Total Score 
A descriptive summary for the change from baseline to each assessment visit in MADRS total 
score will be provided. Also, the number of patients who achieved remission (MADRS total score 
≤ 12) will be provided. In addition, the responder rate (response is defined as at least 50% reduction 
in MADRS total score compared to baseline score) will be summarized. 
9.4.4.2 
CGI-S Score 
A descriptive summary for the change from baseline to each assessment visit in CGI-S score will 
be provided. 
9.4.5 
Safety Analyses 
Safety analyses will be performed using the Safety Population. The safety parameters will include 
AEs, clinical laboratory, vital sign, ECGs, BARS, AIMS, SAS, and C-SSRS. 
9.4.5.1 
Adverse Events 
Adverse events will be recorded for each patient from the time informed consent was obtained 
until the final protocol-defined study visit or the last known dose date of lumateperone + 1 day. 
SAEs will be reported from the time informed consent was obtained until 30 days after the last 
known dose date of lumateperone. 
Adverse events will be coded by system organ class (SOC) and preferred term using the Medical 
Dictionary for Regulatory Activities (MedDRA).  
An AE that occurs during the Open-label Treatment Period will be considered a treatment-
emergent AE (TEAE) if it starts as a new event or if its severity increases during the Open-label 
Treatment Period. An AE that occurs more than 1 day after the date of the last dose of open-label 
lumateperone will not be counted as a TEAE. 

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The number and percentage of patients reporting TEAEs will be tabulated by system organ class 
(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 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. 
9.4.5.2 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values (in SI and conventional units) and changes from 
baseline values at each assessment timepoint and at the end of the Open-label Treatment Period 
will be summarized for each clinical laboratory parameter. 
The number and percentage of patients with potentially clinically significant (PCS) postbaseline 
clinical laboratory values during the Open-label Treatment Period will be tabulated for the Safety 
Population. The criteria for PCS laboratory values and details on additional laboratory analyses 
will be provided in the SAP. 
In addition, the number and percentage of patients meeting Hy’s law criteria during the open-label 
treatment period will be provided for the Safety Population. 
9.4.5.3 
Vital Signs 
Descriptive statistics for vital signs (eg, pulse rate, systolic and diastolic blood pressure, body 
weight) and changes from baseline values at each visit, at the end of the treatment period, and at 
the end of the study will be presented for the Safety Population. 
Vital sign values will be considered PCS if they meet both the observed-value and the change-
from-baseline-value criteria. The PCS vital sign criteria will be detailed in the SAP. Details on 
additional vital sign analyses will be provided in the SAP. 
9.4.5.4 
Electrocardiograms 
Descriptive statistics for ECG parameters (eg, ventricular heart rate, QTc interval, QRS interval) 
and changes from baseline values at each assessment timepoint will be summarized for the Safety 
Population.  
The number and percentage of patients with PCS postbaseline ECG values will be summarized for 
the Open-label Treatment Period. The criteria for PCS ECG values and details on additional 
analyses of ECG parameters will be provided in the SAP. 
9.4.5.5 
Other Safety Parameters 
Descriptive statistics for change from baseline to assessment visit and to the end of the Open-label 
Treatment Period in AIMS total score, BARS total score, and SAS total score will be summarized 
based on the Safety Population. 

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9.4.5.5.1 
Columbia Suicide Severity Rating Scale (C-SSRS) 
The number and percentage of patients with suicidality as measured by the C-SSRS will be 
summarized for the Open-label Treatment Period, where suicidality was defined as having at least 
one occurrence of suicidal ideation or at least one occurrence of suicidal behavior. 
The distribution of responses for the most severe suicidal ideation and the most severe suicidal 
behavior will be summarized for lifetime history. 
The distribution of responses for the most severe suicidal ideation and the most severe suicidal 
behavior at baseline and during the Open-label Treatment Period will be summarized. 
Emergence of suicidal ideation, serious suicidal ideation, suicidal behavior, and worsening of 
suicidal ideation (ie, compared with the first dose of study treatment from the lead-in study) during 
the Open-label Treatment Period will be summarized. 
The details of analyses of C-SSRS will be provided in the SAP. 
9.4.6 
Plasma Concentration Parameters 
Individual plasma concentrations of lumateperone and metabolites (IC200131, IC200161, 
IC200565, IC201308, and IC201309) will be listed and summarized by visit/timepoint. 
Plasma concentrations of lumateperone and potentially of selected metabolites will be pooled with 
data from other studies of lumateperone and analyzed using a population PK approach. The results 
from these analyses will be presented in a separate report. 
9.5 
Interim Analysis 
No interim analysis is planned for this study. 
9.6 
Data and Safety Monitoring Board 
Not applicable. 
9.7 
Protocol Deviations 
A deviation from the protocol is an unanticipated departure from the procedures or processes 
approved by the Sponsor and the IRB/IEC 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/IEC should be notified of all major protocol deviations in a timely manner. 

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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, before the start of the study: 
• A completed and signed Form FDA 1572 or equivalent form, if applicable. If, during the 
course of the study, any changes are made that are not reflected on Form FDA 1572 or 
equivalent form, if applicable, a new form must be completed and returned to the Sponsor.  
• A fully executed contract 
• The curricula vitae for the Investigator and all sub-investigators listed on Form FDA 1572 
or equivalent form, 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 or equivalent form, if applicable 
• A copy of the original IRB/IEC 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/IEC 
• A copy of the IRB/IEC-approved ICF 
• A copy of the HIPAA authorization form, or other applicable local privacy forms 
• A list of the IRB/IEC members or the US Department of Health and Human Services 
general assurance number 
• A copy of the laboratory certifications and reference ranges 
• 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 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 number of each patient are 
listed. 
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.  

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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 the patient’s data via a data query will be 
approved by the Investigator prior to final database lock. 
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. 

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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. 
10.4 
Reporting and Publication 
All data generated in this study are the property of the Sponsor. An integrated clinical and 
statistical report will be prepared at the completion of the study. 

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11. 
REFERENCES 
Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry. 1989.154:672-6. 
CAPLYTA [package insert]: New York, NY: Intra-Cellular Therapies, Inc., December 2019. 
caplyta_pi.pdf (intracellulartherapies.com).  
FDA Guidance For Industry: Drug Induced Liver Injury—Pre Marketing Clinical Evaluation, 
July 2009. 
Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. Rockville: US 
Department of Health Education, and Welfare; 1976. 
Kupferberg A, Bicks L, Hasler G. Social functioning in major depressive disorder. Neurosci 
Biobehav R. 2016; 69: 313-332 
Montgomery SA and Åsberg M. A new depression scale designed to be sensitive to change. 
Br J Psychiatry. 1979; 134:382-389. 
Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: initial 
validity and internal consistency findings from three multisite studies with adolescents and 
adults. Am J Psychiatry. 2011;168(12):1266-77. 
Simpson GM. Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiat Scand 
Suppl. 1970; 212:11–9. 

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12. 
APPENDICES 
APPENDIX I. 
ELEMENTS OF INFORMED CONSENT 
Procedures will comply with 21 CFR, Parts 50 and 312. Signed informed consent will be obtained 
for each patient participating in a clinical research study. This 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 or other local health 
authority, the Sponsor, the IRB/IEC, 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/IEC may be required.) 
• For EU countries, the ICF will include a statement of whom to contact, including relevant 
phone and email address, for questions about patient data confidentiality or data breach per 
GDPR. 
• 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 is, or may become, pregnant) that are at present 
unforeseeable 

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• The expected circumstances for which the patient’s participation may be terminated by the 
Investigator without regard to the patient’s consent 
• Any additional costs to the patient that may result from participation in the research 
• The consequences of a patient’s decision to withdraw from the research and procedures for 
an orderly termination of the patient’s participation 
• 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 
• The approximate number of patients involved in the study 
• A statement of permission, providing consent for the patient to participate (eg, “I agree to 
participate . . .”) 
• A place for the patient’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 

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13. 
INVESTIGATOR SIGNATURE PAGE 
I agree to conduct the study in accordance with this Protocol Amendment 1, ITI-007-503, dated 
23 Aug 2021, 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