Intra-Cellular Therapies, Inc. / "A Randomized, Double-blind, Placebo-controlled, Single Site Study to Evaluate the Efficacy of Lumateperone for the Treatment of Major Depressive Disorder (MDD) and Early Life Trauma in Adult Patients Aged 21 to 70 Years
Phase: PHASE4
Conditions: Major Depressive Diorder, Early Life Trauma
Sponsor: University of Texas at Austin

 
IRB TEMPLATE: Standard Protocol Form 
NUMBER 
VERSION DATE 
HRP-UT901 
10/3/2025 
 
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About this Form 
This form is required for research studies that are greater than minimal risk, or minimal risk qualifying for expedited 
review. You can also use this form if you are unsure which review level and/or form is best. 
Additional forms/tools are available for the following: 
• 
Requesting a “Not Human Subjects Research” (NHSR) determination  
• 
Exempt Research requiring only institutional review 
• 
Secondary Use Research where there is no contact with participants 
• 
Non-research treatment protocols (HUDs, EAPs/Compassionate Use, Emergency Use) 
Need help deciding which form to use? Refer to our IRB Template Decision Tree. All protocol templates are available in 
the UTRMS-IRB Library. 
For studies following a sponsor protocol, please use this guidance to assist in your completion of this form.  
Be aware that other institutional requirements outside the scope of IRB review may apply to your research. Please 
see the UT Austin Human Research Navigation Tool for guidance on additional requirements that may apply.  
Instructions for Use 
Do not convert this Word document to PDF.  PDFs block certain review functionality in UTRMS-IRB (such as the ability 
for staff to see system-tracked changes when edits are made) which can hinder review. 
This form uses skip logic. Complete the form in order and answer all questions unless instructed to skip via special 
instructions based on previous responses.  
To fill in a text box, make sure your cursor is within the grey text box before typing or pasting text. Boxes will expand to 
accommodate the full length of text added.  
Once complete, upload this form on the Basic Study Information section of the online application where prompted to 
upload the protocol (typically question 7 or 8 depending on previous responses).  
 
Please do not delete the Index. 
 
Index 
General Study Information  
Consent/Assent Pathways  
Risks & Discomforts 
Study Elements w/ Add’l Requirements 
Add’l Consent Considerations/Disclosures 
Privacy & Confidentiality 
Subject Population 
Compensation & Costs 
Data Sharing & Future Use 
Recruitment & Screening 
Benefits 
Conflicts of Interest 
 

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General Study Information 
 
Study Title: 
 
Neurocircuitry Mechanisms and Efficacy of Lumateperone as Adjunctive Therapy for Major Depressive 
Disorder and History of Early Life Abuse 
 
 
1. Review Type (Choose one) 
 
Please choose which level of review best fits your research. This is an investigator’s assessment of review and does not 
preclude the IRB from alternate determinations. In cases where the investigator and the IRB’s determination of review 
conflict, the IRB’s determination will be considered the official determination.  
 
Note: “Expedited” review does not refer to the timeliness of the review of your protocol, but specific categories of research 
defined by OHRP. If you would like help determining which type of review best fits your research study, please contact the IRB 
staff in the Office of Research Support & Compliance: https://research.utexas.edu/ors/human-subjects/get-help/  
 
Click on the appropriate check box (or double click and type an “X” if using Google Docs): 
 ☒ Full Committee – Greater than Minimal Risk Research 
☐ Single Reviewer – Minimal Risk Research (expedited) 
 
 
 
1a. Notification of UT IRB Fees 
Be aware that the UT IRB may charge fees for certain types of reviews. If your project qualifies for either of the project types 
listed below, check the appropriate box and review our website for more information about IRB fees that may apply. Please 
reach out to irb@austin.utexas.edu if you have questions. 
☒ Industry-sponsored Clinical Trial 
☐ Federally-Funded multisite study for which UT IRB is serving as the single IRB of record (for guidance, see our 
website for Single IRB Reliance) 
 
2. External Time Limitation 
 Generally, the IRB will review applications in the order in which they are received. When possible, the IRB can assign higher 
priority to research with externally-imposed urgency that is beyond the control of the researcher (example: grant deadlines, 
research responding to a sudden or emerging event, etc.).  
Completing this section provides the IRB with information but does not guarantee priority review is possible or that a 
requested deadline can be met. Researchers are encouraged to communicate with the IRB as soon as possible when there is 
an urgent situation (ideally before submitting the IRB application), and we will do our best to accommodate requests, as 
possible: https://research.utexas.edu/ors/human-subjects/get-help/ 
 Are you requesting the IRB consider priority review due to an externally-imposed deadline or time limitation 
affecting this submission? 
 ☐ No 
☒ Yes → If yes, briefly describe the urgency or deadline below, including the reason for it: 
 
  
 
The sponsor has requested expedited review in order to ensure funds are available for this 
project. 
 
  3. Is the research taking place at or using data from any of the following: 
Knowing when UT’s external clinical partners are involved helps inform IRB review and reporting.   
 ☒ None of these    
 ☐ Heath Discovery Labs   
 ☐ Central Health              

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 ☐ CommUnity Care 
 ☐ Ascension locations → Submit a request to the Seton Site Approval Tool (SAT) and upload the confirmation email that states the 
request has been submitted in UTRMS under “Other Documents.” Please note, we do NOT need the final approval letter (you will not 
receive SAT approval until after IRB approval is granted). If you encounter issues or have questions about SAT, please reach out to 
siteapproval@seton.org. 
 
4. Research Hypotheses 
Please describe the research aims and hypotheses in the box below. Note: Procedures will be explained in a separate section 
below. 
 
Aim 1: To assess the efficacy of lumateperone 42 mg administered once daily compared with placebo 
in the treatment of patients with Major Depressive Disorder and early life abuse, as measured by change 
from baseline to end of Week 6 in MADRS total score. 
Aim 2: To assess neurocircuitry encoding of threat and reward learning as predictors of lumateperone 
response and as mechanisms of treatment action, and assess the change from pre-dose to post-dose of 
task-evoked brain activation. 
Aim 3: MADRS response rate (proportion of subjects with an improvement ≥50% in the Baseline 
MADRS total score) at Week 6 of Lumateperone as compared to Placebo. 
Aim 4: MADRS remission rate (proportion of subjects with a MADRS total score ≤10) at Week 6 of 
Lumateperone as compared to Placebo. 
Aim 5: To assess the efficacy of lumateperone 42 mg administered once daily compared with placebo 
in the treatment of patients with Major depressive Disorder and early life abuse, as measured by change 
from baseline to end of Week 6 in Clinical Global Impression-Severity (CGI-S) score. 
 
 
5. Study Background 
Provide the rationale and the scientific or scholarly background for the proposed activity, based on existing literature (or 
clinical knowledge). Describe the gaps in current knowledge that the project is intended to address. 
 
Early life trauma is widely documented as a robust risk factor for development of major depressive 
disorder (MDD), in addition to many other mental health disorders1,2. Further, comorbid history of early 
life trauma among those with MDD predicts worse response to first-line pharmacotherapy for MDD2. 
Among the different types of early life traumas, physical and sexual assault tend to be associated with 
particularly worse outcomes in adulthood3. As such, there is a clear need to develop adjunctive therapies 
for those with MDD and histories of early life abuse in order to mitigate the typical poor clinical 
response seen in this population.  
 
An emerging computational neuroscience literature has demonstrated altered neurocircuitry encoding of 
threat and reward learning as a key mechanism linking early life abuse to worse mental health outcomes 
in adulthood. This emerging computational literature complements and extends the well-established link 
between MDD and poor reward learning and decreased reward sensitivity4–6. Indeed, in a prior study we 
demonstrated that decreased prospective reward representations in the striatum mediated poorer reward 
learning and depression symptoms among individuals with histories of early life physical or sexual 
assault7. We’ve also demonstrated decreased encoding of reward prediction errors among women 
exposed to physical or sexual assault in the striatum and anterior insula8,9, and decreased social reward 
prediction error encoding among adolescent girls who experienced physical or sexual assault. Similarly, 
recent work demonstrated altered integration of threat and reward learning (i.e., approach-avoidance 
conflict) in depression10,11, potentially mediated by altered encoding of reward in the striatum. These 
findings are in line with our prior computational work investigating neurocircuitry mechanisms of 
approach-avoidance conflict demonstrating that biased prospective representations of reward vs threat in 

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the salience network mediates decisions to approach reward vs avoid threat12 and that individuals with 
assault histories demonstrate altered approach-avoidance conflict learning13,14. Overall, the emerging 
literature clearly points to altered computational encoding of threat and reward learning as a mechanism 
underlying development of MDD among those with histories of early life assault.  
 
The neurocircuitry implicated in altered threat and reward learning as mechanisms of risk for MDD 
includes the salience network (dorsal anterior cingulate cortex and anterior insula) and striatum. 
Notably, this neurocircuitry overlaps with dopaminergic and serotonergic pathways targeted by atypical 
antipsychotic medications15,16. As such, altered neurocircuitry encoding of threat and reward learning 
could potentially be predictive of clinical outcomes for adjunctive therapies that target these pathways, 
such as lumateperone. There are two main routes by which these pathways could have clinically 
predictive significance. First, individual differences in neurocircuitry encoding of threat and reward 
learning could operate as markers of who would vs would not benefit from lumateperone adjunctive 
therapy. Second, pre- to post-treatment changes in neurocircuitry encoding of reward and threat learning 
could operate as a mechanism of symptom reduction (e.g., lumateperone induced improvements in 
reward and threat neurocircuitry encoding mediate reductions in depression symptoms). These 
possibilities are not mutually exclusive, and both would have considerable clinical significance for 
enabling precision medicine approaches to the treatment of MDD among early life trauma populations. 
 
6. Design and Methodology 
Provide a brief description of the overall study design or data collection methodologies. Details regarding protocol specific 
research procedures will be discussed in the next section below. 
 
This is a single site investigator initiated randomized, double-blind, placebo controlled, fixed-dose study 
in patients with a primary diagnosis of MDD, a history of early life abuse, and who have an inadequate 
response to on-going SSRI treatment. The study will enroll a total of 50 participants (n=50) with 25 
randomized to treatment and 25 to a placebo, and will be conducted in 3 phases:  
Screening Period - After signing the ICF, an identification number will be assigned to the subject. Prior 
to randomization, all subjects will enter a 2 week-day screening period (Screening) to determine 
eligibility. Eligible subjects must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth 
Edition (DSM-5) criteria for MDD without psychotic features, based on the DIAMOND (Diagnostic 
Interview for Anxiety, Mood, and Other Neuropsychiatric Disorders), with a current major depressive 
episode of at least 8 weeks in duration. They must have had an inadequate response (<50% symptom 
reduction) to an adequate trial of at least 1 antidepressant therapy (ADT) (as determined by 
administering the Massachusetts General Hospital Antidepressant Treatment History Questionnaire 
[ATRQ]) in their current Major Depressive Episode (MDE). During Screening Period (2 weeks) patient 
eligibility will be assessed and a Pre-dose fMRI performed. 
Double-blind Treatment Period - Double-blind Treatment Period (6 weeks) during which all eligible 
patients will be randomized to receive lumateperone 42 mg or placebo in 1:1 ratio. At Baseline (Visit 2), 
patients who continue to meet all eligibility criteria will be randomized to either lumateperone or 
placebo.  
Safety Follow-up Period in which all patients will return to the clinic for a safety follow-up visit 
approximately one week after the last dose of study treatment. All patients will complete a post dose 
MRI  1 week after the 6-week study period is completed.  
• During the Pre-Dose and Post-dose MRI, Participants will undergo standard structural imaging 
as well as functional imaging during computational threat and reward learning tasks. 
Computational neuroimaging approaches will characterize neurocircuitry encoding of 
anticipating and delivery of threat and reward outcomes, enabling testing of predictors of 
lumateperone clinical response and mechanism of treatment action.  

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• Patients who discontinue study drug prior to Week 6 but agree to continue participation in the 
Double-blind Treatment Period (DBTP) should be seen at all subsequent protocol-defined visits 
up to week 6 and should also return for the SFU Visit for post dose MRI. Study drug will no 
longer be dispensed for these patients and the clinical management of these patients will be at 
the discretion of the Investigator. 
• Patients who discontinue study drug prior to Week 6 and do not agree to continue participation 
in the DBTP should be seen for an early termination (ET) Visit as soon as possible and should 
also return for the SFU Visit 1 week after the ET Visit. Study drug will no longer be dispensed 
for these patients and the clinical management of these patients will be at the discretion of the 
Investigator; 
Safety Follow-up Period (1 week) during which all patients will return to the clinic for a safety follow-
up (SFU) Visit approximately one week after the end of DBTP, or ET Visit if the patient does not 
complete the DBTP. 
 
 
 
7. 
Study Procedure Description 
 
Provide a step-by-step narrative of what enrolled participants will be asked to do or allow, and/or how data/specimens will be 
collected and used, such that someone else could replicate the procedures based on this description.  
 
Recruitment and consent procedures will be covered in later sections. The description below should cover all procedures involving 
enrolled subjects or participants (or their data/specimens) from start to finish, in sequential order. Include details of all the 
following, as applicable: 
• 
Research measures/tests/data collection tools that will be used. Upload copies of all surveys, interview guides, 
assessments, questionnaires, and any other data collection tools to UTRMS-IRB in the “Other Attachments” section.      
• 
Research interventions and activities, including all stimuli/tasks/instructions that participants will see, hear, or experience 
as part of their participation. Upload copies of all intervention materials (including videos, audio files, handouts, 
photos, scripts, etc.) to UTRMS-IRB in the “Other Attachments” section.      
• 
Biospecimens that will be collected as part of the research procedures, including the type of specimen, method of 
collection, schedule/frequency of collection. 
• 
Secondary data or specimens that will be obtained, how they are collected and used, from what source(s). 
• 
Total duration of all research activities (i.e. expected time commitment of participants).  
 
Note: if this is a Multi-Site or Collaborative Study include the following:  
• 
This is a “Multi-Site Study that involves more than one site performing ALL aspects of the research procedures as outlined 
above.” OR “This is a Collaborative Study that involves UT Austin researchers working with external researchers who are 
engaged in performing the following study activities (list activities).”  
• 
For assistance with Multi-Site/Collaborative research, review UT Guidance: Submitting Studies Relying on UT IRB, 
download HRP-UT932 Request to Rely Assessment Form from the UTRMS-IRB Library and email 
irbreliance@austin.utexas.edu. 
 
 
This is a single site, randomized, double-blind, placebo-controlled study to evaluate the efficacy of 
lumateperone as an adjunctive treatment of patients with MDD and a history of early childhood abuse. 
During the study subjects currently receiving approved dosing regimen of ADT, who experience an 
inadequate therapeutic response according to MADRS score at Baseline, will be randomized in a 1:1 
ratio to Lumateperone 42mg or placebo, and receive treatment for 6 weeks. The primary efficacy 
analysis will be based on the week 6 assessment of the primary and secondary efficacy endpoints. 
The overall duration of the study, including Screening and intervention period, will be approximately 9 
weeks per subject: a 2-week screening period, 6 weeks of double-blind treatment, and a 1-week safety 
follow-up visit. 
The study design is presented in Figure 1. 
 
Figure 1. 

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The study will be conducted as follows: 
• 
Screening Period (2 weeks): 
o  A 2-week Screening Period during which patient eligibility will be assessed. After obtaining written 
informed consent, diagnostic interviews and physical examinations will be conducted, vital signs and ECGs 
will be assessed, and blood and urine samples will be collected for laboratory assessments. With the 
exception of stable, allowed concomitant medications, patients must discontinue prohibited psychotropic 
drugs during the Screening Period. The following rating scales will be administered. 
Clinician Rater: CAPS-5, MADRS, DIAMOND, SCID-5 Borderline Personality module, CGI-S, MGH-
ATRQ, CSSRS 
PROS, GAD-7, QIDS-SR-16, EQ 5D-5L, CTQ, GASS, PCL-5, NWS, MCI 
Once deemed eligible, the subject will also be offered to enroll in the optional EMA wellness app to be 
completed 3X daily from screening visit to the end of study visit 
• 
Double-blind Treatment Period (DBTP, 6 weeks): 
o At Baseline (Visit 2), patients who continue to meet all eligibility criteria will be 
randomized to 1 of 2 treatment arms, lumateperone 42 mg or matching placebo, and will 
enter the 6-week DBTP. Patients will be administered the first dose of study drug in the 
evening of the Baseline Visit (Visit 2/Day 1). A single dose will be taken each evening, 
with or without food, for the duration of the 6-week DBTP. 
o MRI assessments will be completed at baseline Pre- dose and post dose at 1-week safety 
follow up visit. 
 
1.1.1 
Dose Selection 
Lumateperone capsules are approved in the US by the FDA for the treatment of schizophrenia in adults and 
for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, 
as monotherapy and as adjunctive therapy with lithium or valproate. The recommended dosage regimen is 
lumateperone 42 mg administered orally once daily. Several studies have shown that lumateperone has a 
                                                        
 
                                                                                                                                   
                                                                                                     
 
            
 
 
 
 
           
 
 
 
 
 
                                         
 
Double Blind Treatment Period 
6 Weeks 
Safety Follow up 
1-week post Treatment 
Lumateperone or Placebo 
6 weekly study visits 
Ecological Momentary Assessments (3 times per day) 
PRE-DOSE 
MRI 
POST-DOSE 
MRI 
Screening Period 
2 Weeks 

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favorable safety profile, exhibiting a similar tolerance to placebo, with no significant adverse effects 
reported. The purpose of this study is to determine the efficacy and safety of once daily lumateperone 42 
mg as an adjunctive therapy for the treatment of patients with a history of childhood abuse and MDD. 
Symptoms of depression may or may not improve during participation in this study; half of the patients in 
this study will receive placebo. However, the information obtained from this study may help to treat people 
suffering from MDD with history of childhood abuse. 
2. Study Population 
2.1 
Inclusion Criteria 
To be eligible to participate in the study, patients must meet the following inclusion criteria: 
1. Provide written informed consent before the initiation of any study-specific procedures. See 
informed consent requirements; 
NOTE: Patients who are unable to independently provide informed consent will be ineligible to participate 
in this study. 
2. Male or female, between the ages of 21 and 70 years, inclusive; 
3. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-
5-TR)criteria for MDD without psychotic symptoms, as confirmed by a trained rater using the 
modified Structured Clinical Interview (DIAMOND) for DSM-5,  
4. MADRS total score ≥ 22 at Screening (Visit 1) and Baseline (Visit 2) 
5. Endorse >=1 physical or sexual assault prior to age 16 on the interview-based trauma assessment.  
Many studies refer to early life trauma as prior to age 18. Here we define early life assault as less 
than 16, rather than 18, in order to ensure a clearer separation between early life and adulthood. 
While another option might be to restrict even further (e.g., age of trauma < 10), for feasibility (e.g., 
facilitating recruitment) and generalizability (e.g., results extend to MDD and early life trauma more 
broadly than just early childhood trauma), we decided on physical or sexual assault prior to age 16.  
Regarding the focus on physical or sexual assault, there are two main reasons. First, the definition 
of physical and sexual assault can more easily be operationalized through a behavioral description 
of an event (e.g., has anyone hit you with a fist, has anyone hit you with an object, etc), enabling 
more precise assessment and detection. Second, there is a robustly elevated risk for mood disorders 
following assaultive traumas relative to non-assaultive traumas. As such, there is greater clinical 
need to establish adjunctive treatments among those experiencing assaultive traumas.  
 
6. Participants must have been treated with the same dose of antidepressant therapy for at least 6 weeks, 
with less than 50% improvement, and be committed to stay on the same stable dosing regimen for the 
Screening period and for the entire study, at or above the minimally adequate dose in the ATRQ. 
Documentation of stable and ongoing ADT must be verified by documentation from the subject’s 
psychiatrist, pharmacist, primary care physician, or other qualified healthcare professional. 
7. Females of childbearing potential agree to use at least an acceptable method of birth control 
(including but not limited to hormonal contraception, intrauterine device, vasectomized partner, 
bilateral tubal occlusion, condom with or without spermicide, cap with spermicide, diaphragm with 
spermicide, sponge with spermicide, or double barrier methods) from the time informed consent is 
provided through the end of the SFU period. NOTE: Females of non-childbearing potential (defined 
as either permanently sterilized, or post-menopausal females [defined as at least one year with no 
menses without an alternative medical explanation]) are exempt from the birth control requirement. 
8. Ability to follow study instructions and likely to complete all required visits. 
2.2 
Exclusion Criteria 

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Patients who meet any of the following exclusion criteria will not be eligible to participate in the study. 
Psychiatric Criteria 
1. Has a current primary DSM-5-TR psychiatric diagnosis other than Major depressive disorder. 
These include: 
i. PTSD, OCD, Bipolar Disorder, Schizophrenia, schizoaffective disorder, or other psychotic 
disorders; 
ii. Intellectual disability, Dementia or other cognitive disorders; 
iii. Moderate or severe substance use disorder (excluding for nicotine); 
2. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during the 
course of his/her participation in the study or 
i. At Screening (Visit 1), the patient scores “yes” on Items 4 or 5 in the Suicidal 
Ideation section of the C-SSRS within 6 months prior to Screening; or 
ii. At Screening (Visit 1), the patient has history of suicidal attempt(s) within 1 year 
prior to Screening (Visit 1); or 
iii. At Baseline/randomization (Visit 2), the patient scores “yes” on Items 4 or 5 in the 
Suicidal Ideation section of the C-SSRS since the Screening Visit; or 
iv. At Screening (Visit 1) or Baseline (Visit 2), scores ≥ 4 on Item 10 (suicidal 
thoughts) on the rater administered MADRS; or 
v. Considered to be an imminent danger to himself/herself or others. 
Treatment-related Criteria: 
3. MRI contraindications: History of shrapnel or other metal or electronic implants in the body(such 
as pacemakers, aneurysm clips, ferrous surgical devices, metallic tattoos on the head, etc.). The 
patient has received electroconvulsive therapy (ECT), vagal nerve stimulation, or repetitive 
trans-cranial magnetic stimulation within the past 1 year; 
4. The patient has known hypersensitivity or intolerance to lumateperone, or to any of the excipients; 
5. Treatment with a depot/long-acting injectable antipsychotic within 1 cycle before 
Screening (Visit 1); 
6. The following agents are excluded and must be discontinued at Screening (Visit 1): 
i. Any moderate or strong cytochrome P450 3A4 inhibitor (CYP3A4), or any CYP3A4 
inducer; 
ii. Central opioid agonists/antagonists, including tramadol; 
iii. Anticonvulsants, mood stabilizers, antidepressants, stimulants, antipsychotics, and non-
benzodiazepine anxiolytics; 
iv. Dietary supplements and medical foods unless approved by the Sponsor or designee. Daily 
multivitamin use is permitted; 
7. Monoamine oxidase inhibitors within 14 days prior to Baseline/Randomization (Visit 2); 
8. Other drugs with known psychotropic properties or any non-psychotropic drugs with known or 
potentially significant central nervous system. 
9. The patient plans to initiate psychotherapy or make changes to existing psychotherapy during the 
study (patients who are participating in stable psychotherapy or psychotherapy as a part of their 
treatment are allowed to enroll); 
10. The patient has participated in a previous clinical trial with lumateperone, or has had exposure to 
any investigational product within 6 months of the baseline visit or participated in > 2 clinical studies 

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of an investigational product with a central nervous system indication. 
Other Medical Criteria: 
11. The patient is pregnant or breast-feeding. Female patients of childbearing potential must have a 
negative serum pregnancy test at Screening (Visit 1). On Day 1 (Baseline/Visit 2), female patients 
of childbearing potential must have a negative urine pregnancy test prior to study drug 
administration; 
12. The patient has a positive test for alcohol or drugs of abuse (eg, amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine, methadone, or opioids/opiates) at Screening (Visit 1).  
13. The patient has abnormal laboratory values or clinical findings at Screening (Visit 1) including, but 
not limited to: 
i. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 × the upper 
limit of normal (ULN); 
ii. Total bilirubin > 1.0 × ULN; 
iii. Hemoglobin < 8 g/dL (80 g/L) for females and < 9 g/dL (90 g/L) for males; 
iv. Absolute neutrophil count (ANC) < 1200 cells/μL (1.2 × 109 cells/L); 
v. Thyroid-stimulating hormone (TSH) outside of normal reference range AND free T3 or 
free T4 outside of the reference range. Free T3 and Free T4 will only be evaluated if TSH 
is outside of reference range; 
vi. Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >7.5%, despite 
standard care [> 58 mmol/mol]; 
vii. Positive test for hepatitis B surface antigen and/or hepatitis B core antibody 
immunoglobulin M at screening; positive hepatitis C antibody at Screening (Visit 1), 
with the exception of a patient for whom the reflex HCV RNA test is negative; 
viii. 
Any other clinically significant abnormal laboratory result obtained at screening (Visit 
1); 
14. ECG abnormalities where the patient has corrected QT interval using the Fridericia formula (QTcF) 
> 450 msec for males or > 470 msec for females and/or heart rate < 50 bpm, or evidence of clinically 
significant bundle-branch blocks at Screening (Visit 1); 
15. The patient has any of the following conditions: 
i. Cardiac: uncontrolled angina, or history of a myocardial infarction within 3 months prior to 
screening, or history of a clinically significant cardiac arrhythmia including antipsychotic 
drug-induced corrected QT interval prolongation, or any other cardiac disorder; 
ii. Malignancy: Any diagnosis of cancer (except basal or squamous cell skin carcinoma), 
unless in remission for at least 5 years; 
iii. Gastrointestinal: history of gastric bypass or any other condition that results in 
malabsorption; 
iv. Endocrine: hypo- or hyperthyroidism unless treated and stable with no medication changes 
for at least three months prior to screening, diabetes, unless considered stable with no 
changes in treatment for at least three months prior to screening; 
v. Hepatic: Hepatitis B or Hepatitis C; moderate or severe hepatic impairment (Child-Pugh B 
or C); 
vi. Pulmonary: history of diagnosed and untreated obstructive sleep apnea; 
vii. Neurological: history of epilepsy, seizure or convulsion, or electroencephalogram with 
clinically significant abnormalities, delirium, dementia, amnestic, or central sleep apnea, or 
significant brain trauma, or other cognitive disorder; History of movement disorders. 
viii. 
Infectious: History of human immunodeficiency virus (HIV) infection. 
Note: Any other medical condition, or medical conditions that are stable with treatment (eg, 
hypertension, hypercholesterolemia, or thyroid abnormalities) are allowed as long as the condition 
has been stable for at least 3 months prior to Screening (Visit 1); treatments for these conditions are 
documented, kept stable, and are expected to be unchanged during the study; and the condition is 

Page 10 of 58 
 
not thought to affect safe participation in the study or relevant study outcomes in the opinion of the 
Investigator. 
Other Criteria: 
16. The patient is judged by the Investigator to be inappropriate for the study; 
17. Patient is homeless; 
18. Patient does not speak english; 
2.3 
Rescreening 
 
Individuals who sign the ICF to participate in the study but who do not subsequently meet all the requirements as 
outlined in the inclusion and exclusion criteria and therefore are not randomized (screen failures), may be 
rescreened once, at the discretion of the Principal investigator with the exception of subjects presenting with 
alcohol or drug abuse or previously undisclosed psychoactive drugs; subjects excluded because of QTc 
prolongation or other serious medical conditions at initial screening. 
2.4 
Study Withdrawal or Removal from the Study 
Patients can be prematurely discontinued from the study drug or the study for one of the following reasons: 
• 
Death 
• 
AE 
• 
Lack of efficacy or insufficient therapeutic response 
• 
Lost to follow-up 
• 
Protocol violation 
• 
Study terminated by Investigator 
• 
Withdrawal of consent (by the patient) 
• 
Pregnancy 
• 
Other (such as site closure, administrative reasons, etc) 
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 staff will confirm the primary reason for 
discontinuation and record the primary reason for discontinuation in the subject binder (CRF). 
Patients who discontinue from the study and do not return to the study site for final assessments must be requested 
in writing to return to the site 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 in 
the subject study binder. 
3. Treatment 
3.1 
Study Drug Administration 
Lumateperone 42 mg or matching placebo Capsules will be dispensed at Baseline (Week 1), and weekly 
thereafter until week 5 for oral administration administered once daily. Study drug will be dispensed to 
eligible patients under the supervision of the Investigator or Sub-Investigator, or the designated personnel 
authorized to administer treatment. Study drug should be taken at approximately the same time in the evening, 
with or without food, once daily. 
Table 2. provides formulation information for study drugs. Study drugs will be labeled according to local laws 
and regulations. 
       Table 2. 
Investigational Product 
Lumateperone 42 mg 
Placebo 
Dose frequency 
Once daily in the evening 
Once daily in the evening 
Route 
oral 
oral 
Formulation 
capsule 
capsule 
Appearance 
White opaque hard gelatin capsule 
White opaque hard gelatin capsule 
  

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The study drug will bear the following information: 
• 
Protocol Number or study ID 
• 
Statement indicating that the drug is an investigational drug 
• 
Recommended storage conditions of drug 
• 
Bottle number 
• 
Lot number and date of expiration of the drug 
• 
Quantity of drug per package 
3.1.1 
Storage and Handling of Study Drug 
 All study drug received, will be stored, and handled strictly in accordance with the product label and the site 
standard operating procedures (SOPs). Upon receipt, the study drug will be promptly transferred to the 
environmentally controlled Drug storage area. The research staff will examine the shipment and temperature 
monitoring devices (if applicable) to verify that the study drug was received in acceptable condition. Once 
inspected, the study drug will be stored in a restricted access, secured area with access limited to authorized 
research study staff, under physical conditions consistent with the study drug’s specific requirements. After study 
drug is dispensed to subjects, the remaining study drug will be returned to storage in a restricted access, secured 
area under physical conditions consistent with the study drug’s specific requirements. Study participants will be 
instructed to store the investigational product at room temperature at home, out of the reach of children. 
3.2 
Study Drug Accountability 
The Investigator and designated study staff will maintain accurate records of receipt of all study drugs, including 
dates of receipt.  The study staff will enter the lot number and expiration date on the  Master IP accountability log. 
In addition, accurate records will be kept regarding when and how much study drug is dispensed and used by each 
patient in the study. Reasons for departure from the expected dispensing regimen will be recorded. 
3.3 
Method of Assigning Patients to Treatment Groups 
After a patient signs the ICF at Screening (Visit 1), The investigator will randomly assign a study drug kit number 
for dispensing the study drug. The Kit number, expiration date will be noted on the individual IP dispensing log. 
3.4 
Blinding 
The study will be performed in a double-blind manner. All study drugs will be supplied in identical treatment 
cards and packaging, and will be similar in color, smell, taste, and appearance, thereby enabling double-blind 
conditions. 
3.5 
Unblinding 
Unblinding will be done only in an emergency that requires the study drug to be identified for the medical 
management of the patient. The Investigator will notify the Sponsor or designee immediately and a full written 
explanation must be provided if the blind is broken. Breaking the blinding code will immediately disqualify the 
patient from further participation in the study. 
Treatment codes may be broken by Drug Safety for regulatory reporting purposes. In such cases, the study center 
staff will be kept blinded and the patient will not need to be disqualified from the study. 
3.6 
Monitoring Treatment Compliance 
Study drug adherence will be emphasized at every visit. Study drug compliance during the DBTP will be closely 
monitored.  The study staff will count the number of capsules remaining and compliance will be assessed based 
on the number of capsules prescribed and the number of capsules taken. Every effort will be made to collect 
unused study drug that has been dispensed to the patient., Any irregularities in study drug adherence should be 
discussed with the patient at every visit. Non-compliance is defined as taking less than 80% or more than 120% of 
study drug during any visit to visit evaluation period. Discontinuation for non-compliance will be at the 
Investigator’s discretion and will to be recorded on the subject CRF. All errors in study drug dispensing or 
administration will be carefully documented in the subject study binder. 
3.7 
Prior and Concomitant Medications and Therapies 
All medications taken and therapies received within 6 months prior to Screening must be noted on the eCRF. 
Medications taken and therapies received related to the primary indication (MDD) within the 5 years prior to 
Screening will also be recorded on the Concomitant medication CRF. The reported concomitant medications 
and/or therapies will be reviewed and evaluated by the Investigator to determine if they affect a subject’s 
eligibility or continued participation in the study. 

Page 12 of 58 
 
Medications for the acute treatment of extrapyramidal symptoms and akathisia are allowed, but should not be 
administered within 8 hours prior to movement disorder assessments. 
Zolpidem may be taken for insomnia, in the evening at bedtime and prior to midnight, but no more than 3 times 
per week during the Screening Period and the first 2 weeks of the DBTP only for the treatment of insomnia. 
Lorazepam (or other benzodiazepines) may be taken for anxiety, agitation, irritability, hostility, and restlessness. 
Daily doses should not exceed 3.0 mg/day during the Screening Period and through the first week of the DBTP. 
From Week 2 to week 6 daily dose should not exceed 2 mg/day. Doses may not be given on a standing basis, and 
the lowest effective dose should be used. 
Zolpidem or lorazepam, or their equivalents, should not administered within 8 hours prior to efficacy assessments. 
Any medication or therapy that is taken by or administered to the subject during the course of the study must be 
recorded in the ConMed CRF. The entry must include the dose, regimen, route, indication, and dates of use. 
All medications and other treatments taken by the subject during the study, including those treatments initiated 
before the start of the study, must be recorded on the ConMed CRF. 
3.7.1 
Prohibited Medications 
Use of the following products during the study is prohibited: any known 5-HT2A receptor antagonist or 
inverse agonist, any moderate or strong CYP3A4 inhibitor or any CYP3A4 inducer, or any drugs with known 
psychotropic properties other than those listed in Section 6.7 or any non-psychotropic drugs with potential 
central nervous system effects. 
3.8 
Treatment After Discontinuation of Study Drug or from the Study 
 
Patients whose MDD symptoms worsen or are determined by the Investigator not to be adequately controlled 
prior to completing the DBTP may be discontinued from the DBTP in order to start appropriate treatment at the 
Investigator’s discretion. The Investigator will refer the study subject to their provider for new treatment and will 
not be provide the treatment themselves. Patients who initiate a new treatment during the study must be 
discontinued from the study drug. 
Patients who discontinue study drug prior to Week 6 but agree to continue participation in the Double-blind 
Treatment Period (DBTP) should be seen at all subsequent protocol-defined visits up to week 6 and should also 
return for the SFU Visit. Study drug will no longer be dispensed for these patients and the clinical management 
of these patients will be at the discretion of the Investigator; 
Patients who discontinue study drug prior to Week 6 and do not agree to continue participation in the DBTP 
should be seen for an early termination (ET) Visit as soon as possible and should also return for the SFU Visit 
1 week after the ET Visit. Study drug will no longer be dispensed for these patients. 
3.9 
Contraceptive Precautions 
WOCBP (women of childbearing potential; not surgically sterilized and between menarche and 1-year post-
menopause) must agree to use at least 1 highly effective method of contraception from Screening through at 
Safety follow up one week after the last study drug administration. Women who are not of childbearing potential 
must be congenitally or surgically sterile (hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy, 
as determined by the subject’s medical history) or must be post-menopausal. For men with female sexual 
partners of childbearing potential, examples of medically acceptable forms of contraception include vasectomy 
or male condom for subjects, plus an additional method of contraception for their female partners 
Effective methods of contraception are those that have a failure rate of <1% (when implemented consistently 
and correctly) and include: 
• Intrauterine device (IUD) 
• Bilateral tubal ligation, bilateral salpingectomy, or bilateral tubal occlusive procedure  
• Hormonal contraceptives (e.g., oral, patch, or injectable) 

Page 13 of 58 
 
• A double-barrier protection method (e.g., condom, sponge, or vaginal diaphragm with spermicide cream, foam, 
or gel) 
• Abstinence from heterosexual intercourse is accepted if this is the subject’s usual lifestyle and must be continued 
until at least 2 months after the last dose of study drug. 
Women who are lactating are prohibited from participating in the study. 
 
4. Study Procedures 
Table 1. outlines the timing of procedures and assessments to be performed throughout the study. 
   
    Table 1. 
Study Phase 
Screening 
Period 
Double-blind Treatment Period 
Safety 
Follow-
up 
Period 
Visit Number 
1 
(Screening) 
2 
(Baseline) 
3 
4 
5 
6 
7 
8/ET2 
Study Week 
Week -2 
Week 1 
Week 2 Week 3 Week 4 Week 5 Week 
6 
Week 7 
Study Day 
Up to 15 days 
prior to 
baseline 
 
(± 2 days) 
  
 
Informed 
consent 
X 
I/E criteria 
X 
X 
Medical history 
and 
demographics 
X 
Physical 
examination 
X 
 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
 
X 
Clinical laboratory tests 
Hematology 
X 
 
 
X 
 
 
X 
X 
Biochemistry 
X 
 
 
 
X 
Urinalysis 
(Dipstick) 
X 
X 
 
 
TSH 
X 
 
X 
 
 
 
X 
Hepatitis 
serology 
X 
Urine Drug 
Screen and 
Breath Alcohol 
Test 
X 
X 
 
Serum/Urine 
Pregnancy test 
X 
X 
 
Study Assessments 
SCID- 
X 
 
 

Page 14 of 58 
 
Borderline 
personality 
disorder module 
Diamond 
X 
 
 
CAPS-5 
X 
 
 
 
 
 
 
X 
CGI-S 
X 
X 
 
X 
 
X 
 
X 
MCI 
X 
 
 
 
 
 
 
 
MADRS 
X 
X 
X 
X 
X 
X 
X 
X 
C-SSRS 
X 
X 
X 
X 
X 
X 
X 
X 
MGH-ATRQ 
X 
 
 
 
 
 
 
 
GASS 
 
X 
 
X 
 
X 
X 
GAD-7 
QIDS-SR-16, 
EQ 5D-5L 
X 
X 
X 
X 
X 
X 
X 
X 
PCL-5 
 
X 
 
 
X 
 
X 
X 
Trauma 
Questionnaire 
X 
 
 
 
 
 
 
 
CTQ 
X 
 
 
 
 
 
 
 
EMA 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug 
dispensing 
X 
X 
X 
X 
X 
Study drug 
compliance 
X 
X 
X 
X 
fMRI 
 
X 
 
 
 
 
X 
Prior/concomitant 
medication 
X 
Adverse events 
 
4.1 
Informed Consent  
Before performing any study-related procedures, the Investigator (or designee) will obtain signed informed 
consent from the subject. 
In the event that rescreening occurs, the individual is required to sign a new ICF and must be assigned a new 
identification number. 
4.2 
Order of Assessments 
4.2.1 
Screening (Visit-1 Week-2) 
All subjects agreeing to participate in the study must give informed consent by signing the ICF before any study-
related procedures are performed. Screening begins after ICF has been signed and dated by the subject and the 
Investigator or other appropriate site staff. The duration of the Screening will be 2 weeks. 
The following procedures should be performed in order after the ICF is reviewed and signed: 
1. Collection of medical and psychiatric history, concomitant medications and demographic information. 
Physical examination, ECG and pulse oximetry need to be performed, and height, weight, BMI and 
vital signs recorded. 
2. Standardized assessments to include:  
Clinician Rater: CAPS-5, MADRS, DIAMOND, SCID borderline personality module, CGI-S, MGH-
ATRQ, CSSRS 
PROs:, GAD-7, , QIDS-SR-16, EQ 5D-5L, CTQ, PCL-5, NSW, MCI 
3. Collection of urine sample for urinalysis and drug screen analysis.  

Page 15 of 58 
 
4. Blood sample collection to obtain hematology, biochemistry, hepatitis B and C, HIV, TSH and FSH data. 
A serum pregnancy test (b-HCG) is performed at screening for females of childbearing potential. 
5. Breath alcohol test. 
6. EMA wellness app activation 
Subjects that meet all eligibility and inclusion and no exclusion criteria, will undergo Visit 2 (Baseline). 
4.2.2 
Baseline (Visit 2 Week-1) 
Subjects continuing to meet all eligibility and inclusion criteria and no exclusion criteria, will be randomized 
within each group at Baseline to start the study treatment.   
1. Assessment scales: MADRS, CGI-S C-SSRS, HAMD-17, GAD-7, PHQ-9, QIDS-SR-16, and EQ 5D-5L. 
2. Vital signs, including body temperature, systolic and diastolic BP, HR, pulse oximetry, and RR measures 
after the subject has been resting for at least 3 minutes.  
3. ECGs taken pre-dose.  
4. fMRI will be obtained. 
5. EMA wellness App 
6. AE if applicable 
7. Laboratory tests, consisting of: blood sample for Hematology 
8. POC: Urine drug test, pregnancy test (if applicable) and Breath Alcohol test 
 
4.2.3 
Double-blind Treatment Visits (Visits 3-7 ;Weeks 2-6) 
1. Record AEs as reported by patient or observed by Investigator 
2. Review concomitant medications 
3. Study drug compliance check, return unused Meds at each visit 
4. Vital signs (BP, pulse rate, body temperature, respiratory rate) and weight 
5. Assessment Scales: MADRS, CGI-S C-SSRS, HAMD-17, GAD-7, PHQ-9, QIDS-SR-16, EQ 5D-5L and 
GASS 
6. Lab tests for Hematology for CBC will be completed at wee4 and week6 visits and Complete BW similar to 
screening visit will be completed at Week-7 
7. EMA Wellness App (Optional) 
7.2.4 
Safety Follow up (Visit 8: Week 7) 
1. Record AEs as reported by patient or observed by Investigator 
2. Review concomitant medications 
3. Study drug compliance check, return unused Meds 
4. Vital signs (BP, pulse rate, body temperature, respiratory rate) and weight 
5. fMRI Assessments. 
 
7.3 
Entry Criteria Measurements 
7.3.1 
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) 
The CAPS-5 is a 30-item, clinician-administered assessment tool used to diagnose and measure the severity of 
post-traumatic stress disorder (PTSD) according to the DSM-5 criteria. Administered by a trained study staff.17 
7.3.2 
Diagnostic Interview for Anxiety, Mood, and other Disorders (DIAMOND) 
The Diamond is a semi-structured interview guide to ensure consistency with the DSM 5 diagnostic classification. 
It is administered by a clinician or trained mental health professional who is familiar with the DSM-5 
classification and diagnostic criteria. It provides diagnostic information, including severity, or many DSM-5 
disorders, including MDD. 18 
7.3.3 
Antidepressant Treatment Response Questionnaire (ATRQ) 
The ATRQ examines the efficacy and adequacy of any antidepressant treatment in a step-by-step procedure. This 
widely accepted questionnaire evaluates improvement (0% to 100%) and adequacy (adequate duration and dose) 
19  
7.3.4. SCID-5  Borderline Personality Disorder Module.  
The SCID-5 borderline personality disorder module is a semi-structured interview for BPD to ensure consistency 
with DSM-5 criteria. It is administered by a clinician or trained mental health professional who is familiar with 
the DSM-5 classification and diagnostic criteria.20 

Page 16 of 58 
 
 
7.4 
Efficacy Assessments 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed throughout the study 
and their timing. For assessment scales performed at each visit, MADRS must be the first assessment performed 
by the rater at the site. Subsequent assessments, following MADRS, can be conducted in any order as determined 
by the investigator’s discretion. The following order of assessments is recommended, from the least to the most 
invasive procedure: all assessment scales, vital signs, ECGs and lastly blood draw as indicated in Table 1. 
7.4.1 
 Primary Efficacy Assessment -Montgomery-Åsberg Depression Rating Scale (MADRS) 
The MADRS is a 10-item questionnaire with each item scored between 0 and 6, resulting in a total score between 
0 and 60, with scores above 34 indicating severe depression. Higher MADRS scores indicate more severe 
depression. The questionnaire is most frequently used in clinical studies to measure outcomes in antidepressant 
efficacy studies. This scale exhibits construct validity (internal homogeneity) and the concepts of endogenous and 
non-endogenous depression. The questionnaire includes questions on the following symptoms: (1) apparent 
sadness; (2) reported sadness; (3) inner tension; (4) reduced sleep; (5) reduced appetite; (6) concentration 
difficulties; (7) lassitude; (8) inability to feel; (9) pessimistic thoughts; (10) suicidal thoughts. The MADRS must 
be administered using the Structured Interview Guide for the MADRS (SIGMA).  The MADRS total score at 
screening is a major inclusion criterion of the study, as well as the primary outcome measure for the study. The 
MADRS will be administered at Screening and Baseline and subsequent weekly visits.21  
 
7.4.2 
Secondary Efficacy Assessment-Clinical Global Impression of Severity (CGI-S) 
The CGI-S measures the severity of the disease using a 7-point Likert scale ranging from 1=normal, not at all ill 
to 7=among the most extremely ill subjects22 
 
7.4.3 Ecological Momentary Assessment. Using EMA Wellness software, participants will complete a daily 
assessment of mood and anxiety as well as positive and negative affectivity ratings twice daily.  
Specific assessments of mood and anxiety include: PHQ-9; GAD-7. Specific assessment of positive and 
negative affect: happy, sad, anxious, relaxed. Participants start EMA assessment during two-week run-in period. 
QOL assessment once a week will also occur.  
 
7.5 
Columbia–Suicide Severity Rating Scale 
The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and 
behavior 23The C-SSRS will be completed by a trained and approved rater. The C-SSRS will be 
completed at all study visits. At Screening (Visit 1), the C-SSRS will be completed for the patient’s 
lifetime history of suicidal ideation and behavior (“Baseline/Screening” version). At all other visits, 
the C-SSRS will be completed for suicidal ideation and behavior since the previous visit (“Since Last 
Visit” version). 
7.6 
Extrapyramidal Symptom Assessment 
Glasgow Antipsychotic symptom scale: The Glasgow Antipsychotic Side-effect Scale is a 
patient self-report scale used to screen for antipsychotic side effects.24 
 
7.7 
Vital Signs 
Vital signs (systolic and diastolic blood pressure [BP], pulse rate, respiratory rate, and body temperature) will 
be assessed at every visit during the study as specified in the Schedule of Assessments (Table 1.) 
Blood pressure and pulse rate will be measured in both the supine and standing positions with measurements 
performed after at least 5 minutes lying down and then at least 3 minutes after rising from the supine position 
to the standing position. BP may be measured using the same method consistently for each patient throughout 
the study. 

Page 17 of 58 
 
Body weight, and height will be assessed as specified in the Schedule of Assessments (Table 1.)  
7.8 
Electrocardiogram 
A 12-lead ECG will be performed as specified in the Schedule of assessments (Table 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. 
 
8. Clinical Laboratory Assessments 
Blood and urine samples for clinical laboratory tests will be collected as specified in the Schedule of Evaluations 
Table 4. If possible, patients should fast for at least 8 hours before the collection of clinical laboratory blood tests. 
During Screening, the Investigator/sub-investigator will assess the clinical significance of any values that are 
outside the reference ranges provided by the central laboratory. Patients with abnormal screening laboratory 
results judged to be clinically significant will be excluded from the study. 
Laboratory results will be reviewed by the Investigator/Sub-Investigator throughout the study. The following 
clinical laboratory levels will be measured: 
• 
Hematology: hematocrit; hemoglobin; HbA1c (at Screening [Visit 1] only); red blood cell count with indices 
(mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration); 
reticulocytes; white blood cell count and differential (neutrophils, absolute neutrophil count, lymphocytes, 
monocytes, eosinophils, and basophils) reported as percent (%) and absolute values; and platelet count. 
• 
Chemistry: albumin; ALP; ALT; AST; bilirubin (total, direct); blood urea nitrogen; calcium; chloride; 
cholesterol (total; high-density lipoprotein [HDL] and low-density lipoprotein [LDL] will be calculated and 
reported); creatinine; creatine phosphokinase; gamma-glutamyl transferase; glucose; insulin; lactate 
dehydrogenase; phosphate; potassium; prolactin; sodium; triglycerides; total protein; uric acid. TSH (reflex 
free T3 and free T4) will be measured at Screening (Visit 1) and Visit 7 (Week-6)/ET only. 
• 
Urinalysis: macroscopic (pH, specific gravity, glucose, protein, ketones, bilirubin, nitrites, 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 drug tests for amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine, methadone, or opioids/opiates will be performed Screening 
(Visit 1) and Visit 6 (Day 22)/ET. 
• 
Alcohol Testing: An alcohol test (urine or breath) will be performed at Screening (Visit 1) and Visit 7 
(Week-6)/ET. 
• 
Urine and serum pregnancy tests: Female patients who are of childbearing potential will undergo a serum 
pregnancy test at Screening (Visit 1), and a urine pregnancy test at Baseline (Visit 2/Week 1). 
Unscheduled serum/urine pregnancy tests may be administered at any time at the discretion of the 
Investigator. Serum pregnancy testing will be performed using blood collected as part of protocol-
specified sample; urine pregnancy testing will use a urine dipstick. 
• 
Hepatitis screening: Blood samples will be collected at Screening (Visit 1) from all patients in order to 
perform serology testing for hepatitis B and hepatitis C.  
Table 4. 
Hematology 
Serum Chemistry 
Urinalysis (Dipstick)* (onsite) 

Page 18 of 58 
 
hemoglobin  
hematocrit 
erythrocytes 
platelets 
leukocytes with differential 
(including eosinophils, neutrophils, 
basophils, 
lymphocytes and monocytes)  
  
eGFR (screening only) 
HbA1c (Screening only) 
creatinine 
total bilirubin (and fractionation of 
bilirubin >ULN)  
albumin 
blood urea nitrogen 
total protein 
alkaline phosphatase 
aspartate aminotransferase 
alanine aminotransferase 
glucose 
sodium 
potassium 
magnesium 
calcium 
chloride 
phosphate 
bicarbonate 
TSH (Screening only) 
pH 
specific gravity 
protein 
glucose 
ketones 
bilirubin 
occult blood 
nitrite 
urobilinogen 
leukocyte esterase 
 
* Reflex microscopy when indicated 
 
Pregnancy testing: A serum FSH test will be conducted for all females at Screening. A urine pregnancy test, and serum 
pregnancy test (b-HCG) will be conducted on all WOCBP at Screening. Negative pregnancy test results are required for 
enrollment in the study; a negative urine pregnancy test will be required at Baseline (Week 1) for confirmation.  
Urine drug and alcohol screen at Screening and Baseline: Drug and alcohol abuse testing will be performed according to 
the assessment schedule. Screening for drugs will include: tetrahydrocannabinol, opiates (including oxycodone), 
amphetamines, cocaine, and benzodiazepines. 
Serologic testing for hepatitis B surface antigens, hepatitis C antibodies, and HIV antibody testing will be performed at the 
Screening visit. 
9. Adverse Events 
The Investigator and research study staff will responsible for the detection, documentation, classification, 
reporting, and follow-up of events meeting the definition of an AE or SAE. Procedures for managing AEs and 
SAEs are detailed in the research site’s SOPs. 
 
9.1 Adverse Event Definition 
An AE is any untoward medical occurrence in a study subject administered a pharmaceutical product and may 
not necessarily have a causal relationship with the administered treatment. An AE can therefore be any 
unfavorable and unintended sign (including a clinically significant laboratory abnormality, for example), 
symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of 
its relationship to the medicinal (investigational) product. During the study, an AE can also occur outside the 
time that the study drug(s) was given (e.g., during the time from discontinuation of prohibited medications). 
Preexisting conditions, diseases, or disorders are not considered AEs unless there is a change in severity, 
frequency, or quality. 
 
9.2 Serious Adverse Events and Serious Unexpected Adverse Events 
An SAE is any untoward medical occurrence that at any dose 
• 
Results in death, 
• 
Is life-threatening (at the time of the event), 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization, 
• 
Results in persistent or significant disability/incapacity, or 
• 
Is a congenital anomaly/birth defect. 

Page 19 of 58 
 
 
9.3 Adverse Event Reporting Procedures 
9.3.1 
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 subject’s AE log whether or not they are considered 
causally related to study drug. 
For every AE, the Investigator must: 
9.3.1.1 Provide an assessment of the seriousness of the event (ie, is it an SAE?), as well as the severity and 
causal relationship to the study drug. 
9.3.1.2 Document all actions taken with regard to study drug; 
9.3.1.3 Detail any other treatment measures taken for the AE. 
Any AEs that are ongoing at the time of the End of 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 last known dose of study drug. 
9.3.2 
Reporting Serious Adverse Events 
The Investigator will inform the Sponsor ( ITI) and 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, the study center personnel 
must report the event to the Sponsor on the SAE Report Form. 
If, during follow-up, any nonserious AE worsens and eventually meets the criteria for an SAE, that AE should 
be recorded as a new SAE. 
Table 2. describes the Classification of Adverse Event Causality and Table 3. Outlines the Outcomes of AEs 
or SAEs 
  Table2. 
Classification 
Definition 
Unrelated 
The AE or SAE is judged to be clearly and incontrovertibly due only to extraneous 
causes (e.g., disease, environment) and does not meet the criteria for study drug 
relationship listed under probable, possible, or unlikely. 
Unlikely 
The AE or SAE is unlikely related to the study drug, when the AE or SAE: 
• 
Does not follow a reasonable temporal sequence from administration of the 
study drug. 
• 
May readily have been produced by the subject’s clinical state, environmental 
or toxic factors, or other modes of therapy administered to the subject. 
• 
Does not follow a known pattern of response to the study drug. 
• 
Does not reappear or worsen when the study drug is re-administered. 
Possible 
The AE or SAE is possibly related to the study drug when the connection to the 
study drug appears unlikely but cannot be ruled out with certainty. This causal 
relationship is assigned when the AE or SAE: 
• 
Follows a reasonable temporal sequence from administration of the study 
drug. 
• 
May have been produced by the subject’s clinical state, environmental or toxic 
factors, or other modes of therapy administered to the subject. 

Page 20 of 58 
 
Probable 
The AE or SAE is probably related to the study drug when the connection to study 
drug can be made with a high degree of certainty. This causal relationship is 
assigned when the AE or SAE: 
• 
Follows a reasonable temporal sequence from administration of the study 
drug. 
• 
Cannot be reasonably explained by the known characteristics of the subject’s 
clinical state, environmental or toxic factors, or other modes of therapy 
administered to the subject. 
• 
Disappears or decreases upon cessation or reduction in dose (note that there 
are important exceptions when an AE or SAE does not disappear upon 
discontinuation of the study drug, yet drug relatedness clearly exists e.g., bone 
marrow depression or tardive dyskinesia). 
• 
Follows a known pattern of response to the suspected study drug. 
Definite 
The AE or SAE is definitely related to the study drug when the event: 
• 
Follows a reasonable temporal sequence from administration of the study drug. 
• 
Follows a known pattern of response to the suspected study drug. 
• 
Is confirmed by improvement on stopping and reappearance of the event on 
repeated exposure to the study drug. 
• 
Cannot be reasonably explained by the known characteristics of the subject’s 
clinical state. 
 
 
 
Table 3. 
Classification 
Definition 
Fatal 
The study subject died. 
Resolved 
The AE or SAE has ended. 
Resolved with Sequelae 
The AE or SAE has ended but changes are noted from Baseline. 
Unresolved 
The AE has not ended. 
An AE outcome can only be categorized as unresolved if the AE is: 
• 
Ongoing at the end of the reporting period (i.e., 30 days after the last dose 
of study drug), and the Investigator deems that further follow-up is not 
medically required. 
• 
Lost to follow-up after repeated unsuccessful attempts to contact the 
subject. 
• 
Ongoing and referred to the subject’s physician or a specialist for 
follow-up. 
Reporting Procedure: 
SAE Reporting E-mail: clinicalsafety@propharmagroup.com  
SAE Reporting Fax Number: +1 (866) 681-1063 
Medical Emergency Contact numbers: 
 

Page 21 of 58 
 
Americas (North and South America)/APAC 
      +1 (973) 659-6677 (Primary) 
+1 (512) 652-0191 (Alternate) 
 
10. Neuroimaging procedures.  
 
Whole brain fMRI will be acquired using a 3T Siemens Vida MRI scanner with a 64-channel head coil at the 
Biomedical Imaging Center at the University of Texas at Austin. A high-resolution T1-weighted structural volume 
(256x256x192, 1-mm3 resolution) will be acquired for coregistration and normalization. Functional images will be 
collected using an adapted version of the ABCD project protocol used in our Biomedical Imaging Center, 
enabling both high temporal (TR=786ms) and spatial (2.4mm isotropic voxels) resolution, using a 32 channel 
head coil. We use fMRIPREP to preprocess the data. Standard preprocessing steps will occur prior to within-
subject and between-subject analyses. 
 
Approach-Avoidance Learning Task. Participants are instructed to learn, through trial-and-error, which of three 
responses, indicated with distinct stimuli, to select to achieve a particular outcome. Critically, each response option 
is associated with a probability of both a reward outcome (points) and an aversive outcome (i.e., a mild electric 
shock). Consistent with reinforcement tasks, the response-outcome contingencies (e.g., which option is most likely 
to lead to reward) switch throughout the task, such that half the time the option that is most likely to lead to reward 
is also most likely to lead to a shock, and half the time the highest reward option is least likely to lead to shock. 
Thus, the task systematically manipulates congruency and conflict between reward-threat outcomes and additionally 
introduces a reversal learning61,147 probe for both reward and threat. To motivate adherence to instructions, 
participants are told they will receive monetary compensation in proportion to how well they perform. In contrast 
to fear conditioning tasks that instruct participants to select a shock intensity that nears painful (7/10 Likert scale), 
we would have participants select a level that is annoying and mildly uncomfortable (5/10) to enable tolerance of 
repeated stimulations, as the number of shocks delivered could be higher than during standard conditioning tasks. 
There would be 150 trials of the task. Each initial cue is presented until the participant makes a selection, followed 
by a jittered anticipation phase (2-4s), and then the threat outcome (mild electric shock) and reward outcome (points) 
would be presented sequentially and separated by a jittered ITI of 3-6s. Given that outcomes are driven 
probabilistically following participant choices, the total number of shocks delivered can vary.  
 
 
8. Data Analysis 
Describe the data analysis plan, including any statistical procedures or power analysis. 
 
11. Statistical Analysis 
11.2 Statistical And Analytic Plan 
The primary efficacy endpoint is the change from baseline to end of Week 6(EOT) in MADRS total score. Based 
on the primary hypothetical estimand strategy which assumes patients are on study drug up to the primary time 
point (end of Week 6), MADRS assessments collected off-treatment (ie, efficacy assessment performed more 
than 3 days after last dose of study drug) and/or after starting new treatment for MDD will be set to missing 
(except those collected for patients discontinued due to and will not be included in the primary analysis). The 
missing data in patients who discontinued due to lack of efficacy (LOE) or due to taking non-study treatment for 
MDD will be assumed missing-not-at-random. The missing data in patients who discontinued due to other 
reasons will be assumed as missing- at-random. Missing data will be imputed accordingly to recent 
recommendations using the ‘mice’ package in R. 25,26 
 
The primary analysis will use a mixed-effects model for repeated measures (MMRM) to analyze the change from 
baseline to end of Week 6 in MADRS total score. Similar MMRM models will be used for secondary endpoints. 
An additional analysis will examine slopes of MADRS scores over the 6 week period, testing the hypothesis that 
the active drug group will have a steeper slope of MADRS over the 6 week period. Additional models will test for 
non-linear patterns of change as well. Similar analyses will be conducted on secondary outcomes (e.g. CGI, PTSD 

Page 22 of 58 
 
symptom severity, etc.).  
 
For imaging data, following standard preprocessing, beta coefficients of voxelwise brain activity will be defined 
using standard general linear models. These coefficients will be used in multivariate pattern analysis (MVPA) to 
build classifiers, using support vector machines (SVM), of reward and threat using leave-one-out cross-validation 
and quantify reward and threat anticipation during the task. MVPA classifier output will be analyzed using mixed 
effects models. Threat and reward anticipation as predictors of treatment outcome will be analyzed by including 
these variables as a predictor in the MMRM described above. Threat and reward anticipation as targets of treatment 
will be analyzed in mixed effects model with post-treatment classifier output as the dependent measure and 
including predictors of drug group and including pre-treatment classifier output as a covariate. 
 
11.3 Primary Endpoint Estimand 
The primary efficacy endpoint is the absolute change in MADRS total scores from Baseline to end of 
Treatment visit at Week 6 in subjects on ADT plus Lumateperone or matching placebo. 
The main estimand for the primary efficacy endpoint is defined as follows: 
• 
Target population(TP):Total Population: All randomized participants with MDD and history of early life 
abuse (Baseline MADRS score ≥22) as defined by the study inclusion/exclusion criteria who are randomized 
and dosed  
• 
Variable: Change from Baseline to Week 6 in the MADRS total scores (Visit 7)  
Intercurrent events (ICE) 
1. Study or treatment discontinuation 
a. Due to lack of efficacy 
b. Due to adverse event related to study medication 
c. Due to adverse event unrelated to study medication 
d. Due to other reasons 
2. Treatment with prohibited medication 
3. Death 
a. Related to MDD 
b. Unrelated to MDD 
• 
ICE strategy 
o 
ICE 1a, 1b, 2: A hypothetical strategy will be applied assuming that patients after the ICE follow the 
course of patients receiving placebo. 
o 
ICE 1c, 1d, 3b: A hypothetical strategy will be applied assuming that patients after the ICE follow the 
course of the arm they were randomized to. 
o 
ICE 3a: A composite strategy will be applied by imputing values after the ICE with the worst possible 
MADRS score (=60). 
10.2Secondary  Endpoint Estimand: The key secondary efficacy endpoint is the change from baseline to end 
of Week 6 in the CGI-S score. 
11.4  Efficacy Estimand Analysis 
Main estimands are defined for the primary efficacy variable: 
• 
Absolute change from Baseline to Week 6 of the MADRS total score  
and for the following 3 key secondary efficacy variables in hierarchical rank order of the hypothesis testing 
procedure: 
• 
MADRS response rate (proportion of subjects with an improvement ≥50% in the Baseline MADRS total 
score) at End of Treatment (EOT) Week 6, Lumateperone as compared to placebo 
• 
MADRS remission rate (proportion of subjects with a MADRS total score ≤10) EOT Week 6, 
Lumateperone as compared to placebo 
• 
Change from Baseline to EOT Week -6 in the Clinical Global Impression of Severity (CGI-S) score, 
Lumateperone as compared to placebo 
Confirmatory testing will be performed only for these main estimands, whereby the testing of the key 
secondary estimands will follow the ordered hierarchical approach. 
The primary statistical analysis of all confirmatory tested estimands will be performed on the Total 
Population, using the mixed-effect model repeated measure (MMRM) analysis. For the main primary 
estimand, the changes from baseline in MADRS total score will be analyzed using a Mixed Model with 

Page 23 of 58 
 
Repeated Measures (MMRM). This model will include Treatment, Visit, Treatment-by-Visit interaction and 
the number of failed prior treatments (1 or more than 1) as fixed effects, Baseline value as a covariate, and 
Visit as the repeated effect. The estimated means for each arm as well as the estimated treatment effect 
(Lumateperone – Placebo) along with the 95% confidence intervals for the treatment effect will be presented 
for each visit. The primary estimand will be estimated as the difference between treatment means (MMRM 
least-squares) at the EOT Week 6 (Visit 7).   
As a sensitivity analysis for all estimands, the MMRM analysis will be performed using a range of missing 
value imputations. For the main estimand of the primary efficacy, a tipping point analysis will be applied to 
investigate the robustness of the analysis results.  
 
 
Study Elements Requiring Additional Information or Approvals 
9.   Public Registration and Reporting Requirements  
 
Federal regulations, policy, and some journal guidelines require public registration and results reporting for studies that 
meet the definition of a clinical trial.  
 
Note that the various definitions of “clinical trial” subject to these requirements can be quite broad and include things like 
behavioral interventions conducted outside of traditional healthcare settings.  
 
Answer the following questions and review the linked guidance to see if any of these requirements apply to this study. 
 
 
9a. Does this study involve prospectively assigning participants, or groups of participants, to one or more 
research intervention(s)? 
Intervention includes both physical procedures by which data/specimens are gathered and manipulation of the participant 
or the participant’s environment for research purposes. Can include control groups.  
☐ No → Skip to item 10 
☒ Yes 
 
9b. Is the intention of the study to evaluate the effect of a research intervention on health-related 
biomedical or behavioral outcomes? 
☐ No → Skip to item 10 
☒ Yes 
 
9c. If yes to the above, go to UT Guidance on Clinical Trials Registration and Results Reporting and review 
requirements that may be applicable and select which of the following apply to this study: 
☐ Intended to be submitted for publication in a journal subject to International Committee of Medical Journal 
Editors (ICMJE) requirements 
☐ NIH-funded Clinical Trial (be sure list funding on the Study Funding section of the UTRMS application) 
☒ FDA-defined Applicable Clinical Trial 
☐ Intended to have routine clinical trial costs covered by the Center for Medicare and Medicaid Services (CMS) 
☐ Registration is required per the terms of the award/funding agency 
☐ Meets none of the above requirements but will register voluntarily 
☐ None of the above 
 
9d. Will the UT Austin study team register this study on ClinicalTrials.gov? 
Click here for information on how to identify the “Responsible Party” for registration.  
☒ Yes 
☐ No – This is a multi-site study and the UT PI is not the Responsible Party for registration. The external 
Responsible Party is aware of their duty to register the study.  

Page 24 of 58 
 
☐ No – This study involves an IND or IDE held by someone other than the UT PI, the IND/IDE holder is the 
Responsible Party and is aware of their duty to register the study. 
☐ No – This study meets none of the requirements in item 9c above and the study team prefers not to register 
 
9e. Attest that all relevant reporting requirements for the study will be followed as applicable (regardless of 
ClinicalTrials.gov registration).  
Use the linked guidance in item 9c and review the section titled “Reporting Results” for guidance. This box must be checked 
to confirm you have reviewed the requirements, even if you determine no reporting requirements apply to you. 
☒ Confirm 
 
10. Does the research involve biospecimens of any kind (e.g. blood, tissue, saliva, etc.), biohazards, 
recombinant DNA, or gene transfer?  
☐  No → Skip to item 11 
☒  Yes   
 
10a. Does the research involve human embryonic, human induced pluripotent, or human totipotent stem 
cells; or human gametes or embryos?  
☒  No  
☐  Yes → Be aware that additional review criteria may apply, see UT IRB Policies & Procedures section 18 for guidance.   
 
10b. Will biospecimens be used and stored at UT? 
☒  No, biospecimens collected will be stored at an external site that has responsibility for biosafety  
☐  Yes → UT Institutional Biosafety Committee (IBC) approval is needed. Provide the UT IBC number in the text box 
below: 
 
 
 
 
 
 
 
 
10c. Does the research involve prospective collection of blood from participants? 
☐  No → Skip to item 11 
☒  Yes   
 
10d. Select all methods that will be used to collect blood samples: 
Note that procedures for all forms of specimen collection should be described in the Study Procedures section above. The 
IRB requires the following specific details for blood collection to determine the appropriate review level. 
 
☐ Research sample collected at the same time as non-research blood collection (i.e. extra blood collected)         
☒ Individual needle stick(s)    
☐ Indwelling catheter placed solely for this study  
☐ Accessing indwelling catheter placed for non-research purposes     
☐ Other, specify in text box below: 
 
 
 
 
 
10e. Specify the timing and frequency of blood collection and the volume of blood obtained at each 
collection: 
 
Blood will be collected four times during the study; the total amount of blood each draw is two tubes, 
1 tube that is 9 mL of blood and another that is 8.5 mL. Reference the study procedures chart as well 
as the clinical assessments section for frequency. 
 

Page 25 of 58 
 
 
11. Does the research involve genetic testing/analysis? 
This may include research involving identification and location of specific genes, study of gene products, inherited human 
traits, or identification and analysis of DNA mutations. 
☒  No → Skip to item 12 
☐  Yes   
 
11a. Describe the genetic testing/analysis involved in this study:  
If this is already described earlier in the form (such in the Study Procedures or Data Analysis items), please reference the 
appropriate sections where this can be found in the box below. 
 
 
 
 
 
 
 
 
 
11b. Are participants able to opt-out of or withdraw from the genetic testing part of the research while 
continuing with other parts of the research? 
Be sure this response aligns with language included in the consent form(s). 
☐  Yes  
☐  No   
 
 
 
 
11c. Will or might genetic testing/analysis reveal clinically relevant findings for participants? 
For example, medical conditions that could be treated or information about paternity/lineage. 
☐  No → Skip to item 12 
☐  Yes → Describe potential findings below:  
 
 
 
 
 
 
 
11d. Describe the procedures for providing clinically relevant genetic results to participants: 
Include whether or not genetic counseling will be offered to participants. Specify whether or not participants will be offered 
the option to decline learning the results, or if any results will not be provided (and if so, why). Be sure this response aligns 
with language provided in the consent form(s). 
 
 
 
 
 
 
 
 
11e. Will genetic tests be run in a CLIA-certified laboratory? 
☐  Yes  
☐  No → If no, explain below why this is not necessary:   
 
 
 
 
 
12. For this study, will the researchers obtain, use, or disclose Protected Health Information (PHI) 
regulated under the Health Insurance Portability and Accountability Act (HIPAA)? 
This typically applies to research involving access to medical records. This does not include self-reported health information 
disclosed as part of research surveys/interviews. Guidance on HIPAA protected PHI is available here.   
☐  No → Skip to item 13 

Page 26 of 58 
 
☒  Yes   
 
12a. Select all HIPAA-covered entities providing PHI: 
☒ UT Health Austin                                      ☐ Ascension Seton/other Ascension locations*     
☐ UT Austin University Health Services   ☐ Dell Children’s Medical Center*                         
☐ CommUnity Care                                      ☐ Central Health 
 
☒ Other, specify: 
Clinical Pathologies Laboratory, Biomedical 
Imaging Center 
 
 
*For studies obtaining data from Ascension facilities, please submit a request to the Seton Site Approval Tool (SAT) and upload the confirmation email that 
states the request has been submitted in UTRMS under “Other Documents.” Please note, we do NOT need the final approval letter (you will not receive SAT 
approval until after IRB approval is granted). If you encounter issues or have questions about SAT, please reach out to siteapproval@seton.org. 
 
12b. List the data points or attach a list of the data to be collected about each subject from their medical 
records or other HIPAA protected data source(s). Select one of the following: 
☐ This list is uploaded to UTRMS on the Local Site Documents page under “Other Attachments” 
☒ All data points listed in the text box below: 
 
 
 
 
Medical History will be self-reported by the participant, as listed in the protocol. The 
following will be collected as participation in this study:  
• Lab & Pathology Results  
• MRI Imaging 
 
 
12c. Select all pathways for obtaining HIPAA authorization for accessing PHI for this research: 
NOTE: If obtaining authorization from Ascension patients, use of Ascension’s stand-alone HIPAA authorization form is 
required and this form should be uploaded on the Local Site Documents page in UTRMS under “Other Attachments.” 
Otherwise, non-Ascension HIPAA authorization may be combined with Informed Consent using the HIPAA template 
language embedded within the 920 Standard Consent Template. All UT Austin IRB templates are available in the Templates 
tab of the UTRMS-IRB Library.  
 
☒ Obtaining HIPAA authorization from participants to access PHI → Skip to item 13 if only this box is checked  
☐ Requesting full waiver of participant authorization  
☐ Requesting partial waiver of authorization to access PHI for screening or recruitment only 
All of the following must be checked to qualify for a partial waiver for screening or recruitment: 
☐ Attest that PHI will be accessed ONLY to identify eligible subjects for recruitment in this research. Continued 
access to PHI will be limited to those who later volunteer for the study and provide written authorization. 
☐ Attest that PHI will be accessed only by individuals who have authorization to access the records outside of the 
research context. 
☐ Attest that researchers will not move or transmit identifiable PHI from the covered entity (i.e. the institution 
holding the records, such as the clinic).  
 
12d. Complete the following if requesting a full or partial waiver of HIPAA authorization: 
 
I. 
Specify the date range of records that will be accessed: 
 
 
 
Start date (month/year): 
 
 
 
 
End date (month/year): 
 
 
 
 
II. 
Provide a justification for why the research could not practically be conducted without access to 
PHI and the waiver of patient authorization requested: 

Page 27 of 58 
 
 
☐ Identification/recruitment: – access to records is needed to identify eligible subjects (e.g., chart 
reviews, partial waiver for recruitment, etc.) 
☐  Large number of subjects projected – potential subject population includes a large number of 
records to review and it is not feasible to attempt contact with all subjects 
☐  Outdated records – This is a retrospective study involving subjects who may have moved or expired and 
researchers cannot feasibly attempt to contact required sample 
☐ Total population required - The nature of the research is such that findings will not be valid, or will be 
significantly skewed, if the total eligible population is not included.  
----------------- 
Select all that apply above OR provide different justification below. 
☐ None of the above; specify other justification: 
Note that inconvenience or limited time/resources alone are not sufficient justifications for waiving a patient’s 
right to authorize disclosure of their PHI.  
 
 
 
 
 
 
 
 
III. 
Attest that the protected health information will not be reused or disclosed to any other person 
or entity, except as required by law, for authorized oversight of the research study, or for other 
research where the use or disclosure of the PHI meets IRB and HIPAA requirements.  
This box must be checked.  
             ☐ Confirm 
 
IV. 
The HIPAA regulation requires reasonable efforts to limit protected health information to the 
minimum necessary to accomplish the intended purpose of the use, disclosure or request.  Review 
the linked guidance and attest below that you are obtaining only the minimum information 
necessary to complete the waived activities: 
This box must be checked.  
☐ Confirm 
 
V. 
Provide any additional information you’d like the IRB to consider for why/how all the listed data 
points in item 12b are necessary to answer the research question and comply with the minimum 
necessary requirement described above (if none, this can be left blank):   
 
 
 
 
13. Does this study involve Deception and/or Incomplete Disclosure?  
See IRB Policies and Procedures Section 15 for a description of deception. 
Deception (as applies to research) means intentionally giving research subjects false information in order to establish false 
beliefs during the course of a research study. 
Incomplete disclosure means that the investigator withholds some information about the real purpose of the study or the 
nature of the research procedures.  
☒ No → skip to item 14 
☐ Yes → Note that an alteration of informed consent may need to be requested in the Consent Pathways section. Please 
address items below: 

Page 28 of 58 
 
 
 
13a. Describe the nature of deception/incomplete disclosure and why it is necessary to conduct the 
research. 
 
 
 
 
 
 
 
13b. Will participants be debriefed (i.e. provided additional pertinent information about the nature of the 
deception/incomplete disclosure) after research activities are completed? 
☐ Yes  
☐ No → provide a strong justification below for why this will not occur, then skip to item 14: 
 
 
 
 
 
 
 
 
 
13c. Describe debriefing procedures. 
NOTE: Upload the debriefing form to UTRMS-IRB in the “Local Site Documents” section.  
 
 
 
 
 
 
 
13d. Will research participants have the opportunity to withdraw their data during/after debriefing? 
☐ Yes → Be sure to include language about this option in the uploaded debriefing script.  
☐ No → Provide a strong justification below for why this will not occur: 
 
 
 
 
14. Research Activities Requiring Supplemental Forms or Additional Oversight 
 
Select each of the items below that are relevant to your 
research.  If none apply, this section can be left blank. 
For each item selected, complete and upload the associated 
Supplemental Form in UTRMS-IRB under “Other Attachments” 
or review the linked guidance and follow instructions as 
applicable. 
☒ Investigational Drugs, Biologics, Supplements, or 
other regulated non-device products 
UT Supplement 906 – Investigational Drugs, Biologics, 
and Non-Devices  
☐ Investigational Device 
UT Supplement 905 - Investigational Device  
☐ International Research  
This includes research conducted outside the US, direct 
remote interactions with international participants (i.e. Zoom 
interviews), and research that will collect identifiable data 
from international participants (including online surveys). 
UT Supplement 908 - International Research 
☐ Department of Defense (DoD) 
This includes all research involving DoD funding, facilities, 
data, or personnel (i.e. active military personnel are 
targeted/discernible in the data collected). See Policies & 
Procedures section 25.1 for guidance on DoD applicability. 
UT Supplement 911 - Department of Defense 

Page 29 of 58 
 
 
Subject Population 
 
 
 
☐ Energy introduced to the subject (electrical, 
magnetic, light)  
 
☐ Radiation exposure without direct clinical benefit  
For research involving these activities, be aware that the IRB 
may solicit ancillary review from the UT Austin Environmental 
Health & Safety (EHS) office. Any additional requirements may 
be communicated during review. Guidance on EHS policies and 
reviews is available here: IRB-ML101-Guidance for Institutional 
Reviews and Approvals of Human Research at UT Austin (PDF). 
☐ Use of Artificial Intelligence (AI) in research 
 
As part of UT ISO’s mission and with the growing use of AI in 
research, all research that involves use of AI should be in 
alignment with ISO’s Acceptable Use of AI Policy.  
If your AI platform use is not listed or in alignment with the 
policy above, contact UT ISO at security@utexas.edu prior to 
conducting any research with that AI tool. It is strongly 
recommended to confirm acceptability prior to submitting to 
the IRB. 
15. Sample Size  
Enter the maximum total anticipated sample size, including a breakdown of target sample size per participant group (if 
more than one). Note that the IRB is looking for the number of individual human subjects you plan to enroll. 
 
50 Participants Total: 25 enrolled in a placebo group and 25 enrolled into the treatment group 
 
Participants are those who have MDD and history of early life trauma. 
 
Refer to inclusion/exclusion criteria for detailed list of criteria necessary to meet enrollment. 
 
 16. Sample size rationale 
Describe your sample size rational below.  
 
Sample size is chosen to have moderate statistical power and still ensure feasibility for study 
completion.  
 
17. Research Participant Information 
Describe the general characteristics of the subject populations or groups including gender, health status, and any other 
relevant characteristics. If you have multiple research populations (e.g. teachers and students), clearly outline 
characteristics for each group. 
  
Male and Female inpatient, who have Major Depressive Disorder MDD and history of early life trauma 
who have an inadequate response to on-going SSRI treatment 
 
18. Age range (minimum and maximum) 
Include the age range for target population. If there is no maximum age, this can be noted, but a minimum age required for 
inclusion must be explicitly stated. If you have multiple research populations, clearly state the age range for each group.  

Page 30 of 58 
 
21-70 years old inclusive 
 
 
20. Inclusion/Exclusion Criteria 
Describe the specific criteria that will be used to decide who will be included in and excluded from the research from the 
population of interested or potential subjects. Define technical terms in lay language, as applicable. 
To be eligible to participate in the study, patients must meet the following inclusion criteria: 
9. Provide written informed consent before the initiation of any study-specific procedures. See for 
informed consent requirements; 
NOTE: Patients who are unable to independently provide informed consent will be ineligible to 
participate in this study. 
10. Male or female, between the ages of 21 and 70 years, inclusive; 
11. Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-
5-TR)criteria for MDD without psychotic symptoms, as confirmed by a trained rater using the 
modified Structured Clinical Interview (DIAMOND) for DSM-5,  
12. MADRS total score ≥ 22 at Screening (Visit 1) and Baseline (Visit 2) 
13. Endorse >=1 physical or sexual assault prior to age 16 on the NSW.  
Many studies refer to early life trauma as prior to age 18. Here we define early life assault as less 
than 16, rather than 18, in order to ensure a clearer separation between early life and adulthood. 
While another option might be to restrict even further (e.g., age of trauma < 10), for feasibility 
(e.g., facilitating recruitment) and generalizability (e.g., results extend to MDD and early life 
trauma more broadly than just early childhood trauma), we decided on physical or sexual assault 
prior to age 16.  
Regarding the focus on physical or sexual assault, there are two main reasons. First, the definition 
of physical and sexual assault can more easily be operationalized through a behavioral description 
of an event (e.g., has anyone hit you with a fist, has anyone hit you with an object, etc), enabling 
more precise assessment and detection. Second, there is a robustly elevated risk for mood disorders 
following assaultive traumas relative to non-assaultive traumas. As such, there is greater clinical 
need to establish adjunctive treatments among those experiencing assaultive traumas.  
 
14. Participants must have been treated with the same dose of antidepressant therapy for at least 6 weeks, 
with less than 50% improvement, and be committed to on the same stable dosing regimen for the 
Screening period and for the entire study, at or above the minimally adequate dose in the ATRQ. 
Documentation of stable and ongoing ADT must be verified by documentation from the subject’s 
psychiatrist, pharmacist, primary care physician or other qualified healthcare professional. 
15. Female of childbearing potential and agrees to use at least an acceptable method of birth control 
(including but not limited to hormonal contraception, intrauterine device, vasectomized partner, 
bilateral tubal occlusion, condom with or without spermicide, cap with spermicide, diaphragm with 
spermicide, sponge with spermicide, or double barrier methods) from the time informed consent is 
provided through the end of the SFU period. NOTE: Females of non-childbearing potential (defined 
as either permanently sterilized, or post-menopausal females [defined as at least one year with no 
menses without an alternative medical explanation]) are exempt from the birth control requirement. 
16. Ability to follow study instructions and likely to complete all required visits. 
4.3 
Exclusion Criteria 

Page 31 of 58 
 
Patients who meet any of the following exclusion criteria will not be eligible to participate in the study. 
Psychiatric Criteria 
19. Has a current primary DSM-5-TR psychiatric diagnosis other than Major depressive disorder. 
These include: 
i. PTSD, OCD, Bipolar Disorder, Schizophrenia, schizoaffective disorder, or other psychotic 
disorders; 
ii. Intellectual disability, Dementia or other cognitive disorders; 
iii. Moderate or severe substance use disorder (excluding for nicotine); 
20. In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during 
the course of his/her participation in the study or 
i. At Screening (Visit 1), the patient scores “yes” on Items 4 or 5 in the Suicidal 
Ideation section of the C-SSRS within 6 months prior to Screening; or 
ii. At Screening (Visit 1), the patient has history of suicidal attempt(s) within 1 year 
prior to Screening (Visit 1); or 
iii. At Baseline/randomization (Visit 2), the patient scores “yes” on Items 4 or 5 in the 
Suicidal Ideation section of the C-SSRS since the Screening Visit; or 
iv. At Screening (Visit 1) or Baseline (Visit 2), scores ≥ 4 on Item 10 (suicidal 
thoughts) on the rater administered MADRS; or 
v. Considered to be an imminent danger to himself/herself or others. 
Treatment-related Criteria: 
21. MRI contraindications :History of shrapnel or other metal or electronic implants in the body(such 
as pacemakers, aneurysm clips, ferrous surgical devices, metallic tattoos on the head, etc.)The 
patient has received electroconvulsive therapy (ECT), vagal nerve stimulation, or repetitive 
trans-cranial magnetic stimulation within the past 1 year; 
22. The patient has known hypersensitivity or intolerance to lumateperone, or to any of the 
excipients; 
23. Treatment with a depot/long-acting injectable antipsychotic within 1 cycle before 
Screening (Visit 1); 
24. The following agents are excluded and must be discontinued at Screening (Visit 1): 
i. Any moderate or strong cytochrome P450 3A4 inhibitor (CYP3A4), or any CYP3A4 
inducer; 
ii. Central opioid agonists/antagonists, including tramadol; 
iii. Anticonvulsants, mood stabilizers, antidepressants, stimulants, antipsychotics, and non-
benzodiazepine anxiolytics; 
iv. Dietary supplements and medical foods unless approved by the Sponsor or designee. Daily 
multivitamin use is permitted; 
25. Monoamine oxidase inhibitors within 14 days prior to Baseline/Randomization (Visit 2); 
26. Other drugs with known psychotropic properties or any non-psychotropic drugs with known or 
potentially significant central nervous system. 
27. The patient plans to initiate psychotherapy or make changes to existing psychotherapy during the 
study (patients who are participating in stable psychotherapy or psychotherapy as a part of their 
treatment are allowed to enroll); 
28. The patient has participated in a previous clinical trial with lumateperone, or has had exposure to 

Page 32 of 58 
 
any investigational product within 6 months of the baseline visit or participated in > 2 clinical studies 
of an investigational product with a central nervous system indication. 
Other Medical Criteria: 
29. The patient is pregnant or breast-feeding. Female patients of childbearing potential must have a 
negative serum pregnancy test at Screening (Visit 1). On Day 1 (Baseline/Visit 2), female patients 
of childbearing potential must have a negative urine pregnancy test prior to study drug 
administration; 
30. The patient has a positive test for alcohol or drugs of abuse (eg, amphetamines, barbiturates, 
benzodiazepines, cannabinoids, cocaine, methadone, or opioids/opiates) at Screening (Visit 1).  
31. The patient has abnormal laboratory values or clinical findings at Screening (Visit 1) including, 
but not limited to: 
i. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 × the upper 
limit of normal (ULN); 
ii. Total bilirubin > 1.0 × ULN; 
iii. Hemoglobin < 8 g/dL (80 g/L) for females and < 9 g/dL (90 g/L) for males; 
iv. Absolute neutrophil count (ANC) < 1200 cells/μL (1.2 × 109 cells/L); 
v. Thyroid-stimulating hormone (TSH) outside of normal reference range AND free T3 or 
free T4 outside of the reference range. Free T3 and Free T4 will only be evaluated if TSH 
is outside of reference range; 
vi. Poorly controlled diabetes as defined by a glycosylated hemoglobin (HbA1c) >7.5%, despite 
standard care [> 58 mmol/mol]; 
vii. Positive test for hepatitis B surface antigen and/or hepatitis B core antibody 
immunoglobulin M at screening; positive hepatitis C antibody at Screening (Visit 1), 
with the exception of a patient for whom the reflex HCV RNA test is negative; 
viii. 
Any other clinically significant abnormal laboratory result obtained at screening (Visit 
1); 
32. ECG abnormalities where the patient has corrected QT interval using the Fridericia formula (QTcF) 
> 450 msec for males or > 470 msec for females and/or heart rate < 50 bpm, or evidence of 
clinically significant bundle-branch blocks at Screening (Visit 1); 
33. The patient has any of the following conditions: 
i. Cardiac: uncontrolled angina, or history of a myocardial infarction within 3 months prior to 
screening, or history of a clinically significant cardiac arrhythmia including antipsychotic 
drug-induced corrected QT interval prolongation, or any other cardiac disorder; 
ii. Malignancy: Any diagnosis of cancer (except basal or squamous cell skin carcinoma), 
unless in remission for at least 5 years; 
iii. Gastrointestinal: history of gastric bypass or any other condition that results in 
malabsorption; 
iv. Endocrine: hypo- or hyperthyroidism unless treated and stable with no medication changes 
for at least three months prior to screening, diabetes, unless considered stable with no 
changes in treatment for at least three months prior to screening; 
v. Hepatic: Hepatitis B or Hepatitis C; moderate or severe hepatic impairment (Child-Pugh 
B or C); 
vi. Pulmonary: history of diagnosed and untreated obstructive sleep apnea; 
vii. Neurological: history of epilepsy, seizure or convulsion, or electroencephalogram with 
clinically significant abnormalities, delirium, dementia, amnestic, or central sleep apnea, 
or significant brain trauma, or other cognitive disorder; History of movement disorders. 
viii. 
Infectious: History of human immunodeficiency virus (HIV) infection. 
Note: Any other medical condition, or medical conditions that are stable with treatment (eg, 
hypertension, hypercholesterolemia, or thyroid abnormalities) are allowed as long as the condition 
has been stable for at least 3 months prior to Screening (Visit 1); treatments for these conditions 

Page 33 of 58 
 
are documented, kept stable, and are expected to be unchanged during the study; and the condition 
is not thought to affect safe participation in the study or relevant study outcomes in the opinion of 
the Investigator. 
Other Criteria: 
34. The patient is judged by the Investigator to be inappropriate for the study; 
35. Patient is homeless; 
36. Patient does not speak English 
 
 
 
22. Justification for Target Population(s) 
If the inclusion/exclusion criteria target or exclude a particular segment of the population(s) relevant to the research topic, 
provide a rationale for why this target population is appropriate to address the research questions. Specific groups should 
not be targeted for research based solely on convenience/availability. 
For example, if only UT students are targeted for research affecting a broader population, explain why this is equitable and 
appropriate for this study. 
Early life trauma is widely documented as a robust risk factor for development of major depressive 
disorder (MDD), in addition to many other mental health disorders1,2. Further, comorbid history of early 
life trauma among those with MDD predicts worse response to first-line pharmacotherapy for MDD2. 
Among the different types of early life traumas, physical and sexual assault tend to be associated with 
particularly worse outcomes in adulthood3. As such, there is a clear need to develop adjunctive 
therapies for those with MDD and histories of early life abuse in order to mitigate the typical poor 
clinical response seen in this population.  
An emerging computational neuroscience literature has demonstrated altered neurocircuitry encoding of 
threat and reward learning as a key mechanism linking early life abuse to worse mental health outcomes 
in adulthood. This emerging computational literature complements and extends the well-established 
link between MDD and poor reward learning and decreased reward sensitivity4–6. Indeed, in a prior 
study we demonstrated that decreased prospective reward representations in the striatum mediated 
poorer reward learning and depression symptoms among individuals with histories of early life physical 
or sexual assault7. We’ve also demonstrated decreased encoding of reward prediction errors among 
women exposed to physical or sexual assault in the striatum and anterior insula8,9, and decreased social 
reward prediction error encoding among adolescent girls who experienced physical or sexual assault. 
Similarly, recent work demonstrated altered integration of threat and reward learning (i.e., approach-
avoidance conflict) in depression10,11, potentially mediated by altered encoding of reward in the 
striatum. These findings are in line with our prior computational work investigating neurocircuitry 
mechanisms of approach-avoidance conflict demonstrating that biased prospective representations of 
reward vs threat in the salience network mediates decisions to approach reward vs avoid threat12 and 
that individuals with assault histories demonstrate altered approach-avoidance conflict learning13,14. 
Overall, the emerging literature clearly points to altered computational encoding of threat and reward 
learning as a mechanism underlying development of MDD among those with histories of early life 
assault.  
The neurocircuitry implicated in altered threat and reward learning as mechanisms of risk for MDD 
includes the salience network (dorsal anterior cingulate cortex and anterior insula) and striatum. 
Notably, this neurocircuitry overlaps with dopaminergic and serotonergic pathways targeted by atypical 
antipsychotic medications15,16. As such, altered neurocircuitry encoding of threat and reward learning 
could potentially be predictive of clinical outcomes for adjunctive therapies that target these pathways, 
such as lumateperone. There are two main routes by which these pathways could have clinically 
predictive significance. First, individual differences in neurocircuitry encoding of threat and reward 
learning could operate as markers of who would vs would not benefit from lumateperone adjunctive 

Page 34 of 58 
 
 
 
24. Will you recruit or obtain data from individuals you know to be prisoners? 
 
“Prisoner” is defined in federal regulations under 45 CFR 46.303(c) as “any individual involuntarily confined or detained in a 
penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil 
statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to 
criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or 
sentencing.” 
 
☒ No → skip to item 25  
☐ Yes  
 
24a. Provide the rationale for including this population in your research (i.e. why is a prisoner population necessary 
to answer the research questions): 
 
 
 
 
 
 
 
24b. Describe how study procedures will be designed to address each of the following: 
(a) Recruitment and subject selection procedures will be fair to all eligible prisoners; 
(b) Prison authorities or other prisoners will not be able to arbitrarily prevent or require participation of particular 
prisoners; 
(c) When applicable, control subjects will be randomly selected from the group of available prisoners meeting 
inclusion criteria (or provide a justification if selection will not be random); 
(d) When applicable, provisions will be in place to provide follow-up examinations or care of participants, taking 
into account the varying lengths of individual prisoners’ sentences, and all participants will receive information 
about how this will occur. 
 
 
 
 
 
 
 
24c. Describe how you will mitigate potential for undue coercion for prisoners to take part in the study: 
Consider whether the effect of participation on prisoners’ general living conditions, medical care, quality of food, 
amenities, and opportunity for earnings in prison might be so great as to make it difficult for prisoners to adequately 
consider the research risks. 
 
 
 
 
 
 
 
24d. Check the appropriate box(es) to attest to the following: 
☐  Researchers for this study will not encourage or facilitate the use of a prisoner’s participation in the 
research to influence parole decisions. 
therapy. Second, pre- to post-treatment changes in neurocircuitry encoding of reward and threat 
learning could operate as a mechanism of symptom reduction (e.g., lumateperone induced 
improvements in reward and threat neurocircuitry encoding mediate reductions in depression 
symptoms). These possibilities are not mutually exclusive, and both would have considerable clinical 
significance for enabling precision medicine approaches to the treatment of MDD among early life 
trauma populations. 
 
Non-English Speakers will be excluded due to inability to provide informed written consent.  
 
23. Will the study involve recruitment of the researchers’ students or personal contacts/friends/family? 
☒ No → Skip to item 24 
☐ Yes →   Explain below how the study procedures will be designed to mitigate potential for coercion or undue influence to 
participate or continue participation: 
 
 
 

Page 35 of 58 
 
☐ When applicable, each prisoner will be clearly informed in advance that participation in the research will 
have no effect on his or her parole. (Consider adding language about this in the relevant consent form(s)) 
 
 
 
25. Is your research likely to have subjects who become prisoners while participating in your study? 
For example, a longitudinal study of youth with drug problems may be likely to have subjects who will be prisoners at some 
point during the study. 
☒ No → Skip to item 26 
☐ Yes  
 
25a. If a subject becomes a prisoner while participating in your study, will you continue the study procedures 
and/or data collection while the subject is a prisoner? 
☒ No  
☐ Yes → Describe the procedures and/or data collection you plan to continue with prisoner subjects: 
 
 
 
 
 
   26. Other Protected Populations 
In this section, check the box for all other protected groups that will be intentionally targeted/discernible in your research 
(you do not need to check all groups that might be incidentally included but will not be knowingly enrolled or discernible as a 
population of study from the data collected).  
 
 
Select all that apply to this research. If 
none apply, this section can be left 
blank. 
Review the special 
considerations for selected 
group(s). 
Provide the rationale for targeting this protected 
group in your research. If this has already been 
addressed in item 22 above or elsewhere, reference 
earlier responses here, as applicable. 
Also, include any additional information you’d like 
the IRB to consider when reviewing additional 
requirements outlined in the linked policy(ies).  
☐ Minors (children) 
 
☐ Children who are wards of the 
state 
 
Note: children are considered subjects of 
the research if:  
 
1) the study involves collecting data 
about a child through an intervention or 
interaction with the child (regardless of 
identifiability of the data), OR 
 2) private, identifiable information 
about a child is collected from any 
source (e.g. interview with parent, 
medical records, educational records, 
etc.). 
Review for additional IRB 
considerations: 
UT Austin IRB Policies & 
Procedures section 12.4: 
Research Involving Children 
 
UT Austin IRB Policies & 
Procedures section 12.4.9: 
Wards 
 
NOTE: In the Consent/Assent 
Pathways section of this form, 
you will need to complete 
items 29 and 30 to address 
special consent/assent 
considerations and waiver 
options for minors. 
☐ Impaired/Incapacitated 
Adults  
Check this box if researchers will 
knowingly and prospectively enroll 
adults with conditions that impact their 
ability to make decisions for themselves 
Review for additional IRB 
considerations: 
UT Austin IRB Policies & 
Procedures section 12.5.1: 
Research Involving 
Decisionally-Impaired Adults 

Page 36 of 58 
 
 
Recruitment & Screening 
27. Recruitment Procedures and Materials 
 
and/or adults who are unconscious or 
incapacitated due to illness or condition. 
 
NOTE: In the Consent/Assent 
Pathways section of this form, 
you will need to complete 
items 29 and 31 to address 
special consent/assent 
considerations and waiver 
options for this group. 
 
 
☐ Pregnant women and fetuses 
 
☐ Neonates of unknown 
viability 
 
☐ Non-viable neonates 
Review for additional IRB 
considerations: 
UT Austin IRB Policies & 
Procedures section 12.2: 
Pregnant Women, Fetuses, 
and Neonates 
 
Select each type of recruitment method that 
will be used AND upload copies of all 
materials to UTRMS-IRB in the 
“Recruitment Materials” section.      
Describe the use of the selected method 
to recruit participants, addressing the 
specific points listed for it, when 
applicable. 
Provide the schedule and frequency of 
recruitment attempts using this 
method, when applicable. 
☐ E-mail/Letter 
 
Explain how emails/mailing addresses 
for potential subjects will be identified 
and obtained by the study team. 
Describe the initial invitation and any 
follow-up reminders, and address if 
there will be a way for recipients to 
opt-out of future emails. Templates 
should include subject line(s).  
☐ Flyer(s) 
Include the types of location(s) where 
these will be posted. 
 
☐ Social Media/Web Posts 
 
Address which sites and accounts will 
be used to post ads. Templates should 
include all text/images that will be 
included in posts. Guidance for creating 
templates for social media recruitment 
can be found on our Education & 
Guidance webpage. 
☐ Text/Direct Messaging 
 

Page 37 of 58 
 
Describe sites/accounts that will be 
used. Explain how participants’ contact 
information is obtained, when 
applicable. Templates should include 
the initial invitation and any follow-up 
reminders. 
☐ 
 
Study-specific Website 
 
This refers to websites created 
specifically for this research study. 
Templates should include 
screenshots/mock-ups of all aspects of 
the website that will be created; 
include all text/images. 
☐ In-Person or Phone 
Scripts/Presentations 
 
Explain how phone numbers for 
potential subjects will be obtained by 
the study team, when applicable. If 
researchers will be cold-calling 
subjects, provide a rationale for why 
this method is needed to accomplish 
the research. 
☐ 
 
Research Recruitment pool 
 
Specify which pool will be used (e.g. 
SONA, Prolific, Amazon MTurk, etc.) 
and describe how offered studies are 
advertised to users. Provide templates 
of all researcher-provided advertising 
language that will be posted and 
confirm it meets the pool’s standards 
for formatting, content, word limits, 
etc. 
☐ 
 
Newspaper ads/TV spots/Radio 
ads 
 
When applicable, include scripts and 
descriptions for planned ads; final 
versions can be provided in a 
modification after IRB approval.  
☐ 
 
Medical Record Review 
 
If your study includes identifying 
potential participants using PHI (e.g., a 
partial HIPAA waiver for recruitment is 
needed), note this here and be sure you 
have completed item 12 in the Study 
Elements section of this form to request 
a waiver. 

Page 38 of 58 
 
 
28. 
Screening Procedures 
Describe the procedures to screen individuals to determine whether inclusion/exclusion criteria are met. Be sure to specify 
the following specific details: 
• 
Will screening procedures occur before or after consent?  
• 
For any screening data collected prior to consent, how will this data be used? For example, will it be used only to 
confirm eligibility, screen failure analyses, or will it be used to answer the research questions as well? 
 
  Please upload all screening questionnaires/tools in the “Other Attachments” section in UTRMS.  
 
o A 2-week Screening Period during which patient eligibility will be assessed. After obtaining written 
informed consent, diagnostic interviews and physical examinations will be conducted, vital signs and ECGs 
will be assessed, and blood and urine samples will be collected for laboratory assessments. With the 
exception of stable, allowed concomitant medications, patients must discontinue prohibited psychotropic 
drugs during the Screening Period. The following rating scales will be administered. 
Clinician Rater: CAPS-5, MADRS, DIAMOND, SCID-5 Borderline Personality module, CGI-S, MGH-
ATRQ, CSSRS 
PROs, GAD-7,QIDS-SR-16, EQ 5D-5L, CTQ, GASS, PCL-5, NWS 
Once deemed eligible, the subject will also be offered to enroll in the optional EMA wellness app to be 
completed 3x daily from screening visit to the end of study visit 
 
 
Consent /Assent Pathways 
29. Consent Pathways 
Obtaining informed consent is the default expectation for enrolling subjects to your research. For all human subjects included in the 
research (either via direct participation or having their private, identifiable data included in the study), researchers must have a 
pathway either to obtain informed consent or request and meet criteria for waiving informed consent.  
 
Select all consent pathways that will be used to enroll subjects into the study.  
Examples: 
1) If you will obtain consent from one group of adult participants but are requesting a waiver for another group (such as a retrospective chart 
review group), both “Obtaining Consent from Adult Participants” and “Requesting Waiver” should be checked.  
2) If adults will provide consent for their own participation and provide consent for their child’s participation, both “Obtaining Consent from Adult 
Participants” and “Obtaining Parent/Guardian Consent for Minor Participants” should be checked, etc.  
 
☒ Obtaining Informed Consent (verbal or written) from: 
 ☒ Adult Participants for their own participation 
 ☐ Parent(s)/Guardian(s) for Minor (child) Participants 
 ☐ Legally Authorized Representative (LAR) for impaired/incapacitated adult participants 
☐ Requesting Waiver or Alteration of Required Elements of Informed Consent  
☐ Obtaining Short Form Consent with a witness (rare, limited applicability, see Policies & Procedures section 6.4.2) 
 
☒ Other recruitment 
material/method 
Department referral registry 
2020040046 (IRB number) 
 
29a. Obtaining Consent Description → if not obtaining consent for any group, skip to 29b 

Page 39 of 58 
 
 
29b. Waiver or Alteration of Informed Consent Requested 
Select the type(s) of consent waivers being requested or select “None requested”.  
Note this section is for requesting a full consent waiver or waiving part(s) of the required information typically provided in consent 
forms. Signature-only waivers are addressed in item 29d below. 
  
Select all that apply. 
☐ Waiver of Informed Consent for Adult Participants  
☐ Waiver of Parental/LAR Consent for Child or Impaired/Incapacitated Adult  
☐ Alteration of Required Elements of Informed Consent and/or Parental or LAR consent (e.g. Deception research where 
the nature of the research cannot be fully disclosed)  
☐ None requested → Skip to item 29d 
 
In the box below, specify how each “obtaining consent” method checked in the table above will be used and with which 
participant group(s).  
For each method checked, include who will obtain consent, where consent will be obtained, and when the consent process will 
occur in such a manner that participants will have sufficient time for adequate consideration.   
 
NOTE: Upload copies of all consent/permission forms/scripts to UTRMS-IRB in the “Consent Forms” section. This is required for 
UTRMS-IRB to appropriately stamp consent forms for approval.  
 
 
During the screening period, the participant will be given a written and verbal description of the study and 
informed consent. The PI or designated staff will discuss the informed consent form with the subject 
volunteer. The consent process will take place in a quiet and private room. Subjects may take as much 
time as needed to decide about their participation and may take the document home if desired. The person 
obtaining consent will thoroughly explain each element of the document and outline the risks and benefits, 
alternate treatment(s), and follow-up requirements of the study. Participation privacy will be maintained 
and questions regarding participation will be answered. No coercion or undue influence will be used in the 
consent process. No research-related procedures will be performed prior to obtaining informed consent. 
All signatures and dates will be obtained. A copy of the signed consent will be given to the participant. 
The informed consent process will be documented in each subject’s research record.  
29c. Qualification for Waiver or Alteration  
 
To approve a waiver or alteration of informed consent all of the following criteria below must be met. 
 
 
Criterion 1: The research involves no more than minimal risk to the subjects.  
Provide protocol specific information as to how this criterion is met. Consider how the risk(s) of the research activity(ies) for 
which consent is being waived compare to the risks the average person might reasonably anticipate experiencing in everyday 
life: 
 
 
 
 
 
 
 
 
Criterion 2: The waiver or alteration will not adversely affect the rights and welfare of the subjects.  
Provide protocol specific information as to how this criterion is met. Consider whether this waiver may violate the rights of 
subjects or adversely affect their welfare in any way.  For example, if the research proposes to use data that was originally 
collected under an explicit agreement that it would not be used for research purposes, this waiver might violate participants’ 
rights. 
 
 
 
 

Page 40 of 58 
 
 
29d. Consent Signature Type 
Select the method(s) for obtaining participant signatures for informed consent. Select all that apply to your research. 
 
☒ Written Signature (on paper or with finger/mouse/stylus on touchpad or computer)   
☐ Electronically-generated Signature using standard validation service (such as DocuSign or REDCap)  
☐ Electronically-generated Signature using externally-hosted validation service that is Part 11 compliant → see note: 
Part 11 compliance is required for studies falling within FDA regulations (i.e. investigational drugs/devices). At this time, the UT 
system accounts for REDCap and DocuSign are not compliant with the requirements of Part 11. FDA-regulated studies 
conducted at UT that collect electronically-generated consent signatures may utilize an FDA-compliant account managed 
by an external sponsor or a collaborating institution (as applicable); otherwise, researchers must utilize written consent. For 
additional guidance on Part 11 compliance, contact regsupport@austin.utexas.edu. 
☐ Obtaining consent without valid signature – waiver of signature requirement requested → Complete Section 29e 
☐ N/A - Not Obtaining Consent  
 
 
 
 
 
 
Criterion 3: The research could not practicably be carried out without the waiver or alteration (i.e. the research 
would not be achievable or viable if obtaining consent is required). 
Provide protocol specific information as to how this criterion is met. Acceptable justifications should be based on the study's 
scientific design rather than issues of time or inconvenience. For example, is there evidence to suggest significant portions of 
the sample would be unreachable and present significant sampling bias? Is the nature of the research such that a total 
population sample is necessary to answer the research questions? 
 
 
 
 
 
 
 
 
 
 
Criterion 4: The research either does not involve using identifiable private information or identifiable 
biospecimens, or if identifiable data/specimens are used, the research could not feasibly be carried out without 
using such information or biospecimens in an identifiable format. 
i.e. Why would it be impossible to conduct the study using only anonymous information/specimens? Provide protocol specific 
information as to how this criterion is met:  
 
 
 
 
 
 
 
29e. Waiver of Documentation (signature) of Informed Consent → if not requesting, skip to item 30 
 
Only complete this section if you are requesting to waive the requirement to collect a written or validated electronic signature 
of informed consent from participants (an informed consent form/script is still required). To approve a waiver of 
documentation of consent, all criteria for one of the following options must be adequately justified by the researcher.  
 
Please choose one waiver option and address the listed criteria as prompted. Waiver Option 1 is most common.  
 
 
i. Waiver Option 1 – Minimal Risk Research 
Each criterion listed below must be met to qualify for Waiver 1.   
Criterion 1: The study is minimal risk. 
Provide protocol specific information as to how this criterion is met.  Consider how the risk(s) of the research 
activity(ies) for which consent is being waived compare to the risks the average person might reasonably anticipate 
experiencing in everyday life: 

Page 41 of 58 
 
 
Criterion 2: Written consent would not be required outside the research context. 
Provide protocol specific information as to how this criterion is met. For example, if laws or other regulations requiring 
signed consent would normally be applicable to the type of research activity for which signed consent is being waived 
outside of a research context, this criterion is not met (e.g. consent for clinical care, consent for release of educational 
records, signing a housing application or similar contract, etc.).    
 
Criterion 3: There will be an appropriate alternative mechanism for documenting that informed consent 
was obtained. 
Briefly explain how the researcher will document that consent was obtained from participants: 
 
 
 
ii. Waiver Option 2 – High Risk for Confidentiality Breach (rare) 
Each criterion listed below must be met to qualify for Waiver 2. 
NOTE: This is the only applicable waiver of documentation option for greater than minimal risk research. If your study is 
greater than minimal risk and does not meet Option 2 criteria, you will need to obtain signed consent. 
 
Criterion 1: The only record linking the subject and the research would be the consent document. 
Provide protocol specific information as to how this criterion is met. 
 
Criterion 2: The principal risk would be potential harm resulting from a breach of confidentiality. 
Provide protocol specific information as to how this criterion is met. 
 
 
Criterion 3: Each subject will be asked whether the subject wants documentation linking the subject with 
the research, and the subject’s wishes will govern. 
Provide protocol specific information as to how this criterion is met. Note that under this waiver, participants must be 
given the option to sign or not, so the consent form(s) will still need signature lines.  
 
 

Page 42 of 58 
 
 
 
30. Assent Pathways for Research Involving Minors (children)  
This section is required for all studies involving minors as subjects (see the Other Protected Populations section for 
guidance). If this study does not involve minors, skip to item 31. 
 
Select all that apply: 
☐ Obtaining Assent from Minor (child) Participants 
☒ Not Obtaining Assent → If only this box is checked, skip to item 30b 
 
Criterion 4: There will be an appropriate alternative mechanism for documenting that informed consent 
was obtained. 
Briefly explain how the researcher will document that consent was obtained from participants who do not sign. 
 
iii. Waiver Option 3 – Cultural Norms (rare) 
Each criterion listed below must be met to qualify for Waiver 3. 
Criterion 1: The subjects or legally authorized representatives are members of a distinct cultural group or 
community in which signing forms is not the norm. 
Describe the cultural group or community and explain how this criterion applies: 
 
 
 
 
 
Criterion 2: The research presents no more than minimal risk of harm to subjects. 
Provide protocol specific information as to how this criterion is met.  Consider how the risk(s) of the research activity(ies) 
for which consent is being waived compare to the risks the average person might reasonably anticipate experiencing in 
everyday life: 
 
Criterion 3: There is an appropriate alternative mechanism for documenting that informed consent was 
obtained. 
Provide protocol specific information as to how this criterion is met and describe the mechanism for documenting that 
informed consent was obtained: 
 
30a. Assent Process Description 
 
Provide a detailed description of assent procedures in the box below. Include: who will obtain assent, where assent will be 
obtained, how assent is obtained, how assent is documented, and when the assent process will occur.  
 
NOTE: Upload copies of all consent/assent/permission forms/scripts to UTRMS-IRB in the “Consent Forms” section. This is 
required for UTRMS-IRB to appropriately stamp consent forms for approval.  
 
 
 
 

Page 43 of 58 
 
 
30b. Waiver of Assent for Minors Requested 
Note: Assent is generally not required for children age 0-6, so a waiver does not need to be requested for this age group.  
 
☐ Waiver of Assent for Children age 7+  
☒ None requested → skip to item 30f 
 
30c. Qualification for Waiver of Assent from Minors (children) age 7+ (select all that apply) 
 
☐ Some or all children age 7+ included in this research will not be capable of providing assent based on their 
developmental status or impact of illness/condition. → If checked, explain below:  
 
 
 
 
 
 
 
☐ Requesting a waiver of assent from some or all children age 7+ who are otherwise capable of providing 
assent → If checked, address all of the following. All of the following criteria must be met to request a waiver: 
 
 
 
Criterion 1: The research involves no more than minimal risk to the subjects.  
Provide protocol specific information as to how this criterion is met.  Consider how the risk(s) of the research activity 
for which consent is being waived compare to the risks the average child might reasonably anticipate experiencing 
in everyday life: 
 
 
 
 
 
 
 
 
 
 
 
 
Criterion 2: The waiver or alteration will not adversely affect the rights and welfare of the subjects.  
Provide protocol specific information as to how this criterion is met. Consider whether this waiver may violate the 
rights of subjects or adversely affect their welfare in any way.  
 
 
 
 
 
 
 
 
 
 
 
Criterion 3: The research could not practicably be carried out without the waiver or alteration (i.e. the 
research would not be achievable or viable if obtaining assent is required). 
Provide protocol specific information as to how this criterion is met. Acceptable justifications should be based on the 
study's scientific design rather than issues of time or inconvenience.  
 
 
 
 
 
 
 
 
 
 
 
Criterion 4: The research either does not involve using identifiable private information or identifiable 
biospecimens, or if identifiable data/specimens are used, the research could not feasibly be carried out 
without using such information or biospecimens in an identifiable format. 
i.e. Why would it be impossible to conduct the study using only anonymous information/specimens from minors? 
Provide protocol specific information as to how this criterion is met: 
 
 
 
 

Page 44 of 58 
 
30d. Minor Assent Signature Type 
Select the method(s) for obtaining participant signatures for assent. Select all that apply to your research. 
Note that validation services such as DocuSign cannot be used to validate signatures from minors. 
 
☐ Written Signature (on paper or with finger/mouse/stylus on touchpad or computer) 
☐ Obtaining assent without signature for children age 12 and younger 
☐ Obtaining assent without signature for children age 13-17 → Complete 30e below  
☐ N/A - Not Obtaining Assent  
 
 
30e. Request to waive Assent Signature Requirement for Minors (children) age 13-17 → if not requesting, 
skip to item 30f.  
 
Only complete this section if you are requesting to waive the policy requirement to collect a written signature of assent 
from participants age 13-17. The IRB will assess the rationale provided by the researcher for appropriateness based on the 
specific study procedures and population.  
 
 
i. Provide a protocol specific justification for why written assent signature will not be obtained: 
 
 
 
ii. Describe the mechanism for documenting that assent was obtained. 
Briefly explain how the researcher will document that assent was obtained from participants  
30f. Age of Majority Re-Consent Process 
The age of majority is the age at which a person is legally considered an adult and can provide informed consent for their 
own participation in research. In most states, including Texas, the age of majority is 18, but this can vary depending on 
where the research is conducted.   
 
If the research involves minors as subjects, either Option 1 or Option 2 below must be checked: 
 
☐ Option 1: All study activities with minors will be complete AND all data collected from minors will be 
anonymized before any participants will reach age of majority. 
 
 
☐ Option 2: The study enrolls minors who may reach age of majority while study activities and/or research use 
of their identifiable data is ongoing.  
If true, specify the method of obtaining adult informed consent from these participants upon reaching age of majority. At 
least one of the following must be checked: 
 
☐ Participants will be re-consented using an adult consent form/script 
 
Describe the re-consent procedures below. Be sure to upload an adult consent document that will be used for this 
group. If signature will not be collected (e.g. if re-consent is conducted via phone or other remote method), please 
complete item 29e to request a waiver of documentation (signature). 
 
NOTE: Upload copies of all consent/assent/permission forms/scripts to UTRMS-IRB in the “Consent Forms” 
section.  
 
 
 

Page 45 of 58 
 
 
31. Assent Pathways for Research Involving Impaired/Incapacitated Adults 
This section is required for all studies where impaired/incapacitated adults are knowingly and prospectively enrolled (see 
the Other Protected Populations section for guidance). If this study does not involve this population, skip to item 32. 
 
 
     31b. Impaired/Incapacitated Adult Assent Pathway Select all that apply 
      ☐ Obtaining Assent from Adult Participant  
      ☒ Not Obtaining Assent → if only this box is checked, skip to item 32 
 
     31d. Impaired/Incapacitated Adult Assent Signature Type Select all that apply 
 
      ☐ Written Signature obtained when possible (on paper or with finger/mouse/stylus on touchpad or computer) 
      ☐ Electronically-generated Signature obtained when possible, using validation service (such as DocuSign) 
      ☐ Obtaining assent without signature 
Additional Consent Considerations and Disclosures 
 
 
 
 
☐ A waiver of adult re-consent is requested in the Waiver or Alteration of Informed Consent section of 
this form.  
31a. Capacity for Consent/Decision-Making Capacity 
 
Describe the process you will use (if any) to determine whether a cognitively impaired individual is capable of consent 
decision making with respect to this research protocol and setting. 
Consent pathways for adults who are capable of providing full informed consent (instead of assent) should be covered in 
item 29 above. 
 
 
 
 
31c. Assent Process Description 
 
Describe whether assent will be required for all or some of the subjects. If some, indicate which subjects will be required to 
assent and which will not (and why not).  
Provide a detailed description of assent procedures in the box below. Include: who will obtain assent, where will assent be 
obtained, how is assent obtained and documented, and when the assent process will occur in such a manner that 
participants will have sufficient time for adequate consideration.   
 
NOTE: Upload copies of all consent/assent/permission forms/scripts to UTRMS-IRB in the “Consent Forms” section. This is 
required for UTRMS-IRB to appropriately stamp forms for approval.  
 
 
 
 
32. Will the study population likely include participants whose limited English-speaking status requires 
translation of the consent/assent documents and other relevant study materials? 
☒ No → skip to item 33 
☐ Yes 
 
32a. Translation Process 
Complete the below information describing the translation process. One of the following must be checked. 
 

Page 46 of 58 
 
 
Compensation & Costs 
 
☐ The consent documents and other relevant study materials will be translated by a certified translator. 
☐ A non-certified translator will translate the consent documents and other relevant study materials and 
another individual will confirm the translation is accurate and appropriate. → If selected, describe the translator’s 
qualifications in the text below: 
 
 
 
 
33. Required Consent Disclosures  
Identify each element below that may require additional information to be disclosed in the consent form. 
 
 
☒ It is reasonable that researchers could discover or suspect child or elder abuse. 
Add appropriate disclosure in consent form(s). 
☒ It is reasonable that researchers could learn of an incident that could require reporting under Title IX. 
Add appropriate disclosure in consent form(s). See Title IX and Research Guidance for more information on this requirement.  
☒ It is reasonable that researchers could discover incidental findings or other information of medical interest 
about a participant's previously unknown condition. → answer the following: 
 
            33a. Articulate methods for addressing and reporting incidental findings, if applicable. 
              If results will not be shared, provide a justification for why this will not occur. Ensure appropriate information is in 
             consent form(s), as applicable. If the study involves genetic testing that could result in relevant findings, this should be 
addressed in item 11d and that response can be referenced below.  
 
 
 
 
During the MRI there is a small chance that incidental findings may occur. If this happens, 
researchers will send the images to the Biomedical Imaging Center’s Safety Panel where they will 
be reviewed by the Medical Director or designated qualified radiologist.  
 
 
 
33b. If research will be conducted at the UT Biomedical Imaging Center (BIC), check the box below to 
attest that researchers will comply with BIC requirements for reporting incidental findings, as outlined in 
the BIC Wiki. Ensure appropriate language is included in all relevant consent forms. As a reminder, research 
conducted at the BIC is required to comply with all BIC policies/requirements. This can be left blank if not applicable 
(i.e. no research activities at the BIC).  
☒ Confirm 
34. 
 
 
 
 
Will subjects receive any compensation for their participation in the research?  
See P&P section 4.8 for guidance on compensation.  
☐ No → skip to item 35 
☒ Yes 
 
34a. Specify the type/total amount of compensation that will be provided to each participant: 
 
You will receive a stipend of $50 for each study visit you complete. In addition, you will receive an extra 
$50 for Visit 2 and Visit 8 if you complete the imaging procedures scheduled during those visits. This 
means you may receive additional compensation for participating in specific procedures that require 
more time or effort. 

Page 47 of 58 
 
 
Benefits 
36. 
Benefits to Society 
Describe the scientific and societal benefit(s) below. 
 
 
There is a great unmet need for novel treatments for MDD. There are few approved medications, for 
Major Depressive Disorder, and although effective, similar to evidence-based therapies, they produce a 
significant improvement in symptom severity scores, but bring few patients into remission. The 
purpose of the study is to determine if Lumateperone (oral) reduces MDD symptom severity in adult 
subjects diagnosed with MDD and have a history early life trauma.  
All stipends will be provided through Tango Cards, which can be redeemed for a variety of gift cards or 
charitable donations. 
 
34b. Indicate the type(s) of compensation offered: Select all that apply 
☐ Cash                   ☐ ClinCard 
☐ Check                 ☒ Tango Card  
☐ Gift Card            ☐ Course Credit 
☐ Other, describe in the text box below: 
 
 
 
 
 
 
 
 
34c. Will monetary payments be pro-rated so that participants who are unable to complete the research may 
still receive some part of payment? (e.g. hourly rate, split across multiple study sessions, payment per activity 
completed, etc.) 
It is recommended that payment be prorated for the time of participation in the study rather than delayed until study 
completion, as making payment contingent on completing multiple sessions could unduly influence a subject’s decision to 
exercise their right to withdraw at any time. It is acceptable, with an appropriate justification, to offer an additional incentive 
or completion bonus to subjects that complete all study activities, provided the incentive is not so large as to unduly influence 
subjects to stay in a study when they otherwise would have withdrawn. 
 
☐ No → skip to item 35 
☒ Yes → describe the proration schedule in the text box below: 
 
 
For each task/visit a participant completes, they will receive $50. In addition, you will receive an extra $50 
for Visit 2 and Visit 8 if you complete the imaging procedures scheduled during those visits. . 
35. Costs 
One of the following must be checked:  
☒ Participants will have no costs associated with this study → skip to item 36 
☐ Participants will have the following costs associated with this study:  
☐ Standard of care procedures contributing to study data 
 
☐ Research procedures/services not associated with standard of care 
☐ Administration of drugs/devices  
☐ Study drugs or devices 
☐ Transportation and parking 
☐ Other, describe below: 
 
 
 
 
 
 

Page 48 of 58 
 
 
37. 
Potential Direct Benefits to Participants 
Click on the applicable check box. One of the following must be checked.  
 
☐ There is no anticipated direct benefit to participants. 
☒ There are anticipated benefits to participants. → Describe potential direct benefits to participants below. Note 
that compensation (addressed in previous section) is not considered a “benefit” of research participation: 
 
 
 
Patients might notice a reduction in MDD symptoms. 
 
 
38. 
Alternatives to Participation in this Study 
Provide a description of any alternative procedures or treatments that might be advantageous to the subjects. For example, 
earning extra class credit in some time-equivalent way other than research participation; obtaining supportive care or 
standard clinical treatment from a health care provider instead of participating in research with an experimental drug or 
intervention, etc.   
 
 
 
 
 
 
Risks & Discomforts 
39. 
Describe all reasonably foreseeable risks and discomforts associated with each activity in this 
research:  
Transparency about all risks/discomforts, even those that are minimal, increases participant trust in the research 
enterprise and helps to prevent unanticipated problems or complaints. It is rarely acceptable to state there are “no risks.” 
However, you are encouraged to provide your evaluation of the probability and magnitude of potential risks listed.  
 
Categories of possible risks to consider may include (but are not limited to) the following: 
• 
Physical (e.g. bodily harms or discomforts, side effects, etc.); 
• 
Psychological/emotional (e.g. boredom or mental fatigue, discomfort answering questions or providing personal 
information, learning unpleasant information about oneself or others, etc.); 
• 
Social or legal (e.g. impacts on relationships or reputation, legal or criminal justice actions for self or others, etc.); 
• 
Financial or economic (e.g. impacts on income, employability, or insurability, loss of services, etc.); 
• 
Research Design-specific risks (e.g. unforeseeable risks of experimental procedures, disappointment with 
randomization outcomes, washout risks, placebo effects, withholding or delaying care/services, deception, etc.). 
 
General loss of privacy/confidentiality is an assumed, foreseeable risk that applies to all studies as data breaches or other 
errors of this nature are not uncommon. This general risk does not need to be reiterated below, but if there are more 
specific privacy/confidentiality risks associated with the research, these can be described. All foreseeable risks/discomforts 
must also be outlined in the consent form(s).  
 
 
 
Privacy: There is a low risk of loss of confidentiality of your personal information. While every effort 
will be made to protect the confidentiality of your information, absolute confidentiality cannot be 
guaranteed. However, steps have been taken to help make sure this will not happen. You will read 
more about the protection of your personal information in Part 3 of this information sheet. 
ECG: Some areas where the electrodes (sticky patches) will be placed may need to be shaved. The test 
is painless, but the electrodes may irritate your skin. 

Page 49 of 58 
 
Blood tests: Drawing blood may cause discomfort, bruising, and very rarely, infection at the puncture 
site, or damage to a vessel or a nerve. You may also experience dizziness, nausea, or fainting during 
the blood-taking procedure. Please tell the study doctor or study team if you do not feel well after 
having your blood drawn. 
Questionnaires and interviews: Some of the questions that you may be asked during the study may 
be sensitive, which can be distressing for some people. If you feel uncomfortable as a result of the 
study questionnaires or an interview, please tell the study doctor or a member of the study team. 
Fasting: Fasting could cause dizziness, headache, stomach discomfort, or fainting. 
MRI Scan: No serious ill effects have been reported to date from facilities in the United States 
operating with a magnetic field strength of 3 Tesla (the magnetic field strength used in this study); 
these types of magnets are widely used for clinical practice.  Since the study involves entering a 
confined space, you may not be able to participate if you have a history of claustrophobia or if you 
experience anxiousness when entering the magnet tube. 
The risks due to exposure to the magnet itself are primarily related to the slight possibility of a 
sensation of dizziness or nausea as you move in and out of the magnet or move your head in the 
magnet.  The magnet is thought to be able to exert a force on the fluid within the semicircular canals 
near the ears thus possibly giving a sensation of dizziness.  The sensations go away if your head is not 
in motion or if you are not moving in/out of the magnetic field.  Less than 10% of subjects experience 
this dizziness, which generally lasts 1-2 minutes or less.  You will be exposed to noise from the 
machine for which earplugs and/or earphones are provided.  There are no other known risks to being in 
the magnetic field. 
Magnetic items move in a high magnetic field and by doing so, can be dangerous. The Biomedical 
Imaging Centers (BIC) at the University of Texas at Austin is careful to maintain an environment safe 
from these objects. We require you to do the same, being careful to ensure that you carry no metallic 
items into the MRI room.  You will be asked to change into MRI-approved clothing for the MRI scans. 
We want you to read and answer very carefully the questions on the MR Safety Questionnaire related 
to your personal safety.  Take a moment now to be sure that you have read the MR Safety 
Questionnaire and be sure to tell us any information about you that you think might be important.  
Electrical shocks: During the MRI scan you will complete a task during which you will receive mild 
electrical shocks. Prior to entering the scanner, you will select a level of shock that is annoying and 
mildly uncomfortable but not painful. If the shocks become too uncomfortable or distressing for you, 
you can stop the MRI scan at any time by alerting the research staff. 
Harm to the unborn child: Currently, we are not fully aware of the effects of the study drug on 
unborn babies, or people who are pregnant or breastfeeding. If you can become pregnant, use of the 
study drug may lead to new, previously unknown, side effects that we currently do not know about, 
and this may involve risks to your unborn baby. Because of this, subjects who can have children will 
have pregnancy tests (blood and/or urine) during the study. Sexually active subjects who can become 
pregnant must be using an effective form of birth control from the screening visit until the end of the 
follow-up. The study doctor will discuss effective birth control methods with you. 
If you become (or your partner becomes) pregnant during the study, you should immediately tell the 
study doctor. If you become pregnant, you will have to stop taking the study drug. Your pregnancy and 
health will be followed carefully by the study team. Female partners of male subjects who become 
pregnant will be asked to provide consent for the study team to follow their pregnancy and health until 
the end of the pregnancy. 
 

Page 50 of 58 
 
 
 
 
40. 
Describe how each risk listed above is mitigated/minimized. 
General privacy and confidentiality protections do not need to be outlined here as these are covered in their own section 
below. Mitigation strategies for all other risks/discomforts described above should be outlined. Risk mitigation should also 
be outlined in the consent form(s), when applicable.  
 
 
All study procedures occur after the Informed consent is obtained from participants which specifically 
outlines the risks associated with participation in the study and from blood draws and imaging 
procedures. Study participants will be educated about the procedures involved, including potential risks 
and what to expect before, during, and after these procedures are completed. Participants will be 
encouraged to report any unusual symptoms or reactions promptly. Only those personnel trained and 
experienced in performing these tasks safely and accurately will conduct all study related procedures 
such as blood draws and imaging. Study personnel will ensure all equipment for study procedures is 
properly calibrated, maintained, and validated for accuracy. Prompt reporting and documenting of any 
adverse events or reactions that occur during study procedures will be implemented to prevent 
recurrence.  
  
 
41. 
Early Withdrawal 
Are there any planned or anticipated conditions under which a participant will be withdrawn from the study without their 
consent, and/or any safety issues for participants who choose to withdraw early? Be sure your response aligns with any 
information about withdrawal included in the consent form(s): 
 
☐ No → skip to item 42 
☒ Yes → answer the following: 
 
 
 
41a. List the criteria for withdrawing individual participants from the study:  
Examples may include, but are not limited to, safety or toxicity concerns, emotional distress, inability to comply 
with the protocol, or requirements from study sponsor, etc. 
 
 
 
Safety or toxicity concerns, emotional distress, inability to comply with the protocol, or requirements 
from study sponsor. 
 
 
 
 
 
41b. If applicable, describe any necessary procedures for ensuring the safety of a participant who 
withdraws/has been withdrawn early. 
 
 
 
 
 
 
 
42. 
Data Safety Monitoring  
Studies involving investigational drugs or devices are generally required to at least have a data safety management plan 
(DSMP), regardless of risk level. Studies that involve greater than minimal risk are strongly recommended to have a 
DSMP, and the IRB may require this in certain circumstances (e.g. if there is a known risk with expected frequency, etc.). 
Some studies, particularly those that are greater than minimal risk and involve sponsors or federal funding, may have a 
data safety monitoring board or committee that oversees ongoing safety reviews.  
 
Otherwise, most minimal risk studies do not require a data safety plan or board, though sponsors or the IRB may require 
this under certain circumstances. 
 

Page 51 of 58 
 
For additional information and reporting requirements regarding data safety monitoring boards and data safety 
monitoring plans, please see Section 21 of our Policies and Procedures. 
 
After reviewing the information above, one of the following must be checked: 
 
☐ This study does not involve a Data Safety Monitoring Plan (DSMP) or a Data Safety Monitoring Board 
(DMSB). → skip to item 44 
☐ This study has an internal plan to monitor data for safety (Data Safety Monitoring Plan (DSMP)).  
☒ This study has a Data Safety Monitoring Board or Committee (DSMB/C). 
 
43. 
Data Safety Monitoring (Details) select all that apply 
☐ This study has a DSMP document or DSMB charter describing safety monitoring details (including 
the list of board members for DSMBs) uploaded to UTRMS → if all details below are covered in the 
uploaded document, skip to item 44 
☒ Details of the DSMP/DSMB processes are provided below: 
 
 
 
43a. Describe the safety information that will be collected and reviewed for safety monitoring.  
This description should include the following details: 
• 
the type(s) of information that will be collected to monitor individual participant safety  
• 
any additional cumulative data that will be collected to monitor overall study safety (if different from 
what is obtained for participant monitoring) 
• 
the schedule and frequency of safety data collection  
 
 
 
1. Adverse Events 
Adverse events will be collected after the ICF has been signed through the end of 
the study.  Medical conditions or AEs that occur after the ICF has been signed and 
prior to completion of screening will be captured on the Medical History CRF.  
2. Medical History 
At screening the subject’s clinically significant pre-existing medical conditions will 
be documented.  The history should include demographic information and relevant 
medical history with an emphasis on the subject’s history of present illness and 
treatment history. Surgical history will be recorded.  
3. Physical Exam  
Body weight and height will be measured at screening. Any condition present at 
the post-treatment physical examination that was not present at or worsened since 
the baseline examination is to be documented as an AE. Whenever possible, the 
same individual is to perform all physical examinations. Physical examinations will 
include assessment of body systems (e.g., HEENT, heart, lungs, abdomen, and 
extremities) as well as cognitive and neurological examination and mental status 
examination. 
4. Vital Signs  
Vital signs include oral temperature (°F), respiratory rate, heart rate, and blood 
pressure. A full set of vital signs will be obtained at all specified time points (±30 
minutes), unless the subject is asleep between the hours of 23.00h and 06.00h each 
day. 
5. ECG 
A baseline 12-lead ECG will be performed during screening. The following ECG 
parameters will be recorded: heart rate, PR, QRS, QT, and QTc. All ECG results 
will be interpreted by the Investigator as Normal, Abnormal; not clinically 

Page 52 of 58 
 
significant (NCS), or Abnormal; clinically significant (CS). If Abnormal, details 
will be provided. 
6. Clinical Laboratory Tests 
Blood samples will be collected for hematology, serum chemistry, coagulation, 
specific hormone parameters, and exploratory biochemistry; and pregnancy testing. 
Urine samples for urinalysis and selected drugs of abuse will also be collected. All 
samples will be analyzed at the local laboratory.  
 
All clinical laboratory test results outside the reference range will be interpreted by 
the Investigator as Abnormal; not clinically significant (NCS) or Abnormal; 
clinically significant (CS). Screening results considered Abnormal; CS will be 
recorded as medical history.  
 
Clinical laboratory results that are Abnormal; CS during the study and indicate a 
worsening from baseline will be considered AEs.  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
Suicidality will be monitored during the study using the C-SSRS (Posner et al., 2011). This 
scale consists of a screening/pre-dose evaluation that assesses the lifetime and recent 
experience of the subject with suicidal ideation and behavior, and a post-baseline evaluation 
that focuses on suicidality since the last study visit. The C-SSRS includes “yes” or “no” 
responses for assessment of suicidal ideation and behavior as well as numeric ratings for 
severity of ideation, if present (from1 to 5, with 5 being the most severe). The 
“Baseline/Screening” C-SSRS form will be completed at screening prior to dosing.  
 
 
 
 
 
43b. Describe the data safety monitoring review process.  
This description should include the following details: 
• 
Who will be responsible for reviewing safety data and identifying safety concerns? 
• 
How frequently will safety data be reviewed by the responsible person(s)/board? 
 
 
 
The PI and DSMB will be ultimately responsible for monitoring the safety and efficacy of the 
trial, executing the DSM plan, and complying with reporting requirements. Any adverse 
events (AE) that occur will be monitored in an ongoing way, as well as being formally 
reviewed by the investigators and at each annual review meeting. Any data accrued will be 
summarized and reviewed by the study investigators at each annual review meeting and after 
50% of participants have been enrolled. Interim analyses will not be performed unless 
clinically indicated. All SAEs, such as death, hospitalization, will be reported to the IRB, 
FDA, and the sponsor under expedited reporting in accordance with policy. The procedures for 
this reporting include written documentation using the clinical notes related to the adverse 
event and specific forms detailing the event with a sign-off by all appropriate supervisory 
personnel. We will report major protocol amendments or changes in the informed consent to 
the sponsor, as well as any temporary or permanent suspension of patient accrual. 
 
The board will include Zach Stowe, University of Wisconsin Madison, Thomas Adams, Yale 
University, and Ben Kelmendi, Yale University 
 
 
 
 
 
 
 
43c. Describe any pre-specified safety threshold or criteria that would trigger immediate 
suspension of the study, if applicable. 

Page 53 of 58 
 
 
 
 
It would depend on the evaluation of serious adverse events. 
 
 
 
Privacy & Confidentiality 
 
44. Participant Privacy 
Privacy refers to an individual’s right to control how others view, record, or obtain information about them. Privacy 
protections apply to people, while confidentiality protections (addressed in the next item), apply to data. 
 
In this section, describe how the study team will protect participants’ privacy throughout all phases of the research, 
including during identification, recruitment, screening, the consent process, the conduct of the study, and dissemination of 
data. For example, consider the locations where you will approach and question participants, the locations where data will 
be viewed/analyzed, how data collection procedures will limit the amount of sensitive or invasive data collected to only 
what is necessary to answer the research questions, how participants will be described in publications/presentations, etc. 
  
 
The study team is committed to safeguarding participant privacy throughout all phases of the research, including 
identification, recruitment, screening, consent, study conduct, and dissemination of findings. The following 
measures will be implemented: 
• 
Potential participants will be identified through secure, IRB-approved databases or referrals from 
clinical providers, ensuring no unauthorized access to personal health information (PHI). 
• 
Recruitment will occur in private settings (e.g., clinic rooms, secure telehealth platforms) to prevent 
inadvertent disclosure of participation. 
• 
Screening will be conducted in private locations or via secure, encrypted platforms. 
• 
Only data necessary to determine eligibility will be collected, minimizing exposure to sensitive 
information. 
• 
The consent process will occur in a confidential setting, with ample time for participants to ask 
questions. Consent forms will clearly outline data privacy protections and participants’ rights. 
• 
Participants will be described in aggregate and no identifying information will be shared in any 
dissemination materials. 
• 
Data analysis will be conducted on de-identified datasets whenever possible. 
 
 
 
45. Data Confidentiality and Security Plan 
Confidentiality refers to the way private information about a participant or defined community is maintained and shared. 
It describes how the study’s research materials (data, specimens, records, etc.) are protected from unauthorized access.  
 
In this section, describe whether any participant identifiers (e.g. names, contact info, etc.) will be collected during the 
conduct of the research and if identifiers will be linked to research data for any period of time. Include the following, as 
applicable: 
• 
If identifiers will be used for contact or compensation purposes only, and will never be linked to specific 
responses, describe the methods used to accomplish this. 

Page 54 of 58 
 
 
 
• 
If identifiers will be coded/pseudonymized to protect confidentiality, describe whether or not a code key will be 
created linking study IDs/pseudonyms to identifiers, who will have access to the key, and how it will be stored 
separately from the research data. 
 
• Study procedures will be designed to collect only the minimum necessary data to answer the 
research questions, avoiding unnecessary invasiveness. 
• All data will be collected using secure, encrypted systems 
• Physical documents will be stored in locked cabinets in restricted-access areas; electronic data 
will be stored on password-protected, access-controlled servers. 
• Only authorized study personnel will have access to identifiable data, and all team members 
will complete required subjects protection training. 
• Data analysis will be conducted on de-identified datasets whenever possible. 
Identifiers will be indirectly linked to the study data via a secure linking log that associates participant 
names with subject ID numbers. It will be stored exclusively on UT Austin’s encrypted and access-
controlled servers, and access will be restricted to IRB-approved study personnel. 
 
Identifiable information will not be included in the primary study dataset used for analysis, and all 
identifiers will be destroyed following study closeout in accordance with UT data retention policies 
and IRB protocol. All study data used for analysis will be de-identified, and the linking log will be 
stored separately from the dataset to maintain confidentiality. 
 
46. Does the study have (or do you plan to apply for) a Certificate of Confidentiality from the National 
Institute of Health (NIH)? 
☐ No  
☐ Yes - NIH has issued a Certificate of Confidentiality for this study.  
       Ensure CoC language is included in the consent form(s).  
☒ Yes - a Certificate of Confidentiality has not been obtained, but there are plans to apply for one. 
Apply for a CoC for non-NIH funded research here: NIH Certificate of Confidentiality System. Once CoC is granted by 
NIH, you must submit a modification to add CoC language to the consent form and ensure a copy of the CoC approval 
(only for non-NIH funded research) is uploaded to UTRMS-IRB.  
 
 
47. Electronic Materials - Storage and Access 
In this section, select all methods that will be used to protect the confidentiality of research data.  
At least one of the following must be checked, select all that apply.  
 
☒  Electronic data and records will be stored on a password-protected cloud service that is currently listed as 
approved on the UT Information Security Office (ISO) platform matrix.  Access to data will be limited only to 
individuals who need access for purposes related directly to this research study. (Strongly recommended) 
The matrix of current UT Austin ISO approved platforms is available here: https://security.utexas.edu/iso-policies/cloud-
services/decision-matrix  
 
☐ Electronic data and records will be stored on a third-party cloud service/platform that is not currently 
approved for research data storage by UT Austin’s Information Security Office (ISO) and requires local ISO 
approval. → If this box is checked, the study team must obtain security clearance from UT Austin ISO (or Dell Med IT, if 

Page 55 of 58 
 
 
applicable) approving use of this platform to store research data for this study. UT IRB approval cannot be granted until 
documentation of ISO/IT approval has been uploaded to the study in UTRMS under “Other Attachments.” To avoid delaying 
approval, consider selecting a different option for storing data, if possible.  
 
☐ Other method(s) of storing and limiting access to electronic data and records, describe in the text box 
below:  
Examples might include use of a platform hosted and approved by a collaborating institution or sponsor for this research, 
use of non-cloud-based electronic storage methods (e.g. hard drive), etc.: 
 
 
 
 
48. Physical Materials – Storage and Access 
One of the following must be checked. 
☒ Physical data/records/specimens (e.g. signed research consent forms, paper surveys/notes, physical recordings, 
samples etc.) will be stored in a secure location with access limited only to individuals who need access for 
purposes related directly to this research study. 
 
☐ N/A – no physical materials 
49. Research Records Retention Attestation 
 
Confirm that research records will be maintained in compliance with all relevant records retention policies.  
 
UT Austin’s research record retention policy requires that data and copies of relevant study documents (e.g. consent 
forms, protocol, recruitment materials, etc.) be maintained for at least 3 years from completion of the research project. 
Note that researchers are NOT required to maintain identifiers linked to data for 3 years.  To protect confidentiality, 
identifiers can be unlinked from study data and destroyed as soon as feasible (described in the next item). UT Austin’s 
records retention policies are available here:  https://records.utexas.edu/utrrs 
 
Some research may be subject to other retention policies that require longer retention periods and retention of other 
specific data or materials (e.g. collaborating institutions, funding agencies or sponsors, FDA, HIPAA, etc.). For example, 
studies that involve use of protected health information (PHI) covered by HIPAA must retain all relevant records for at 
least 6 years. 
 
Check the box below to acknowledge the above information and confirm the study team will comply with UT Austin’s 
policy as well as any other records retention policies that apply to this research.  
 
This box must be checked.  
 
☒ Confirm 
 
 
50. Destruction of Identifiable Information 
One of the following must be checked.  
 
 
☐ No identifiable information is recorded at any point in this research.  
 
☐  Identifiable information will be destroyed. → Specify at what point in the research process identifiable 
information about participants will be destroyed. One of the following must be checked: 
☐ Upon completion of procedures requiring use of identifiers (i.e. compensation, data linkage, etc.) 
☐ After all data collection/cleaning/transcription is complete 
☐ At the time of study closure/once study is complete 
☐ Other, describe below: 

Page 56 of 58 
 
Data Sharing & Future Use 
51. Data Sharing and Future Use 
 
Check the box below that best describes your plans for use and sharing of data beyond the scope of the current research. 
You are strongly encouraged to consider the broadest possible future plans you might have. One of the following must be 
checked. 
 
☐ There are no plans to use or share data/specimens for other research purposes not related to this study. → 
skip to item 53 
 
☒ Data/specimens may be shared with other researchers or banked (by this study team or other researchers) 
for future research purposes not related to the current research. → address the following: 
 
 
52. Data Registry/Specimen Repository (Details)  
Select all that apply. 
 
☐ Contributing data/specimens to an existing registry/repository → describe this registry below; if this registry is 
maintained by UT researchers, provide the IRB Study ID# and/or the registry name and Principal Investigator responsible 
for the registry: 
 
 
 
 
 
 
 
 
☐ Creating a new registry/repository → complete the following: 
 
 
 
  
☒ Identifiable information will not be destroyed.  
If checked, explain the rationale for retaining identifiers indefinitely and specify if identifiers will remain linked to research 
data (either directly or indirectly via a code key).   
 
 
For patients enrolled, we will keep their identifiable information in case of audit readiness 
and reporting by review boards. Identifiers will be indirectly linked to the study data via a 
secure linking log that associates participant names with subject ID numbers. This log is 
necessary for data entry validation, audit trails, and regulatory compliance. It will be stored 
exclusively on UT Austin’s encrypted and access-controlled servers, and access will be 
restricted to IRB-approved study personnel. Identifiable information will not be included in 
the primary study dataset used for analysis, and all identifiers will be destroyed following 
study closeout in accordance with UT data retention policies and IRB protocol. All study 
data used for analysis will be de-identified, and the linking log will be stored separately 
from the dataset to maintain confidentiality. 
51a. Select which data sharing plans/future uses apply:  
“Coded” refers to data that is indirectly identifiable via a code key that links study ID#s back to participant 
identifiers. Ensure this aligns with the description of future use in the consent form(s), when applicable. 
☒ Anonymized data/specimens may be shared or banked for future research → skip to item 53 
☐ Coded data/specimens may be shared or banked for future research → complete section 52 
☐ Identifiable data/specimens may be shared or banked for future research → complete section 52 

Page 57 of 58 
 
 
 
52a. Describe the intended purpose and target area(s) for this registry: 
 
 
 
 
 
 
 
 
52b. Describe any options that will be provided to participants to stipulate future use of their 
data/specimens. If participants will be given the option to be contacted regarding future uses, 
describe the procedure(s) for this contact.  
Be sure to include all options and stipulations in the consent form(s). If no stipulations or future contact will be 
offered, explain this below. 
 
 
 
 
 
52c. Who will be allowed access to registry data/specimens? 
☐ Only the PI of this study and/or other members of the current study team → skip to item 53 
☐ Other researchers will be able to request data/specimens from the registry → below, describe how 
other researchers will be able to request data/specimens from the registry, what criteria will be used to approve 
such requests (e.g., IRB approval, application process), and what methods will be used to release data/specimens 
to other researchers securely: 
 
 
 
 
Conflicts of Interest 
Please confirm that all research personnel who meet the definition of “covered individuals” are designated as such in the Local Study 
Team Members section of the SmartForm application in UTRMS-IRB.  
 
53. 
Financial Conflicts of Interest 
Financial interest includes utilizing your licensed intellectual property in the study; serving as a paid consultant, or advisory 
board member, or officer/director with a related entity; and equity or business ownership in a company that is related to this 
project.  Additional guidance on financial conflicts of interest is available on the COI website. 
 
One of the following must be checked.  
 
 
 
☒ To the best of your knowledge, no one on the study team has a financial interest related to this study. 
 
☐ The PI and/or other covered individual(s) has/have a financial interest related to this study.  
             If so, please provide the name(s) of the covered individuals involved, and briefly describe the interest: 
 
 
 
 
 
54. 
Non-financial Conflicts of Interest 
Non-financial Interests could include such things as: 
- utilizing your unlicensed intellectual property in the study, 
- serving as an unpaid advisory board member or officer/director with a related entity,  
- equity or business ownership in a company that has yet to make a profit and is related to this project, 
- conflict of time/effort, 
- personal and professional relationships/affiliations, 
- personal beliefs/feelings impacting ability to conduct the study without bias, 
- any other factors that could create bias in the study  
 
One of the following must be checked.  
 

Page 58 of 58 
 
 
 
☒ To the best of your knowledge, no one on the study team has non-financial interest related to this study. 
 
☐ The PI and/or other covered individual(s) has/have a non-financial interest related to this study.  
             If so, please provide the name(s) of the covered individuals involved, and briefly describe the interest: