Conditions: Schizophrenia
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 4
Healthy volunteers: no

Brief summary:
The purpose of this study is to offer open label ITI-007 treatment to patients who poorly respond or poorly tolerate approved medications.

Detailed description:
Patients will be started on ITI-007 and current medication will be slowly discontinued within the first 7 days of starting ITI-007, with some flexibility allowed if clinically indicated. No patients will be left unmedicated because of this study.

Patients will be seen weekly for the first 4 weeks, biweekly for the second month and then monthly for six months. Patients will be monitored by clinical and safety rating scales, and will be required to show improvement after 3 months to remain in this study. Patients not improving at this time will be assessed for the risks/benefits of continuing.

Arms:
arm 1: Open-Label ITI-007 40-60 mg

Interventions: intervention 1: ITI-007
Intervention descriptions: intervention 1: ITI-007 (Lumateperone tosylate)dosed 40-60 mg based on efficacy/adverse events

Protocol document:
Prot_000.pdf: 
Protocol Summary Form
7716
Lieberman, Jeffrey
Page 1 of 10
Protocol Title:
Lumateperone for Schizophrenia
Protocol Number:
7716
First Approval:
01/23/2019
Expiration Date:
10/14/2020
Version Date:
10/16/2019
Clinic:
Leiber Research Clinic
Contact Principal Investigator:
Jeffrey Lieberman, MD
Email: jlieberman@columbia.edu
Telephone: 212-543-5300
Co-Investigator(s):
Lawrence Kegeles, MD
Joshua Kantrowitz, MD
Research Chief:
Daniel Javitt, MD, PHD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am submitting an annual continuation without modifications 
Division & Personnel
Division
What Division/Department does the PI belong to?
Experimental Therapeutics
Within the division/department, what Center or group are you affiliated with, if any? 
Lieber Clinic
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
none


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 2 of 10
Application for Continuation of Research
Status
Current Status of Study: 
Subject enrollment is ongoing.
Summary of Experiences to Date
Please provide a summary of scientific progress of the study and the experience of research participants, to 
date. This requirement is designed to allow for the investigator and the IRB to reassess the study’s risks and 
benefits in terms of developments in the field, changing practice patterns, and new IRB policies and 
procedures.
As of 8/22/19, five (5) participants have signed consent.  Out of the 5, one subject withdrew consent 
immediately after consent/capacity evaluation and did not have any screening assessments completed.  
There are two participants currently on ITI-007 (lumateperone) and one participant who started ITI-007 but 
withdrew consent after several days due to perceived side effects that were unclearly described. The fifth 
subject is currently in screening with the intention to start ITI-007 mid-September.
 
The first subject started on ITI-007 has completed 5 months of treatment thus far, and is overall improved 
despite requiring a down titration to 40 mg for insomnia and a clinically determined prolonged taper of his 
pre-study antipsychotic.   The 2nd participant currently on ITI-007 has done well through the first 3 weeks 
of treatment.
 
Funding
Have there been any changes in funding status since the prior approval? 
No
Have the principal investigator and other investigators made all required disclosures of financial interest in 
the study sponsor/product?
Yes
Summary
Have there been any study findings, recent literature, or untoward events occuring here or at other sites in 
the past year which might affect the analysis of the safety, risks or benefits of study participation? 
No
Have there been any serious adverse events (serious and/or unanticipated problems involving risks to 
subjects or others at this site which occured in the past year)? 
No
Have all study staff with a significant role in the design or implementation of the human subject components 
of this study received required training in human research subject protections?


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 3 of 10
Yes
Is the study covered by a certificate of confidentiality? 
No
Overall Progress
Approved sample size
40 enrolled, 30 completed
Total number of participants enrolled to date
5
Number of participants who have completed the study to date 
0
Have there been any significant deviations from the anticipated study recruitment, retention or completion 
estimates? 
No
Comments / additional information 
Sample Demographics
Specify population
schizophrenia/schizoaffective
Total number of participants enrolled from this population to date 
5
Gender, Racial and Ethnic Breakdown 
Male: 5
Female: 0
 
White: 3
Black: 0
Asian: 1
Other/Unknown: 1
 
Hispanic: 0
Non-Hispanic: 5 
 
Summary of Current Year's Enrollment and Drop-out 
Number of participants who signed consent in the past year
5
Number of participants currently enrolled
3
Did the investigator withdraw participants from the study? 


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 4 of 10
No
Did participants decide to discontinue study involvement? 
Yes
Circumstances of discontinuation:
One participant withdrew consent immediately after consent/capacity evaluation. No screening procedures 
were initiated.
 
One participant withdrew  after several days of treatment with ITI-007 due to perceived side effects that 
were unclearly described.
Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Medication Trial
   Use of Investigational Drug or Device
Population
Indicate which of the following populations will be included in this research
   Adults over 50
   Individuals with Psychosis
Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract application is a pending review or a funding decision
Source of Funding


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 5 of 10
Industry
Sponsor
Intra-Cellular Therapies
Is the study investigator initiated? 
Yes
Select one of the following
Single Site
Business Office
RFMH
Does the grant/contract involve a subcontract? 
No
Study Location
Indicate if the research is/will be conducted at any of the following
   NYSPI
This protocol describes research conducted by the PI at other facilities/locations
No
Uploaded Protocol Summary Form
Upload Document
Select file to upload.
lumateperone PSF 10.7.19.pdf
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
An urgent need exists for new treatments of schizophrenia that are effective against a broad range
of symptoms and free of limiting safety issues.ITI-007 (Lumateperonetosylate)is an experimental 
medication that affects brain proteins that is being developed as a schizophrenia treatment. ITI-007 appeared 
to work similarly to an FDA approved medication for schizophrenia (risperidone) in a recently published 
study (Lieberman et al 2016 : see attached). The purpose of this study is to offer open label ITI-007 
treatment to patients who either poorly respond or poorly tolerate approved medications. A discussion about 
clozapine will occur during the consent process. 
 
In this study, subjects will be started on ITI-007. Current antipsychotic medication will be slowly 
discontinued within the first 7 days of starting ITI-007, with some flexibility allowed if clinically indicated. 
No subjects will be left unmedicated because of this study.


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 6 of 10
 
Subjects will be seen weekly for the first 4 weeks, biweekly for the second month and then monthly for six 
months. Subjects will be monitored by clinical and safety rating scales, and will be required to 
show improvement after 3 months to remain in the study. Subjects not improving at this timewill be 
assessed for the risks/benefits of continuing.
Description of Subject Population
Sample #1
Specify subject population
schizophrenia/schizoaffective
Number of completers required to accomplish study aims
30
Projected number of subjects who will be enrolled to obtain required number of completers
40
Age range of subject population
18-60
Gender, Racial and Ethnic Breakdown
Based on the Epidemiologic Catchment Area Survey (Regier et al, Acta Psychiatr Scand 1993
attached), along with a more recent publication (Bresnahan et al, Int. J. Epidemiol, 2007 attached),
we have revised our demographics section. The rates differ in other countries, but we have limited our
response to the United States.
The demographics of schizophrenia in the United States are ~ 1% of the population of each ethnicity,
with the exception of more men (ratio 1.4:1) and a 2 to 3 fold increased rate in African Americans. Of
note, some studies suggest that people of African ancestry are just over diagnosed (Strakowski J Clin
Psych 1993).
The literature supports that the demographics of schizophrenia in any specific area, such as New
York City in general, and Washington Heights specifically should reflect the demographics of the
area (see Reiger 1993). For example, Washington Heights has a large percentage of Hispanic people
with schizophrenia because of the relatively large number of Hispanic people in Washington Heights.
Thus we anticipate oversampling a Hispanic population relative to the US, and will increase outreach
to other ethnicities if this happens.
The following is a gender and ethnic breakdown for the US population as of 2014, modified to reflect
the demographics of schizophrenia (e.g. we increased the number of males to reflect a 1.4 to 1 ratio,
and double the percentage of African Americans (13% of US->26%) and reduced the number of
white's by 13% to make up the difference):
https://www.census.gov/quickfacts/table/PST045215/00.
 
Gender: 
Male/female: 60/40%


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 7 of 10
 
 Race:
White: 54%
Black 26%
Asian 5%
Other 15%
 
Ethnicity: 
Hispanic (all races) 17%
Non-hispanic: 83%
Description of subject population
DSM-V diagnosis of schizophrenia or schizoaffective disorder who failed to show an adequate response in 
the level of psychotic symptoms to current antipsychotic or poorly tolerating current antipsychotic
Recruitment Procedures
Describe settings where recruitment will occur
Patients will be recruited from the Lieber Center under IRB protocol #6991.
Recruitment will also occur at the Washington Heights Community Service outpatient clinics.
All recruitment material will be approved by the local IRB prior to distribution.
 
Additionally, a description of this study will be posted on Columbia University Medical Center RecruitMe 
website. RecruitMe is a recruitment tool meant to connect those who what to participate in clinical trials to 
the researcher that are conducting them.  Interested individuals will be contacted by study staff to deem if 
potentially eligible.  If potentially eligible, a visit will be scheduled to have the participant sign consent and 
undergo screening procedures.
 
A description will also be listed on NAMI Metro's website: https://www.naminycmetro.org/get-
involved/research-studies/ 
 
 
How and by whom will subjects be approached and/or recruited? 
We will follow the IRB approved recruitment plan of IRB protocol #6991.
Study staff will visit the WHCS clinics to present the study to clinicians and patients, including distributing
and posting the IRB flyer approved for this study.
 
Interested individuals who hear about this study from the RecruitMe or NAMI Metro websites will contract 
research staff listed on the postings to hear more about the study.  If potentially eligible, interested 
individual will be scheduled for a consent and screening visit. 
How will the study be advertised/publicized? 


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 8 of 10
Word of mouth and advertisements. The trial will be listed on clinicaltrials.gov.  The research study will also be listed on CUMC 
RecruitMe and NAMI Metro websites.
Do you have ads/recruitment material requiring review at this time? 
Yes
Does this study involve a clinical trial?
Yes
Please provide the NCT Registration Number
NCT03817528
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
Yes
Describe concurrent research involvement
Subjects may be recruited through the Lieber Clinic screening protocol-IRB #6991. Subjects will be permitted to participate in other 
projects that do not exclude experimental medications on a case by case basis.
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
No
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
Yes
Indicate NYSPI IRB # 
6991
Describe Study Consent Procedures
Potential subjects from the WHCS clinics (Inwood and Audubon) may have their chart reviewed under 
IRB Protocol #6991 to see if he/she may be eligible for the current study. Please note that subjects will 


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 9 of 10
still consent to the current protocol and undergo screening procedures of this protocol to be determined 
eligible for the study.
The chart review under IRB #6991 will allow our staff to identify subjects who MAY be eligible for the
current study. As detailed in #6991, potentially eligible subjects will be contacted as described in the
procedures outlined previously to hear about the study and decide if he/she is interested in participating.
Indicate which of the following are employed as a part of screening or main study consent procedures
   Consent Form
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Kantrowitz, Joshua, MD
Kegeles, Lawrence, MD
Type in the name(s) not found in the above list
Independent Assessment of Capacity
You have indicated that your study involves subjects who MAY LACK capacity to consent.
Does this study require an independent assessment of capacity?
Yes
Methods/procedures for capacity assessment
An independent psychiatrist will assess the subject's capacity to provide informed consent. If a subject has 
difficulty understanding all study elements during the consent process, the procedures will be explained 
again by a member of the research team. If there is still doubt about the subject's understanding of the 
key elements of the study and ability to provide informed consent, the subject will not be enrolled in the 
study.
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
   Drug
Select the number of drugs used in this study
1
Drug #1
Name of the drug 
Lumateperone tosylate (ITI-007) 
Manufacturer and other information
Intracellular Therapies
Approval Status


Protocol Summary Form
7716
Lieberman, Jeffrey
Page 10 of 10
IND is approved
IND#
141741
Who holds the IND/IND sponsor?
IND is held by PI/CU Investigator
Lieberman, Jeffrey, MD
Methods to Protect Confidentiality
Will the study be conducted under a certificate of confidentiality?
No
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
We will not be compensating participants for the study, but we will provide reimbursement for study related 
expenses (e.g., travel, meals, etc) up to $50. You may be asked to provide receipts for reimbursement of 
expenses.
Uploads
Upload the entire grant application(s)
Upload copy(ies) of unbolded Consent Form(s)
ITI-007 -clean 8.21.19.pdf
Upload copy(ies) of bolded Consent Form(s)
Upload copy(ies) of recruitment materials/ads to be reviewed
Lumateperone Research Participant Post (for NAMI).pdf
Luma Columbia RecruitMe.pdf
ITI-007 flyer 5.16.19.pdf
Upload evidence of FDA IND approval(s)
Upload copy(ies) of the HIPAA form
7716_HIPPA_Authorization.pdf
Upload any additional documents that may be related to this study


 
             Uploaded Protocol Summary Form 
 
Cover Page 
 
Protocol Number: 
7716  
     Version Date: 10/7/19 
Protocol Title: ITI-007 (Lumateperone tosylate) for schizophrenia 
Principal Investigator: Jeffrey A. Lieberman, M.D. contact PI) 
Email: Jeffrey.Lieberman@nyspi.columbia.edu 
Telephone: 646-774-5300 
Office: PI Chair office                                   Cell Phone: N/A 
 
Lay Summary 
This section is intended to provide a basic overview of the study including a description of its purpose, methods, and 
subject population.  The summary should provide a concise overview of the study for non-scientific and scientific 
members of the IRB.  Please avoid medical or technical terminology.  In general, the abstract of a grant does not provide 
a suitable lay summary. 
Please also paste of a copy of the Lay Summary into the PRISM PSF Form. 
An urgent need exists for new treatments of schizophrenia that are effective against a broad range 
of symptoms and free of limiting safety issues. ITI-007 (Lumateperone tosylate) is an experimental medication 
that affects brain proteins that is being developed as a schizophrenia treatment. ITI-007 appeared to work 
similarly to an FDA approved medication for schizophrenia (risperidone) in a recently published study 
(Lieberman et al 2016 : see attached). The purpose of this study is to offer open label ITI-007 treatment to 
patients who either poorly respond or poorly tolerate approved medications. A discussion about clozapine will 
occur during the consent process.  
 
In this study, subjects will be started on ITI-007. Current antipsychotic medication will be slowly discontinued 
within the first 7 days of starting ITI-007, with some flexibility allowed if clinically indicated. No subjects will 
be left unmedicated because of this study. 
 
Subjects will be seen weekly for the first 4 weeks, biweekly for the second month and then monthly for six 
months. Subjects will be monitored by clinical and safety rating scales, and will be required to show 
improvement after 3 months to remain in the study. Subjects not improving at this time will be assessed for the 
risks/benefits of continuing. 
Background, Significance, and Rationale 
In this section, provide a brief summary of the status quo of the relevant work field, and how the proposed study will 
advance knowledge. Specifically, identify the gaps in knowledge that your project is intended to fill. If no gaps exist that 
are obviously and directly related to your project, explain how your proposed research will contribute to the overall 
understanding of your field. Describe potential impacts of your project within your field of study and in a broader context. 
Provide a critical evaluation of existing knowledge. The literature review does not have to be exhaustive.  


 
             Uploaded Protocol Summary Form 
 
Schizophrenia is a severe, complex, chronic, and disabling psychiatric disorder with a lifetime prevalence of 
around 1%. 
Numerous antipsychotics have been developed which all rely on the same underlying mechanism, namely 
interfering with dopamine receptors, and more specifically, dopamine D2 receptor antagonism. Therapies 
with phenothiazines, such as haloperidol and thiothixene, are effective but induce extra pyramidal 
symptoms (EPS) such as dystonia, muscle rigidity, tremor, and akathisia. Other medications, such as “atypical” 
or “second generation antipsychotics,” may have less EPS, but are more prone to induce weight gain or 
metabolic side effects such as increased cholesterol or diabetes. Long-term effects, which develop after months 
to years of therapy, also include tardive dyskinesia. The adverse effects appear to be directly related to the 
dopamine D2 receptor blockade in the basal ganglia, whereas the antipsychotic effect of these compounds is 
dependent on reducing dopamine D2 mediated neurotransmission in the mesolimbic tracts (including the 
nucleus accumbens, stria terminalis, and the olfactory tubercle).  
Clozapine is the most efficacious antipsychotic, yet is among the most prone to the aforementioned metabolic 
disturbances. It is also associated with an increased incidence of seizures and potentially lethal side effects of 
agranulocytosis and myocarditis. Consequently, there is tremendous unmet medical need for safer treatments 
that are more effective and have a broader spectrum of efficacy across multiple symptom 
domains. 
 
ITI-007 (Lumateperone tosylate) is a new molecular entity with a unique pharmacologic profile that combines 
dose-related monoamine modulation with phosphorylation of intracellular signaling proteins (Lieberman et al 
2016 : see attached).  While it interacts with several targets that are common to some existing antipsychotics, its 
full actions are complex and unique (Snyder 2015). ITI-007 is a high-affinity serotonin 2A (5-HT2A) receptor 
antagonist with lower, but clinically relevant, affinity for other neurobiological targets, including D2 receptors. 
While 5-HT2A receptor antagonism in addition to D2 receptor antagonism has been the hallmark of atypical 
antipsychotics (Meltzer 1989), ITI-007 has a wider separation (sixtyfold) between its affinity for 5-HT2A 
receptors and D2 receptors than other antipsychotics, allowing full saturation of 5-HT2A receptors, even at 
modest levels of dopamine receptor occupancies (Snyder 2015). Moreover, unlike most other antipsychotics 
that are antagonists at D2 receptors both presynaptically and postsynaptically, and unlike aripiprazole and 
related compounds that are partial agonists at D2 receptors both presynaptically and postsynaptically, ITI-007 
interacts with dopamine receptors in a unique way. At D2 receptors, ITI-007 is a presynaptic partial agonist and 
postsynaptic antagonist with functional mesolimbic/mesocortical selectivity (Snyder 2015). This allows for 
functional blockade of dopamine without increasing dopamine turnover and corresponds to antipsychotic 
efficacy without motor side effects (Snyder 2015). Above and beyond 5-HT2A and D2 receptor interactions, 
ITI-007 increases phosphorylation of mesolimbic GluN2B subunits of N-methyl-D-aspartate (NMDA) receptors 
(Snyder 2015). An increase in GluN2B increases synaptic NMDA activity via subcellular trafficking to plasma 
membranes (Goebel-Goody 2009). To the extent that a deficit in glutamatergic function contributes to 
schizophrenia symptoms (Laruelle 2005, Javitt 2007), indirect enhancement of glutamatergic 
NMDA function is predicted to reduce psychosis and improve cognitive function and negative symptoms. 
Although investigational therapeutics targeted solely at direct interaction with glutamate receptors or glycine 
transporters have not successfully translated into clear clinical benefit, it is recognized that the interaction 
between glutamate and dopamine modulation is important in schizophrenia (Schwartz 2012). At serotonin 
transporters, ITI-007 inhibits the serotonin transporter (Snyder 2015), an effect associated with many 
antidepressant drugs (13). ITI-007 lacks significant activity at many receptors (e.g., H1, muscarinic, serotonin 
2C) that are associated with deleterious effects experienced with many other antipsychotics (i.e., clinically 
significant sleep induction, cognitive impairment, weight gain). Thus, by acting through serotonergic, 
dopaminergic, and glutamatergic signaling systems in a mechanistically and neuroanatomically selective 


 
             Uploaded Protocol Summary Form 
 
manner, ITI-007 represents a novel approach to the treatment of schizophrenia and other neuropsychiatric 
disorders. 
 
In a recently published study (Lieberman 2016),  ITI-007 was effective and safe for the treatment of 
schizophrenia and comparable with placebo with regard to safety.  
 
This was a phase II randomized, double-blind, placebo-controlled, and active-controlled trial conducted at eight 
sites in the United States with randomization of 335 acutely psychotic adults with schizophrenia. ITI-007 (60 
mg and 120 mg), placebo, and risperidone, included for assay sensitivity, were evaluated as monotherapy for 4 
weeks. 
The primary outcome measure was the Positive and Negative Syndrome Scale total score, with secondary 
analyses conducted on symptom subscales. 
 
ITI-007 60 mg (p=0.017, effect size=0.4) and risperidone (p=0.013, effect size=0.4) demonstrated antipsychotic 
efficacy superiority over placebo on the primary end point. The results of secondary analyses reflected 
improvements in depressive symptoms by ITI-007 60 mg. ITI-007 120 mg did not separate from placebo, and 
had higher rates of adverse events. ITI-007 60 mg was well tolerated in this patient population, as evidenced by 
low discontinuation and adverse event rates, and were associated with a benign metabolic profile as evidenced 
by significantly lower levels of prolactin, fasting glucose, total cholesterol, and triglycerides than risperidone. 
 
In not yet published studies, ITI-007 has been studied in 2 large, Phase  3 adequate, well-controlled studies in 
patients with exacerbated schizophrenia (Studies ITI-007-005, ITI-007-301, ITI-007-302). Efficacy of ITI-007 
on the primary endpoint, with statistically significant greater reductions from baseline to study endpoint (Week 
4) in PANSS total score compared to placebo, has been demonstrated in Study ITI-007-005 and Study ITI-007-
301. In all 3 studies, progressive improvement across treatment days was seen in the PANSS total score from 
baseline to Week 4, with continued improvement from baseline seen between Weeks 4 and 6 in Study ITI-007-
302. Supportive data from the Study ITI-007-301 provide evidence of pharmacological activity and clinical 
benefit from ITI-007 40 mg. 
 
In conclusion, the mechanistically novel investigational drug ITI-007 was effective for the treatment of 
schizophrenia and comparable with placebo on safety measures in these trials. Secondary analyses indicated 
that ITI-007 improved schizophrenia symptoms and might have expanded therapeutic efficacy in comparison 
with current antipsychotic drugs. 
 
The purpose of the present, open label study is to offer open label treatment to patients who either poorly 
respond or poorly tolerate approved medications. A discussion about clozapine will occur during the consent 
process. All this subjects will be made aware that clozapine may be the FDA approved treatment of choice for 
them. 
 
In this open label study, subjects will be seen weekly for the first 4 weeks, biweekly for the second month and 
then monthly for total duration of six months. Subjects will be monitored by clinical and safety rating scales.  
Subjects will be required to show a CGI improvement scale of at least 3 after 3 months to remain in the study. 
Subjects not meeting this criteria will be assessed for the risks/benefits of continuing (see criteria for early 
discontinuation section for details). 
 
Lieberman JA, Davis RE, Correll CU, Goff DC, Kane JM, Tamminga CA, Mates S, Vanover KE. ITI-007 for 
the Treatment of Schizophrenia: A 4-Week Randomized, Double-Blind, Controlled Trial. Biological 
psychiatry 2016; 79(12): 952-61. 
 


 
             Uploaded Protocol Summary Form 
 
Snyder GL, Vanover KE, Zhu H, Miller DB, O’Callaghan JP, Tomesch J, et al. (2015): Functional profile of a 
novel modulator of serotonin, dopamine, and glutamate neurotransmission. Psychopharmacology (Berl) 
232:605–621. 
Meltzer HY, Matsubara S, Lee JC (1989): Classification of typical and atypical antipsychotic drugs on the basis 
of dopamine D-1, D-2 and serotonin2 pKi values. J Pharmacol Exp Ther 251:238–246. 
Goebel-Goody SM, Davies KD, Alvestad Linger RM, Freund RK, Browning MD (2009): Phospho-regulation 
of synaptic and extrasynaptic N-methyl-d-aspartate receptors in adult hippocampal slices. 
Neuroscience 158:1446–1459. 
Laruelle M, Frankle WG, Narendran R, Kegeles LS, Abi-Dargham A (2005): Mechanism of action of 
antipsychotic drugs: From dopamine D(2) receptor antagonism to glutamate NMDA facilitation. Clin Ther 27 
(suppl A):S16–S24. 
Javitt DC (2007): Glutamate and schizophrenia: Phencyclidine, N-methyl-D-aspartate receptors, and dopamine-
glutamate interactions. Int Rev Neurobiol 78:69–108. 
Schwartz TL, Sachdeva S, Stahl SM (2012): Glutamate neurocircuitry: Theoretical underpinnings in 
schizophrenia. Front Pharmacol 3:195. 
Meyer JH (2007): Imaging the serotonin transporter during major depressive disorder and antidepressant 
treatment. J Psychiatry Neurosci 32:86–102. 
Specific Aims and Hypotheses 
Concisely state the objectives of the study and the hypothesis or primary research question(s) being examined.  There 
should be one hypothesis for every major study procedure or intervention.  For pilot studies, it is important not to 
overstate the study's objectives.  If there are no study hypotheses, describe broad study goals/aims. 
To assess safety and efficacy of open label ITI-007 40-60 mg in patients who either poorly respond or poorly tolerate 
approved medications.  
Inclusion/Exclusion Criteria 
This section details your study sample(s) and addresses the requirement for risk minimization. 
You may choose to divide your sample by population (healthy controls vs. subjects) or by procedure (subjects who will 
have an MRI) and then define different sets of criteria for each. 
For each sample, create or insert a table to describe detailed criteria for study inclusion and exclusion and the method 
you will use to ascertain each criterion. The method of ascertainment may describe tests, scales and instruments.  When 
relevant, indicate the level of training of the person who will make the assessment (e.g. clinical interview by a 
psychiatrist). 
Inclusion/Exclusion Criteria needs to be numbered and listed in outline form (see Table template below). 
 
CRITERION                                             METHOD OF ASCERTAINMENT            
Inclusion: 
 
1. Age between 18-60 
Self-report 
2. DSM-V diagnosis of schizophrenia or 
schizoaffective disorder 
 
 
SCID 
 


 
             Uploaded Protocol Summary Form 
 
3. Has capacity to provide informed 
consent 
Physician evaluation 
4. Medically stable for study 
participation 
Medical history, physical examination 
and screening laboratory parameters, 
information from clinical team, review 
of medical record. 
5. Judged clinically not to be at 
significant suicide or violence risk. 
The Columbia Suicide Severity Rating 
Scale (C-SSRS); clinical interview 
6. Inadequate response or tolerability 
to previous antipsychotic therapy, as 
defined by at least one of the following: 
prior clozapine failure, a PANSS >80 
despite at least six weeks of current 
antipsychotic therapy, a CGI-I of 4 or 
greater after at least two six week trials 
of antipsychotics (retrospective 
assessment) or failure to tolerate an 
adequate dose of at least two 
antipsychotics (as defined by the PDR). 
PANSS, CGI, medical history, including a 
discussion of the risks/benefits of clozapine 
 
CRITERION                                    METHOD OF ASCERTAINMENT                
Exclusion: 
 
1. Substance abuse within last 90 
days 
 
Physician evaluation/Urine toxicology screen 
2. ECG abnormality that is clinically 
significant, known personal or 
family history of prolonged QTc 
(>500)  
ECG reviewed by study cardiologist 
3. Pregnancy, lactation, or lack of use 
of effective birth control 
Instructions to study subject, pregnancy tests 
as per protocol and review of the medical 
record. 
4. Presence or positive history of 
significant unstable medical or 
neurological illness (including any 
history of seizure disorder, dementia, 
traumatic brain injury, untreated 
syphilis, hepatitis B/C, renal 
insufficiency or mental retardation), 
history of HIV, neuroleptic malignant 
syndrome, serotonin syndrome or 
retinal degeneration or retinal 
pigmentation/deposits 
Medical history, Ophthalmologic exam  
5. Clinically significant abnormal 
laboratory tests, positive for hepatitis B 
or C or LFT’s > 2x ULN, use of strong 
CYP3A4 inhibitors or inducers 
(appendix A). 
Screening labs 


 
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6. History or presence of concomitant 
major psychiatric illness. 
SCID 
7. Use of other antipsychotic 
medications at baseline. 
Physician evaluation 
8. Use of another investigational 
medication in the previous 4 weeks. 
Physician evaluation 
 
 
Study Procedures 
Provide a clear, concise narrative of study procedures with special attention to the subjects' involvement.  Detail the 
overall study timeline and location of study procedures, list all interventions, assessments and interviews, estimate the 
duration of each procedure, provide dosing schedules, identify study personnel involved in each procedure, and provide 
credentials for relevant personnel.  For complicated study designs, we strongly encourage attaching tables, flow-charts, 
and study algorithms. 
Screening  
Subjects must give written informed consent to participate prior to the initiation of any study procedure.   
"Screening" is defined as the pre-study assessments to determine subject eligibility for entry into the study, made within 
30 days of the first treatment visit. If screening examinations show any disqualifying abnormality, the subject will be 
excluded from participation in the study. In the case of laboratory abnormalities, the examination may be repeated up 
to one time. If the investigator wishes to include a subject with a laboratory value outside normal range, a comment 
(stating that these lab values are not clinically significant) must appear on the CRF.  
Subjects will have a clinical interview to confirm that they have an eligible psychiatric diagnosis, a physical of the eyes, 
nose, ears, mouth, heart, lungs, abdomen, and nervous system, temperature, blood pressure, pulse, and breathing rate, 
height, weight, electrocardiogram, laboratory safety tests including hematology: hemoglobin, hematocrit, RBC count, 
RBC with differential counts and percentages, platelet count, activated partial thromboplastin time, prothrombin time 
(expressed as INR); Biochemistry: lipid panel, prolactin, CPK, magnesium, phosphorus, thyroid panel, amylase, lipase, 
sodium, potassium, total protein, albumin, total bilirubin, AST, ALT, alkaline phosphatase, gamma-GT, troponin, 
cholesterol, creatinine, BUN(urea-N), glucose, and uric acid; urinalysis: pH, glucose, protein, bilirubin, urobilinogen, 
nitrite, leukocytes and erythrocytes.  A midstream urine sample (approx. 30 mL) will be obtained in order to avoid 
contamination and allow a proper assessment; drug screen for any substances of abuse (e.g., amphetamines, cocaine, 
morphines, marijuana) hepatitis screen: for hepatitis B surface antigen (HBsAg) hepatitis C will be based on HCV 
antibodies, serum pregnancy test: βHCG results will be collected for all women.  Subjects will be asked medical/health 
history and will be assessed for any incidental medical symptoms or medical complaints such as headache; dizziness; 
nausea; sleepiness; visual, hearing, taste, or smell changes; urinary symptoms; chest, limb, back, joint, or abdominal 
pain; rashes; itching; and shortness of breath.  
A discussion about clozapine will occur during the consent process, and the reasons for not beginning clozapine 
will be documented in the chart. All this subjects will be made aware that clozapine may be the FDA approved 
treatment of choice for them. 
 
d. Study Procedures 


 
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Treatment period 
 
In this open label study, subjects will be seen weekly for the first 4 weeks, biweekly for the second month and 
then monthly for total study duration of six months. Subjects will be monitored by clinical and safety rating 
scales (PANSS, side effects checklist, CGI severity and improvement, AIMS, BARS and SAS and C-SSRS: 
Biweekly for the 1st six weeks and then monthly), and will be required to show a CGI improvement scale of less 
than 4 after 3 months to remain in the study. Subjects not meeting this criteria will be assessed for the 
risks/benefits of continuing (see criteria for early discontinuation section). 
 
Clinical labs (blood draws), Vitals, neurological exam, and ECG will be done Biweekly for the 1st six weeks and then 
monthly. Urine pregnancy tests will be done at screening, prior to 1st dose and then monthly. 
Each visit is expected to take 1 to 2 hours. 
Unscheduled clinical evaluations may occur at any time if deemed appropriate by the Investigator in order to 
follow up on safety and/or adherence or discontinue patient participation. An unscheduled assessment may be 
performed to evaluate for the presence of other antipsychotic drug(s). 
Dosing: Patients will be instructed to take ITI-007 60 mg once daily in the evening (QPM). To improve tolerability, 
patients may be instructed to take the study treatment with food. Subjects may be up or down titrated within a 
range of 40 to 60 mg for efficacy or adverse effects. Any patient not tolerating the study treatment should be 
discontinued and started on standard of care medication. Study treatment may be discontinued at any time at the 
discretion of the Investigator or upon withdrawal of consent by the patient. 
Ophthalmologic exam: Patients will receive an ophthalmologic exam  by an ophthalmologist (for retinal 
degeneration or pigmentation/deposits) at baseline and at the conclusion of the study (6 months). The exam 
will include a standard evaluation, and an optical coherence tomography (OCT) and visual field exams 
Concomitant Medications:  
There is no washout or medication free period required for this study.  
Subjects will not be permitted to remain on pre-study antipsychotics in this study. All pre-study antipsychotics will 
be discontinued by the study physician as clinically indicated (e.g. taper/abrupt discontinuation). Current 
antipsychotic medication will be down-tapered within the first 7 days of this treatment Period, with some flexibility 
allowed if clinically indicated. Subjects will be started on ITI-007 during the cross taper period, and no subjects will 
be left unmedicated because of this study. 
All other medications, including other psychotropics, will be continued as clinically indicated. Subjects receiving 
serotonin modulating medications and benzodiazepines (and other sedating medications) will be monitored for 
excessive sedation at every visit with the side effect checklist.  
Coordination with outside providers: 
All subjects not receiving care at the Lieber Schizophrenia clinic will be asked to sign a release to contact their current 
community psychiatrist or therapist prior to enrollment. The community psychiatrist or therapist will be updated on the 
status of the subject prior to enrollment, at the beginning and end of each treatment period and upon study completion. 


 
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The outside provider will be provided with the 24 hour contact for the study physician. These updates will be 
documented in the study chart.   
End of Participation 
Care at termination of the study will transfer back to their previous providers. 
If ITI-007 becomes commercially available during this study, the trial may be discontinued.  
 
If subjects are hurt by the study their medical care will be provided, but their insurance will be billed for the care.   Any 
relevant health information revealed during the study will be shared with the subject or their health care provider at the 
subject’s request.  
 
Criteria for Early Discontinuation 
Define criteria that will be used to exit or drop subjects from the study.  Indicate the time points when such criteria will be 
applied, and describe the rating instruments, parameters, and thresholds that will lead to a decision to terminate a 
subject's participation.  In addition, explain procedures for managing subjects who are dropped from the protocol. 
For treatment studies: To minimize risks to subjects, operationalized drop-out criteria should be defined so that subjects 
who worsen, or in some cases, fail to improve, are removed from the study and offered standard care.  The threshold for 
drop-out should consider the level of risk associated with non-improvement for the specific disorder, the availability of 
alternatives, and the typical required duration of treatment.  For example, emergence of suicidal intent, or psychosis, 
should prompt immediate clinical evaluation and withdrawal from the study. 
After three months, we will conduct a clinical evaluation that considers both schizophrenia symptoms (CGI-I) 
and side effects and tolerability of the medication.   
For symptom improvement, we will require a CGI-I of at least 3.  We considered requiring a CGI of at least 2, 
but with the revised stricter I/C criteria, we feel that even a CGI of 3 is clinically meaningful. For subjects 
without a CGI-I of at least 3, they will be assessed for the risks/benefits of continuing. Medication tolerability 
and patient preference for continuing will be evaluated at this time, and subjects could remain in the study 
after 3 months with a CGI of 4 with improved tolerability.  Subjects with a CGI-I of >4 will be removed.  
Regardless of CGI status, all subjects will be verbally re-consented at three months, with a capacity assessment 
by an independent psychiatrist, and this evaluation will include a discussion of clozapine.  
 
Stopping Rules 
The study stopping criteria are well defined and are listed below: 
A subject will not receive any further doses of the study drug should any of the following events occur: 
- Any serious adverse event.  If drug relationship can be ruled out (e.g., hospitalization due to traumatic injury),  no 
decisions will be taken for the study as a whole. 


 
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- Liver function tests values above the following limits: 
• 
ALT or AST above 3xULN 
• 
Alkaline phosphatase or total bilirubin above 1.5Xuln 
- Prothrombin time expressed as INR >1.3 
- An increase of creatinine of more than 35% from the individual baseline value. 
- Decrease in Hemoglobin by more than 2 mg/dL. 
- QTc (Fridericia) longer than 500 msec or increasing by more than 60 msec from the individual baseline value confirmed 
by a second ECG after at least 5 minutes rest. 
- Changes by more than 40 mm Hg in systolic blood pressure, by more than 20 mm Hg in diastolic blood pressure or 
blood pressure equal or above 180 mm Hg systolic or 110 mm Hg diastolic. Values should be confirmed by a second 
measurement after at least 5 minutes rest. 
- Symptomatic orthostatic hypotension. Values should be confirmed by a second measurement after at least 5 minutes 
rest. 
- Any other physical examination finding, change in vital signs, adverse event, or laboratory abnormality that in the 
opinion of the Investigator would cause an excessive risk if the subject continued the study. 
A subject will be discontinued from the study and not receive any further dose of study medication if a CGI-
improvement (CGI-I) score of 6 or 7  or a C-SSRS of 4 or 5 at anytime.  
 
 
Blood and other Biological Samples 
Describe how the sample will be used and indicate, when relevant, the amount of the sample.  The IRB wants to know 
that the sample is sufficient for the purposes of the study, but that sampling is limited to what is minimally necessary.   
If you’ve indicated that you intend to store a sample for future use, indicate where the sample will be stored, how long 
the sample will be stored, and to what purposes the sample will eventually be put.  Check the IRB website at 
http://irb.nyspi.org/irbdnn/Policies/GeneticResearch/tabid/96/Default.aspx   for specific guidance and additional 
information about future use of DNA samples. 
Approximately 200 mL of blood (equal to 13.5 tablespoons) will be drawn during the entire study on different days, no 
more than one tablespoon at a time.  
Assessment Instruments 
List all assessment instruments, indicate who will administer them, and provide an estimate the duration of each.  The 
IRB wants to know that assessments instruments are appropriate measures for the purposes of the study and are no 
more burdensome than is necessary.  The IRB will consider the burden of assessment instruments (in terms of time, 
sensitivity of material, etc.) in the risk/benefit analysis.  Please attach copies or otherwise provide all non-standard 
instruments. 


 
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CGI-S/CGI-S: 5 minutes 
SCID: 1 hour 
PANSS: 30 minutes 
C-SSRS ratings:10 minutes 
BARS: 5 minutes 
SAS: 5 minutes 
AIMS 5 minutes 
Research Related Delay to Treatment 
Research involving participants who are in need of treatment invariably involves delay to care, and this delay is 
associated with risk.  Scheduling of procedures must be carefully organized to minimize delay.  Other delay must involve 
only that minimally necessary to accomplish the aims of the research while respecting subject well- being and safety. 
Describe the delay, by virtue of research participation in this study, before a participant can receive treatment of known 
efficacy or standard care routinely offered in the community. 
This is an investigational product that is not a proven effective treatment, and if you complete the full study, it will be at 
least six months before a subject will receive FDA approved treatment. Patients will be considered for removal if there is 
no benefit after 3 months.  
Clinical Treatment Alternatives 
Describe what other treatment or assessment options are available to subjects who do not participate in research. 
Subjects have the option to be on other available antipsychotic medications outside the study. The consent 
process will include a discussion of clozapine. 
Risks/Discomforts/Inconveniences 
"Risk" is a broad term used to convey the potential for harm, burden, and inconvenience related to research 
participation.  Use this section to provide a comprehensive description of foreseeable physical, psychological, social, 
interpersonal, and economic risks introduced by the research.  Include the source of the information.  Consider both the 
probability and magnitude of harm and its impact.  Describe the foreseeable harms associated with the research 
(untoward effects of a medication) and those related to delay to individualized treatment.  Include data from the 
literature, and local data, if available, on risk rates and subject experiences with research procedures. Describe 
procedures in place to minimize risk. In general, please create a numbered list of risks/categories of risk, and in general 
put the list in the order of significance or level of risk, the most significant risks first followed by others.  
In addition to specific risks of ITI-007, subjects may worsen from discontinuing their baseline antipsychotics. 
Safety and Efficacy in Humans 
ITI-007 is an experimental drug which is not approved by the FDA. In research studies already conducted with 
ITI-007 in the U.S. and in other countries, over 1,500 people have received ITI-007.  This includes 
approximately 700 people at a dose of at least 60 mg in ongoing studies and approximately 100 people at 120 
mg. 


 
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People have not been exposed to ITI-007 for longer than 42 days in completed studies.  A one-year study is 
ongoing but not complete. 
The most frequent side effects observed with ITI-007 administered up to 42 days include: 
• 
Headache 
• 
Tiredness or sleepiness 
• 
Dizziness or lightheadedness 
Summary of side effects: 
Oral doses up to and including 140 mg once daily for 5 days, up to and including 120 mg administered once 
daily for 28 days, and up to and including 60 mg once daily for 6 weeks have been administered to patients 
with schizophrenia. Doses of 9 mg once daily for 7 days have been administered to patients with dementia. ITI-
007 has been well tolerated in across this broad range of doses. 
A total of 1431 subjects have been exposed to ITI-007 in the completed clinical trials; 763 of these 1431 
subjects (53.3%) have experienced at least 1 TEAE. The most commonly reported TEAEs (reported in ≥5% of 
subjects) have been headache, somnolence, sedation, nausea, dry mouth, and dizziness (Table). 
Table: Treatment-Emergent Adverse Events Reported in 5% or More of Subjects in 
Completed Clinical Studies 
 
 
Additional adverse events that have been reported in ≥2% of subjects include constipation (3.5%), diarrhea 
(3.4%), blood CPK increased (3.1%), insomnia (2.5%), dyspepsia (2.4%), vomiting (2.2%), and orthostatic 
hypotension (2.0%). 
Most TEAEs have been non-serious and have not led to discontinuation of ITI-007. Of the 1431 subjects who 
have been exposed to ITI-007 in completed clinical trials of patient populations, 57 subjects (4.0%) have 
discontinued treatment with ITI-007 because of adverse events. Adverse events that resulted in discontinuation 
from the study were considered related to ITI-007 in only 2.2% (31 of 1431) of the subjects. 
No deaths have occurred during the clinical studies. Nonfatal SAEs have been reported in 1.7% (25 of 1431) of 
subjects after administration of ITI-007. Only 1 SAE (single episode of convulsion) in a patient with 
schizophrenia was considered related to ITI-007, for an overall frequency of drug-related SAEs of 0.1%. The 
patient who experienced the convulsion had preexisting risk factors for seizures and was inappropriately 
randomized into the study (i.e., protocol violation) based upon an incomplete medical history and inaccurate 
self-reports of convulsions by the patient at screening. 
Overdose 


 
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Previous clinical trials have not evaluated ITI-007 at doses greater than a single dose of 40 mg or a multiple 
dose of 30 mg administered once daily for 7 days in healthy volunteers or greater than a multiple dose of 140 
mg in patients with schizophrenia. In case of an overdose that exceeds the previously studied doses, the 
patient should be closely monitored in a hospital setting with sufficient attention to the symptoms and the 
clinical course. Supportive measures may include gastric lavage and respiratory and cardiovascular support as 
needed. 
Drug Abuse and Dependency 
No formal studies have been conducted to assess the drug abuse or dependency potential of ITI-007 in 
humans. However, available data from clinical trials do not suggest that ITI-007 has the potential for drug 
abuse or dependency. Additionally, nonclinical data have indicated that neither ITI-007 nor ITI-131 (IC200131) 
produces tolerance or sensitization in male rats during repeated administration or a syndrome of behavioral 
and/or physical dependence on abrupt withdrawal (Study# RS1526). Neither ITI-007 nor ITI-131 (IC200131) 
was self-administered by rats, suggesting that ITI-007 and IC200131 are highly unlikely to be abused in a 
recreational manner by humans (Study# RS1545). 
Other Potentially Clinically Relevant Information   
Side effects in Canine studies:  
Toxicology studies of up to 6 months treatment duration have been conducted in rats and up to9 months in 
dogs. The available preclinical data for ITI-007 indicate that early symptoms are decreased activity in rats and 
decreased activity and changes in demeanor in dogs. These behavioral disturbances are reversible without 
intervention and wane with increasing time after administration of ITI-007, usually within 4 to 6 h. Adverse 
central nervous system histopathology that included axonal degeneration and perivascular cuffing occurred 
only in dogs after long-term repeated administration at high levels of exposure; these findings may not be 
relevant to humans given the striking differences in metabolism between dogs and humans. The major 
pathway of metabolism of ITI-007 in dogs in oxidation, whereas in humans it is direct glucuronidation and a 
combination of ketone reduction and glucuronidation. Nonclinical findings must be interpreted considering the 
quantitative differences in metabolism among species, particularly between dogs and humans. Nonetheless, in 
dogs, premonitory clinical signs of decreased activity, motor impairment, and tremor occurred early in 
administration and at lower doses than any adverse CNS histopathology; therefore, it is recommended that 
administration beyond 6 weeks treatment duration of ITI-007 be stopped upon signs of motor impairment or 
tremor. 
Rodent studies 
Based on neurohistopathology findings in the rodent (rats and mice) 104-Week Oral Gavage Carcinogenicity 
Studies with ITI-007 studies (see page 71-73 in the IB), the FDA has requested that the study be limited to six 
months and that study participants must receive an ophthalmologic exam (for retinal degeneration or 
pigmentation/deposits) at baseline and at the conclusion of the study (6 months). These neurohistopathology 
findings included sciatic nerve degeneration or edema, axonal degeneration in the spinal cord, infiltrates of 
pigmented macrophages (liver, lung, and brain), and retinal degeneration at doses (>10 mg/kg/day) more than 
double both the NOAEL level (5 mg/kg/day) and the equivalent human doses. None of these issues were 
noted in human studies. 
Genetics: ITI-007 showed potential to be toxic to genetic material (genes or DNA). When tested in two different 
animal studies, ITI-007 did not cause toxicity to genes and was well tolerated. Please see section 4.3.6 of the 
IB for full details. 
 


 
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Reproductive safety: Although a safety margin has been established in reproductive toxicity studies, at this 
time in the development process, ITI-007 should not be administered to pregnant and lactating females. 
Female subjects in this study must uses a highly effective methods of birth control:  
Methods of birth control considered to be effective include contraceptive implants, injectables, oral 
contraceptive pills, double barrier methods (condom with spermicide or a diaphragm with spermicide), some 
intrauterine devices (IUD), sexual abstinence, vasectomized partner. Subjects will be instructed to use a 
combination of at least two contraceptive methods with your partner during the study to ensure you do not 
become pregnant while taking the study medication and up to 3 months after the last dose of the study 
medication.  
 
The study medication may be passed in breast milk from mother to infant. Subjects will be instructed to not 
breast-feed while taking part in the study for at least 3 months post study. 
Male subjects with a partner that is of childbearing age must use contraception during 
the study and up to 3 months after the last dose of the study. 
 
CPK: In previous clinical studies with ITI-007 there have been instances of increased blood CPK levels. 
However, patients with increased blood CPK levels have been noted in all treatment groups, including placebo, 
during the screening period, study treatment period, and stabilization period. In most instances, these levels 
decreased while patients remained on study treatment. Patients were asymptomatic and, when tested, CPK 
elevations were associated with the skeletal muscle (CPK-MM) and not with the cardiac muscle (CPK-MB) 
isoform. Although these increases in CPK levels were notable, they are not uncommon in this patient 
population and do not appear associated with clinical signs and symptoms. Similar events have been 
described for other antipsychotic  medications. 
Dosing: Although administration with food is not necessary for safety, the frequency of adverse events 
decreased with administration of ITI-007 as a formulated capsule with food. Administering the formulated 
capsule with food lowers the maximal plasma concentrations of ITI-007 without changing the area under the 
curve, thereby maintaining overall exposure and improving tolerability. 
Methods to Protect Confidentiality 
Describe the data management plan and the methods you will employ to protect subject privacy and the confidentiality 
of research data.  The section should detail how information will be collected, recorded, coded, stored, transmitted, and 
as applicable, shared with other investigators so as to minimize risks related to breach of confidentiality.  Confirm that 
identifiers are removed, to the extent possible, from research data, and explain if there are links between subject identity 
and research data, or if the data is anonymous.  Also, indicate where the data is stored, who is responsible for its 
safekeeping, and who has access to subject identity and codes, if any, which cross-link research data and subject identity.  
Confirm that identifiable data is not collected, stored, or transmitted by mail, fax, on removable drives, laptops, or via the 
internet without proper protections, e.g. encryption. 
Describe methods to protect confidentiality 
Blood and urine samples, behavioral assessments, and all other 
clinical/neuropsychological data will be obtained from the subjects for specific research 
purposes. Data will include self-report information, observer records, and physiological and 
behavioral information collected during test sessions. Each subject is assigned a unique ID and all 
data related to that subject is entered at the site by the site data entry personnel.  
Study information will be collected at NYSPI, and entered into a secure electronic database stored at NYSPI. 
 


 
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Direct Benefits to Subjects 
Describe only benefits to individual subjects that are likely to accrue during the study itself. Do not include subject 
compensation or treatment to be provided at the end of the study, as these do not figure into the IRB's risk benefit 
considerations.  Do not describe diagnostic and evaluation components unless subjects receive clinical feedback. Do not 
describe the anticipated scientific benefits of the research.  Some studies offer no direct benefit to subjects. 
Participation in this study may or may not help with your symptoms. 
 
 


 
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References 
 
  See main protocol