Approved - Valid through 07-APR-2016

HIC#:1502015328

COMPOUND AUTHORIZATION AND CONSENT FOR PARTICIPATION IN A RESEARCH

PROJECT
200 FR. 4 (2014-4)
YALE UNIVERSITY SCHOOL OF MEDICINE YALE-NEW HAVEN HOSPITAL
Study Title: A Phase 1 Receptor Occupancy Study Using Positron Emission Tomography to Investigate Novel
Ligand [11C]TASP0410699 Alone and Following Single Oral Dose Administrations of TS-121 in Healthy Adult
(Male) Subjects
Principal Investigator:

Richard E. Carson, Ph.D.

Yale University School of Medicine
Yale University PET Center
P.O. Box 208042, LMP 89A
New Haven, CT 06520-8042
United States

Funding Source:

Taisho Pharmaceutical R&D Inc.

350 Mt. Kemble Avenue
Morristown, NJ 07960
Tel: 1-973-285-0870
Fax: 1-973-285-1665

CONSENT FOR PART 2 (Receptor Occupancy)

Invitation to Participate and Description of Project

You are invited to take part in a research study designed to evaluate a new radioactive compound (or
radiotracer) that has not yet been studied in humans, and the action of a new investigational drug, TS121, (a
drug that has not been approved by the FDA). The safety of the radiotracer and the investigational new drug
will also be monitored in this study.
Both the radiotracer and TS121 act on the pituitary gland, a small gland found at the base of the brain. The
pituitary gland releases chemical messengers (such as hormones) that combine with receptors to cause an effect
on the body. One such receptor, the vasopressin receptor 1b (V1b) found in the pituitary, plays a role in stress
and mood. TS-121 is an investigational new drug that attaches to the V1b receptor in the pituitary and prevents
other drugs or chemicals from binding, or being released, in the pituitary. It is being studied as a potential
treatment for Major Depressive Disorder (MDD).
The radiotracer [11C]TASP0410699 also attaches to the vasopressin receptor 1b (V1b) in the pituitary. In this
study, both the radiotracer and the study drug will compete to attach to the V1b receptor, and this will help to
determine how much of the study drug, TS-121, is needed to occupy the V1b receptor as much as possible so to
find the optimal dose for future use in persons with MDD.

Page 1 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

The study is separated into two parts and this consent form details the procedures for Part 2 (Receptor
Occupancy). In Part 2, we are studying healthy people. You have been asked to participate because you are in
good physical health, you are not addicted to drugs or alcohol, and you do not have any psychiatric illnesses.
We expect up to 15 subjects to complete this study (6 will complete Part 1, 9 will complete Part 2). There is a
60 day screening window for this study. Once you pass screening and are enrolled into the study, the total
duration of your participation in the study can be from 9 to 12 days.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. law.
This website will not include information that can identify you. At most, the website will include a summary of
the results. You can search this website at any time.
This study is not meant to provide treatment for a medical condition. In order to decide whether or not you wish
to be a part of this research study you should know enough about its risks and benefits to make an informed
decision. This consent form gives you detailed information about the study, which a member of the research
team will discuss with you. This discussion should go over all aspects of this research: its purpose, the
procedures that will be performed, any risks of the procedures, or possible benefits. Once all of your questions
about the study have been answered, you will be asked if you wish to participate; if so, you will be asked to sign
this form.
You will receive up to three injections of the radiotracer [11C]TASP0410699, and one dose of the study
drug TS-121 during Part 2 of the study.
We will be using an imaging technique called PET (Positron Emission Tomography). By agreeing to participate
in this research, you may be asked to undergo up to four PET scans. Three PET scans are planned, with a fourth
possible if necessary. You will only be asked to return for a fourth PET scan if there is a scan failure after
injection of the radiotracer. In that case, you may be asked to return to complete an additional radiotracer
injection to complete the study.
We will also use another imaging technique known as a Magnetic Resonance Imaging, or MRI. The MRI image
is important because it is often difficult to identify the brain structures and structures such as the pituitary in the
PET image, especially when they are small. The MRI creates a very detailed picture. By overlaying the PET
image onto the MRI image, we can measure the concentration of the receptors in the pituitary.
Please read the risks section below carefully concerning the potential risks of the study drug.
Description of Visits and Study Duration
If you agree to take part in this study, you will be asked to complete the following study visits:
Visit 1: Screening

The screening appointment will be completed at the Yale University PET Center and take approximately
2-4 hours to complete.

Visit 2: MRI Scan

The MRI session will take approximately 30 minutes and occur at the Magnetic Resonance Research
Center (MRRC). In the event that the MRI is able to be completed during the screening
Page 2 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

appointment at Visit 1, you would not need to return to complete the MRI on a different day prior
to admission.

Visit 3: Admission/Confinement

Admission/Check-in (Day -1) and Overnight Stay: The evening prior to your PET scans, you will
report to the Hospital Research Unit (HRU) for admission and an overnight stay. You may complete up
to 4 overnight stays at the HRU, depending upon the timing of study procedures.

Visit 4: Scan Period

PET scans (Day 1, Day 2, Day 3, or Day 4): You will be scheduled for three PET scans. A fourth
may be scheduled, if needed. All participants will complete PET scans. The experimental radioactive
compound (also called a radiotracer) used in this study is [11C]TASP0410699. At the beginning of each
PET scan, the tracer will be injected into your vein. A radiotracer is a low dose of a drug that has a
radioactive marker attached to it, so that it can be detected in the pituitary. The radiotracer gives off
energy (gamma-rays) that is detected by the PET scanner to create brain and pituitary images. For each
PET scan, we will take several pictures during a scanning session that will last up to 2 hours. Between
scans, you will be taken out of the PET scanner and allowed to rest. The radiotracer used in this study
will be almost completely gone from your body within 4 hours. You will be scheduled for no more than
2 PET scans per day. Upon completion of PET scans on Day 1, you will be escorted back to the clinical
unit for an overnight stay. You may complete an additional PET scan on the following day (Day 2). If
you are scheduled to complete PET scans on a subsequent day (on Day 3 or Day 4), you may need to
stay overnight until the last scan is completed (up to 4 overnight stays at most).

Drug Dosing A single oral dose (by mouth) of TS-121, of no more than 50mg, will be given on Day 1.
50 mg of TS-121 is the maximum dose that will be given in this study. Prior to drug dosing with TS121, and afterward, PET scans will be completed in order to determine how much TS-121 is attaching to
the V1b receptors in the pituitary. We call this measure receptor occupancy. One PET scan will be
performed before dosing, and up to two scans will be performed at appropriate times after dosing. The
pre-dose PET scan is referred to as the baseline scan, and will occur on Day 1. The scans that occur after
dosing may occur on Day 1, Day 2, Day 3, or Day 4.

Discharge You will be discharged after completion of the final post-dose PET scan, removal of the
arterial and venous catheters, and completion of all safety procedures. Discharge can occur between Day
2 (the day after TS-121 dosing) and Day 4, depending on how many PET scans are needed after TS-121
dosing.

NOTE: Scan days, times, and number of scans per day (1 or 2), may change. We will be in contact with you
well in advance regarding scheduling of your PET scans.
Visit 5: Follow-up

Follow-up Phone Call - You will be contacted by phone approximately 24-48 hours following completion
of your final PET scanning session for a follow-up assessment to assess how you are feeling. This will take
about 5 minutes of your time.

Follow-up Visit - You will have a follow-up visit approximately 7 days after dosing for a follow-up
assessment. At this visit, blood will be collected for clinical laboratory tests. It will also include a brief
Page 3 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

physical and neurological exam, ECG, measurement of vital signs, and assessment of any adverse events.
We will also ask you to report if you have taken any medications since discharge.

Description of Procedures
Screening
You will report to the Yale University PET Center at 801 Howard Ave, New Haven for your screening visit.
The purpose of this visit is to find out if you meet all of the requirements to take part in this research study.
You will be scheduled for a morning screening appointment and asked to fast (nothing to eat or drink
except water) for approximately 8 hours prior to arriving at the PET Center. The start time of your
fasting period will be confirmed by PET staff, based on the schedule of screening procedures.
During this visit, you will be asked whether you are interested in joining the study. If you agree to participate in
this study, you will complete a few brief questionnaires and complete a medical evaluation including the
following:

A review of your medical and psychiatric history including any electronic health records (EHRs)

Review of medications

Demography (age, race, ethnicity, etc.)

Physical examination, including measurements of height and weight

Vital signs (temperature, pulse, blood pressure, respiration rate)

Neurological examination

Electrocardiogram (ECG a test that measures the electrical activity of your heart)

Laboratory tests to ensure you are healthy and to measure several naturally occurring substances in
the blood and urine (e.g. levels of blood cells, sodium, potassium, chloride, carbon dioxide, liver
enzymes). In the event that your laboratory work cannot be completed prior to 9:00am on the day of
screening, you may be asked to return on a different day for collection of an additional blood sample
in order to test cortisol level in your blood.

Tests for hepatitis A, B, C, and HIV (positive HIV, hepatitis B, or C results will be reportable to the
Connecticut Department of Public Health)

Urine drug testing for illegal drugs of abuse and alcohol (you will not be allowed to participate in
this study if you test positive for illegal drugs or alcohol).

Measurement of urine cotinine levels (a biomarker of smoking)

During the physical examination, a small amount (about 3 tablespoons) of blood will be drawn from a vein in
your arm. This blood sample will be tested for hepatitis and HIV in addition to the other required blood tests
listed above for this study. Results of these tests are confidential. You will be notified if there are any clinically
important results. Positive hepatitis and HIV tests must be, by law, reported to the State Department of Public
Health and you will be given access to appropriate counseling and advice about the next steps to take. If any of
these tests are positive, you will not be able to participate in the study. If you do not want to risk this possibility,
you can refuse to have these tests done, but then you cannot participate in the study. You may be asked to return
Page 4 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

to complete additional blood tests and ECGs if your test results are out of range. All laboratory and ECG results
will be made available to you, if requested.
You will be asked a series of questions about potential psychiatric or medical symptoms that you may have
experienced during your lifetime. We will also ask if you have any family history of mental, emotional or drug
abuse problems. These questions help us determine whether you can participate in the study. All this will take
approximately 2-4 hours.
If you meet all requirements and decide to be in this study, you will also be visiting the Hospital Research Unit
(HRU). As part of your study procedures, some information about your participation in this research study will
become part of your HRU medical record. If you do not already have a medical record at the HRU, one will be
made for your visit. The information that will be entered into your medical record will include medical and
psychiatric history, physical exams, consent form, screening procedures, progress notes, nursing notes, and lab
investigations.
Re-Screening
In the event that your PET scanning session is postponed and is scheduled to occur more than 2 months (60
days) after your screening visit, you will be asked to return for an additional screening visit. This is to ensure
that you still meet all of the study criteria. This visit may include additional blood work, a physical exam and
possibly other assessments, depending on the study physicians judgment. You will be compensated $25-$50,
depending on the procedures completed.
MRI Scan
You will have an MRI (Magnetic Resonance Imaging) scan that will last about 20 minutes.

You may complete the MRI on the day of your screening appointment. In this case, you will be
escorted to the MRI Center by PET Center staff.

If the MRI is scheduled for a different day, you should report to the Magnetic Resonance Research
Center (MRRC) at The Anlyan Center (TAC) for Medical Research & Education, 300 Cedar Street,
in New Haven. You will be contacted to schedule your arrival time.

The MRI test involves lying inside the MRI scanner, which is a strong magnet. No metal can be on
your body or in your body. In the MRI Center you will be asked to fill out the Magnetic Resonance
Safety Check list, which will help to make sure that it is safe for you to have the MRI scan. The
technologist will escort you into the MRI room and ask you to lie on your back on the bed. When
you are comfortable, the bed will slide into the scanner and the test will begin. You will be asked to
lie still in the MRI scanner for about 20 minutes.

You will hear a drumming noise when the camera is taking pictures of your brain. If you feel
uncomfortable during the scan, we can end the scan at any time you wish to do so; however, if you
cannot complete the MRI scan, you will not be able to participate in any more of these studies.

Admission/Check-in and Overnight Stays at the Yale Center for Clinical Investigation (YCCI)/ Hospital
Research Unit (HRU)
If you are found to be eligible after the screening process by the Principal Investigator and/or study physicians,
you will visit the YCCI/HRU.
Page 5 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

You will be admitted to the HRU for a confinement period of one night prior to TS-121 dosing, and for up to
three additional nights after dosing.
We refer to the day of admission to the HRU as Day -1, the day of drug dosing as Day 1, and the day following
drug dosing as Day 2. You will be discharged from the clinical unit on either Day 2, Day 3, or Day 4, depending
on how many PET scans are needed (up to a maximum of 4 PET scans may be taken).
Confinement includes staying overnight in a private room on the hospital research unit. You will not be
permitted to leave the unit, except to complete study procedures at the PET Center. Strenuous activity, from 3
days prior to the admission visit and up until 48 hours after removal of the last arterial line, will not be
permitted.
Upon Admission at the HRU, the following procedures will be completed:

Your medical and psychiatric history and prior medications will be updated, if any changes have
occurred since the screening visit

A brief physical/neurological exam (including weight measurement)

Routine blood work, urine testing, and urine screening for the presence of illegal drugs, cotinine, and
alcohol (NOTE: if any of your labs are abnormal or your drug/alcohol/cotinine tests are positive,
your study participation may be cancelled). If the screening appointment has occurred within 48
hours of admission, certain tests may not need to be repeated, based on the study physicians
judgment.

ECGs

Vital signs measurements, including body temperature

Review of all inclusion/exclusion criteria to make sure you still qualify

For PET scanning, you will go to the PET Center. A PET staff member will meet you at the HRU and escort
you to the PET Center.
Drug Dosing
On Day 1 (dosing day), we will ask you to take the study drug (TS-121) by mouth with about one cup of water.
A nurse will check to make sure you have swallowed the drug. You will be required to fast for 6 hours prior to
receiving TS-121 and at least 4 hours after dosing. Your dose in this study will be no higher than the highest
dose shown to be safe and well tolerated in previous studies. You will be told, prior to dosing, what dose level
you will be asked to take. This dose will not be higher than 50 mg. Prior to taking the study drug, blood
samples, vital signs and ECGs will be obtained. An additional set of ECGs and vital signs will be acquired at
defined time points after dosing.
Blood samples will be drawn to measure the amount of drug in your blood; these samples are called PK
samples. These samples will be taken prior to dosing (a baseline sample, or sample with no drug in your
system), and at selected times after dosing.
After completion of the PET scan(s) you will be escorted to the HRU. You will be monitored overnight by
research staff. During the evening hours, your vital signs will be taken and blood will be collected. Research
staff will also be monitoring you for any adverse effects.
Page 6 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

PET Scan Session

You will participate in a PET scanning session at the Yale University Positron Emission Tomography (PET)
Center, 801 Howard Avenue, in New Haven.
Arrival Procedures
If admission procedures were not able to be completed at the HRU on Day -1, you will be asked to provide a
urine sample to test for illegal drugs of abuse, cotinine, and alcohol. If you have a positive result, your study
participation will be cancelled. You will also be asked how you are feeling and if you have taken any
medications.
Genetic Testing
You will also have a small sample of your blood (8.5mLs, less than 2 teaspoons) taken for future genetic
analysis. This is a required part of the study. Genes are the structures inside your cells that were passed to you
from your mother and father. In this study, we want to look at your blood to learn if your genes affect your
response to the PET radiotracer. The sponsor, Taisho Pharmaceutical R&D Inc., plans to keep your DNA
samples for up to 15 years following completion of data collection for this study. If the blood is not analyzed in
that timeframe, it will be destroyed. Your identity will be carefully guarded. We may study many different
genes in the course of this research. You may withdraw consent at any time. The results of any genetic analysis
conducted prior to consent withdrawal will be retained indefinitely by Taisho Pharmaceutical R&D Inc. In
general, individual results from the testing of the sample that you give us will not be made available to you.
This is because it will probably take a long time to fully understand the information we gain from these studies.
IV and Arterial Line
A trained nurse or CNMT (Certified Nuclear Medicine Technologist) will place plastic catheters (tubes) in your
arms (for the radiotracer injection, and to take venous blood samples, if necessary). An experienced physician
will insert an arterial catheter in your wrist area. A new arterial catheter will be inserted on each PET scan day.
The arterial catheter is about 2 inches long, looks like a regular IV tube, but is inserted into an artery, not a vein.
The blood flow in the arteries can tell us about your blood pressure. If an arterial catheter is in place, we can
measure your blood pressure continuously. The other main reason to put in an arterial catheter is to be able to
draw blood samples rapidly, repeatedly, and without causing you pain.
Here is what happens when an arterial line is placed. First, the skin is cleaned with betadine solution (contains
iodine). This skin cleansing with an antiseptic aims to reduce the germs or bacteria present on the skin and
therefore reduces the risk of an infection. Second, the insertion area is numbed with a local anesthetic, so that
you feel less pain when the catheter is inserted. You will probably just feel pressure but may also feel pain. This
pain is usually like the pain you feel when an IV is placed and only rarely is it worse. Third, the catheter will be
flushed regularly during your scan with saline (a salt solution), which prevents clogging of the catheter with a
blood clot. You should not feel any discomfort when this is done. Fourth, after the catheter is removed, local
pressure is applied for a minimum of 15 minutes to prevent bleeding under the skin. A pressure dressing
(coban) and clear dressing (tegaderm) will then be applied and you will be asked to keep it clean and dry, avoid
strenuous exercise, refrain from lifting heavy objects weighing more than 5 pounds, and to avoid repetitive
movements for 48 hours. You may remove the pressure dressing at bedtime and the clear dressing after 48
hours, but do not submerge your hand and wrist in water for a full 72 hours. Since the catheter is in for a
minimal period, there is a low risk of infection.

Page 7 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

Radiotracer Injection and PET Scan

After the arterial catheter is inserted, you will receive the radiotracer [11C]TASP0410699 (a drug which is
limited by Federal Law for investigational use only) during the PET scan. This radiotracer, which is a minimal
amount of a drug that is labeled with a very small amount of a radioactive substance, binds to receptors in the
pituitary and can be detected by a special camera in the PET scanner. As part of the PET scanning session, you
will be asked to lie very still on a table. The radiotracer will then be injected into the tube in your vein.
Following the injection, the PET scanner camera will detect the radiotracer present in the pituitary. This
information will be used to create pictures of your pituitary. Blood samples during the PET scanning sessions
will be used to measure the amount of radiotracer in your blood. Samples will be stored at the PET Center until
analysis. The analysis of the samples will take place at Yale University laboratories. You will be asked to drink
several glasses of water at the close of the PET scanning session to wash out the radiotracer. After the PET
scanning session you will be examined by a study physician at the PET Center. You will be provided with a
telephone number you can call anytime after the study if you need assistance for problems related to the study
procedures.
The following will also occur during the PET scanning session:

Your vital signs will be taken throughout your PET scan days.

In the unusual circumstance where there are some technical problems with the scanning equipment,
if appropriate, the timing of one of your scans may be adjusted. You may also be asked to return on
another day, and complete an additional arterial line placement.

If you ask to stop any aspect of your participation in the study, including the scan(s), we can stop at
any time.

A brief physical and neurological exam will be completed prior to discharge from the PET Center.

A light meal will be provided at the end of the PET scanning day(s). Meals will also be provided
during your confinement period at the clinical unit.

After completion of the baseline scan, at the appropriate time, we will ask you to take the study drug
(TS-121) by mouth. Your dose in this study will be no higher than 50 mg, the highest dose tested in
the previous healthy human subject study.

After completion of scanning on Day 1, your arterial and venous lines will be removed and you will
be escorted back to the HRU for an overnight stay.

When you are escorted back to the PET Center on Day 2, Day 3, or Day 4, the venous and arterial
catheters will be placed again as described above.

You will be discharged from the clinical unit on Day 2, Day 3, or Day 4, after completion of all PET
scanning, a brief physical, neurological exam, ECG, measurement of vital signs, and collection of
blood for laboratory tests.

Acting as a Back-Up
You may be asked to act as a back-up subject. This means you have already been screened to participate in the
study, but have not yet been scheduled for a study session. It would mean being on-call in the event of a last
minute cancellation. This may involve completion of admission procedures (physical, ECG, and vital signs) at
the HRU or Yale University PET Center, in order to check that you meet all study requirements. You would
then stay on site until the scheduled participant has begun the study. You would be paid for your time. If the
Page 8 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

scheduled participant cancels or is unable to continue, you would then complete the study that day(s), and be
paid for the study procedures as listed below.
Cancellations
In the event that your PET scan day gets cancelled for reasons outside of your control (such as radiotracer
synthesis failure), you will receive a minimum payment of $50 per cancelled scan, or a higher amount not to
exceed the amount for a full scan day. This amount will be based on your length of participation on the scan day
prior to cancellation, and will be up to the discretion of the PI.
RESTRICTIONS/ YOUR RESPONSIBILITIES
You will be called by a staff member prior to admission to be reminded of the restrictions listed below.

You will be provided with a telephone number you can call any time after the study if you need
assistance for problems related to the study procedures.

Because the radiotracer [11C]TASP0410699 is in the early stage of investigation, the potential for
interactions with other drugs is not presently known.

Please tell your doctor if you have taken part in other research studies at Yale or other places/hospitals
that used radiation. This way, we can make sure that you will not receive too much radiation. You
should consider x-rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well
as nuclear medicine scans, in which radioactive materials were injected into your body. Before you take
part in any future studies that use radiation, you should also tell those study doctors about your
participation in this study. You are encouraged to inform your family doctor and your other healthcare
providers that you are taking part in this research study.

You will be asked to fast (nothing to eat or drink except water) for 8 hours prior to collecting routine
blood work on the screening day.

You will check into the HRU on the day prior to scanning, referred to as Day -1, and may be discharged
from the PET Center upon completion of study procedures on Day 2, Day 3, or Day 4.

You will be required to fast (no food) for at least 6 hours prior to receiving TS-121 and for 4 hours after
(if a scan is delayed for some reason, a light snack may be provided).

Strenuous activity is prohibited for at least 3 day(s) prior to admission, and for up to 48 hours after
removal of the final arterial catheter. After this time, mild physical activity can be resumed, but
strenuous physical activity is prohibited until completion of the final follow-up phone call.

You will be asked to abstain from all caffeine-containing products for 24 hours prior to study admission
through study discharge.

You will be asked to abstain from alcoholic beverages for 24 hours prior to study admission and
throughout the duration of the confinement period.

You will be asked to drink 2 to 3 glasses of water the night prior to and after your PET scan(s).

You will be asked to refrain from donating blood for at least 8 weeks after the study completion.

You must not use any prescribed or non prescribed drugs (including vitamins, mineral supplements,
hormone-containing medications, or natural and herbal remedies, such as St. Johns Wort) within 2
weeks of admission, except for occasional use of acetaminophen (Tylenol) and non-steroidal topical
agents.
Page 9 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

You will be asked to reschedule your study participation visits should you acquire a cold, upper
respiratory tract infection, or fever, within 5 days prior to admission.

Men in this research study should not get a sexual partner pregnant while participating in the study and
for 90 days after completing the study and must agree to use 2 forms of highly effective method of birth
control with their partner of childbearing potential during this time. In addition to condom use,
acceptable methods of birth control for men include vasectomy and abstinence. Female partners should
have one of the following: use of hormonal birth control (birth control pills, injectable progesterone,
subdermal implant), IUD placed, or use of spermicidal foam. This list is not exhaustive. The research
staff will inquire if other medical conditions regarding you or your partner are applicable (such as
whether your partner has been through menopause or had her ovaries removed). Any single method of
birth control, including vasectomy and tubal ligation, may fail, leading to pregnancy. Males must refrain
from sperm donation during the study and for 90 days following the last study drug dose. The effect of
the study drug on sperm is not known. If a partner becomes pregnant during the study or within 90 days
after the study, the Principal Investigator should be notified immediately. Information about pregnancy
and outcome will be collected.

Risks and Inconveniences

There may be side effects related to your participation in this study (or to the unborn baby if your partner
becomes pregnant) that are not known at this time. Your health and safety will always be the first concern of the
doctors and staff performing this study. You may be withdrawn from this study at any time if the Principal
Investigator or study physician feels it is in your best interest to do so.
You will be told of any significant new findings that are developed during the course of your participation in
this study that may affect your willingness to continue to participate.
Possible risks from participation in this study include:

Risks associated with evaluation

Risks associated with use of an arterial line

Risks associated with radiation

Risks associated with the study drug, TS-121

Risks associated with blood drawing and IV line insertion

Risks associated with MRI scanning

Risks associated with any medication

Risks associated with genetic testing

Risks Associated with Evaluation

Some of the questions in the interviews may be painful or uncomfortable for you to answer. You may refuse to
answer any specific questions or discontinue the interview at any time. The tasks and structured interviews may
be tiring, but every effort will be made to avoid making you tired. Breaks will be offered frequently and you can
quit at any time if you get tired. However, if you cant complete the evaluation process, you may be disqualified
from the current study. During the evaluation we might uncover unanticipated psychiatric and medical
information. In that case we will discuss with you the findings and will advise you of appropriate follow-up.
Page 10 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

Risks Associated with Use of an Arterial Line

Important: If you have a history of a bleeding disorder or are taking medication to thin your blood, you will not be
allowed to participate in this study.
Putting in the plastic tube into the artery in the wrist area may cause bruising, and potentially infection. The
arterial puncture may also cause spasm or clotting of the artery with a temporary decrease in blood flow,
hematoma (swelling of blood within the tissues), bleeding, or inflammation. If this occurs, signs and symptoms
will dissipate over time, usually 24 to 72 hours after the event. In rare instances, blocking of the artery, poor
healing, or infection at the catheter insertion site may occur. Insertion of arterial catheters for sampling blood
may be associated with mild-to-moderate pain or bruising at the puncture site. To minimize these risks, an
experienced physician will insert the arterial line and a trained nurse will oversee subject care.
For two days following the placement of the arterial line, you should check your wrist/arm daily. If you
experience any excessive pain, tenderness, swelling, redness, drainage, skin color changes, numbness, pins
and needles, or decreased strength in the arm that had the catheter, you should immediately call your
study team or the PET Center Physicians Dr. David Matuskey at 203-370-1403 (pg) or Dr. Ming-Kai
Chen 203-766-4241 (pg) (You will need to punch in your telephone number with area code followed by
the, #, sign).
You may experience a rare allergic reaction to the medicine used to numb your skin prior to placement of the
arterial catheter. If you have had a bad reaction to lidocaine, Novocain, or other anesthetic agents used to numb
the skin in the past, please tell us about this experience before you go through the arterial line placement. Severe
allergic reactions can be life threatening. You will be also asked to abstain from using aspirin or NSAIDS,
which can thin the blood, for 14 days prior to arterial line insertion and for 7-10 days following arterial line
removal.
Risks Associated with Radiation
This research study involves exposure to radiation from positron emission tomography (PET). Please note that
this radiation exposure is not necessary, and is for research purposes only.
The targeted amount of radiation you will receive from participating in this study is from 3 injections of
[11C]TASP0410699 plus transmission scans (used to help obtain the PET images). However, in situations where a
PET scan is not successful following a [11C]TASP0410699 injection (e.g. problems with the PET camera), you
may receive an additional [11C]TASP0410699 injection, for up to a total of 4 injections of [11C]TASP0410699
during the study.
Although each organ in your body will receive a different dose of radiation, the targeted amount of radiation
exposure you will receive from this study is from 3 injections of up to 20mCi each of [11C]TASP0410699. This
is equal to a uniform whole-body exposure of 1.11 rem, which is the equivalent of approximately 3.7 years of
natural environmental exposure from sources such as naturally occurring radioactive forms of water and
minerals. The maximum amount of radiation exposure you will receive from this study is from up to 4
injections of [11C]TASP0410699. This is equal to a uniform whole-body exposure of 1.48 rem, which is the
equivalent of approximately 5 years of natural environmental exposure. This exposure value is known as the
effective dose equivalent and is used to relate the dose received by each organ to a single value. This amount
of radiation exposure is below the annual limit of 5 rem set by the federal government for research subjects.

Page 11 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

The effects of radiation exposure on humans have been studied for over 60 years. In fact, these studies are the
most extensive ever done of any potentially harmful agent that could affect humans. In all these studies, no
harmful effect to humans has been observed from the levels of radiation you will receive by taking part in this
research study. However, scientists disagree on whether radiation doses at these levels are harmful. Even though
no effects have been observed, some scientists believe that radiation can be harmful and may cause cancer at
any dose- even low doses such as those received during this research.
Please tell your study doctor or other study personnel if you have taken part in other research studies at Yale or
other places/hospitals that used radiation. This way we can make sure that you will not receive too much
radiation. You should consider x-rays taken in radiology departments, cardiac catheterization, and fluoroscopy
as well as nuclear medicine scans in which radioactive materials were injected into your body. Before you take
part in any future studies that use radiation, you should also tell those study doctors about your participation in
this study.
Risks Associated with the Study Drug, TS-121
TS-121 is being developed for the treatment of Major Depressive Disorder (MDD). This study is being done to
learn about the interaction of the study drug and V1b receptors in the pituitary. We want to understand how
these receptors are affected by the study drug. For example, we will be able to learn more about possible side
effects of the study drug. For this reason and for your own safety, it is important that you tell the research staff
of any changes in your general health or of any symptoms that you may notice, even if you think that these
changes or symptoms are not related to the study drug.
All drugs carry a risk of side effects. Ask the research staff if you have any questions about the signs or
symptoms of side effects listed in this consent form. During this study, you may experience none or some of the
side effects listed below. You will be monitored for the occurrence of possible side effects.
Single doses of TS-121 or placebo have been tested in up to 51 subjects. Subjects have been administered TS121 or placebo in single doses ranging from 0.5mg through 50mg. There have been no safety or tolerability
concerns with doses of TS-121 up to and including 50mg.
Adverse events (AEs) reviewed to date have been blinded. This means it is not known if the subject received
TS-121 or placebo. Of the subjects dosed between 0.5-50 mg, the following AEs were documented:

0.5mg: Increased Warmth (at night)

2.5mg: Venipuncture Site Bruise (unrelated to study drug), Dry Mouth, Sore Throat, Headache,
Feeling of Relaxation, Heart Palpitations, Heart Rhythm Disturbance, Abdominal Cramping, Cold
Symptoms

4mg: Venipuncture Site Bruise (unrelated to study drug), Drowsiness, Shortness of Breath, Fatigue,
Depression, Dizziness

8mg: Pain/Bruising at Venipuncture Site (unrelated to study drug), Loose Stool, Musculoskeletal
Chest Pain

15mg: Blister to Upper Lip Mucosa, Skin Irritation at ECG Pad Site (unrelated to study drug),
Dizziness, Low Back Pain (unrelated to study drug), Hot Sensation, Vasovagal Symptoms (Feeling
Faint), Headache
Page 12 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

30 mg: No adverse events were reported at the 30 mg dose level

50 mg: Eye Irritation (unrelated to study drug), Blood in Stool (single time), Muscle Spasm
(unrelated to study drug)

No severe or serious side effects were reported at any of the dose levels studied.

Risks Associated with Blood Drawing and IV Line Insertion

Drawing blood and inserting an intravenous line (IV) into an arm vein are safe and standard medical
procedures. Sometimes a bruise will occur at the puncture site and rarely a blood clot or infection will occur in
the vein. You should not donate blood for at least 8 weeks after the study. The total volume of blood collected
during this study will be up to 32 tablespoons, including screening laboratories, blood drawn from your vein
and/or artery during the your PET scan day(s), blood drawn for genetic testing, and safety laboratories at
admission, discharge, and follow-up. This amount of blood is safe for healthy persons.
Risk Associated with MRI Scanning
Magnetic resonance imaging (MRI) is a technique that uses magnetism and radio waves, not x-rays, to take
pictures and measure chemicals of various parts of the body. The United States Food and Drug Administration
(FDA) has set guidelines for magnet strength and exposure to radio waves, and we carefully observe those
guidelines.
You will be watched closely throughout the MRI study. Some people may feel uncomfortable or anxious. If
this happens to you, you may ask to stop the study at any time and we will take you out of the MRI scanner. On
rare occasions, some people might feel dizzy, get an upset stomach, have a metallic taste or feel tingling
sensations or muscle twitches. These sensations usually go away quickly but please tell the research staff if you
have any of these symptoms.
There are some risks with an MRI study for certain people. If you have a pacemaker or some metal objects
inside your body, you may not be in this study because the strong magnets in the MRI scanner might harm you.
Another risk is the possibility of metal objects being pulled into the magnet and hitting you. To reduce this risk
we require that all people involved with the study remove all metal from their clothing and all metal objects
from their pockets. We also ask all people involved with the study to walk through a detector designed to detect
metal objects. It is important to know that no metal can be brought into the magnet room at any time. Also,
once you are in the magnet, the door to the room will be closed so that no one from outside accidentally goes
near the magnet.
We want you to read and answer very carefully the questions on the MRI Safety Questionnaire related to your
personal safety. Take a moment now to be sure that you have read the MRI Safety Questionnaire and be sure to
tell us any information about you that you think might be important.
This MRI study is for research purposes only and is not in any way a clinical examination. The scans
performed in this study are not designed to find abnormalities. The Principal Investigator, the lab, the MRI
technologist, and the Magnetic Resonance Research Center are not qualified to interpret the MRI scans and are
not responsible for providing a diagnostic evaluation of the images. If a worrisome finding is seen on your
scan, a radiologist will be asked to review the relevant images. Based on his or her recommendation (if any),
the Principal Investigator or consulting physician will contact you, inform you of the finding regarding you, and
recommend that you seek medical advice as a precautionary measure. The decision for additional examination
Page 13 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

or treatment would lie solely with you and your physician. The Principal Investigator, the consulting physician,
the Magnetic Resonance Research Center, the Sponsor and Yale University are not responsible for any
examination or treatment that you receive based on these findings. The images collected in this study are not a
clinical MRI exam and for that reason, they will not be made available for diagnostic purposes.
Risks associated with any medication
Any medication may cause allergic reactions. If you have a very bad allergic reaction, it could be lifethreatening. Some things that happen during an allergic reaction are:

Rash

Hives

Having a hard time breathing

Wheezing when you breathe

Sudden drop in blood pressure

Swelling around the face, mouth, lips, tongue, throat, or eyes

Fast pulse

Sweating

If you have any of the above side effects or symptoms, report to your study doctor immediately.
You are strongly encouraged to inform your family doctor and your other healthcare providers that you are
taking part in this research study. The study doctor may ask you to stop taking certain drugs that could interfere
with the study. The study doctor will explain any risks involved with stopping those drugs. You should always
notify the study doctor before starting any new drugs (prescription or over the counter) during the course of the
study, to ensure there is no risk in taking the drugs at the same time as receiving the study drug.
If you experience any side effects or unusual events during the course of the study, report them immediately to
the study doctor or research staff. If, in the opinion of the study doctor, there are any problems possibly caused
by the study drug that makes it unwise for you to continue, you will be withdrawn from the study.
Risks Associated with Genetic Testing
Sometimes, it can be a risk for genetic information about you to be known as it can lead to discrimation by insurance
companies or employers. We will keep all results confidential as noted below.

To guard the confidentiality of genetic material, we will do the following:

1) The genetic testing of your DNA is for research purposes only. No results of genetic testing from this study
will appear in your medical record.
2) Genetic test results will not be made available to you, your doctors, your other clinicians or any other clinical
staff.
3) When your specimen and information are stored, we are careful to try to protect your identity from discovery
by others. Your sample and information will receive a unique code. Other researchers will only receive a
Page 14 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

coded sample and information, and will not be able to link the code to you. Strict security safeguards are in
place to reduce the chance of misuse or unplanned release of information.
4) Your genetic sample will be stored at a lab designated by the sponsor (Taisho) for up to 15 years. These
samples will be coded.
Please note that the DNA sample will be coded so that it does not contain any identifiers and, therefore. will
have absolutely no link to your personal identity. There is a federal law called the Genetic Information
Nondiscrimination Act (GINA) that, in general, makes it illegal for health insurance companies, group health
plans, and most employers(except those with fewer than 15 employees) to discriminate against you based on
your genetic information. However, it does not protect you against discrimination by companies that sell life
insurance, disability insurance, or long-term care insurance.
While all efforts are aimed at protecting and guarding your DNA sample, there remains the possibility that Yale
University could be compelled by a court or a law enforcement agency to produce such samples. In more than
sixteen years of collecting DNA samples here at the Yale University, in which many thousands of samples have been
collected, no outside agency has ever tried to gain access to any research participant's DNA samples. We believe that
the risk of this happening to your sample is small. The records of potential subjects who did not enroll in the study or
subjects who withdrew from the study will be retained in the same manner as described above.

Benefits
There is no direct medical benefit to you from participating in this study, except you may gain information
about your health from the different tests that are done. It might also lead to treatments that help others in the
future. Society may benefit from these insights, as this research information may have clinical application in the
future.
Economic Considerations
For your participation in Part 2 of this study, you will be paid:
Study Days
Payment
Screening Session
$75
MRI Session
$100
Repeat Screening Blood Work and/or $25
ECG (if needed)
Arterial Line
$50 (per arterial line
insertion)
PET Scans
$400 (per PET scan)
Administration of Study Drug
$200
Overnight Stay
$250 per overnight stay
Follow-up Visit
$25
Back-Up Subject
$75 (per day)

Payment Method
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card
Check or BOA pre-paid debit card

You will receive an additional compensation of $400 by check when all procedures, including the
follow-up phone call and the follow-up visit, are completed.
Page 15 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

The total amount that you are expected to be compensated will be up to $2600, if all study procedures
are completed. This includes completion of screening, MRI, 2 arterial lines, 3 PET scans, drug dosing,
2 overnight stays, and a follow-up visit. The total would be increased if additional overnight stays or
any other procedures are completed. Additional procedures may include another arterial line
placement and PET Scan (in the event of scan failure after radiotracer injection), or additional
screening blood work and/or ECG. Additional overnight stays may be needed in the event of
rescheduling due to cancellation. You will be paid the same rate for additional procedures and
overnight stays as listed in the table above.

All study procedures will be provided free of charge.

Parking will be validated and reasonable transportation costs will be reimbursed. Receipts must be
submitted. You will be required to contact the study coordinator prior to your study date to discuss
transportation plans and confirm that they will be appropriate for reimbursement.

There will be no additional costs to you for your participation in this study.
You will receive compensation only after you have completed as many parts of the study as you can.
Method of Payment
For this study you may be paid by check or Bank of America (BOA) pre-paid debit card. All transportation
reimbursements will be paid by check. Please allow 4-6 weeks for receipt of your check. Study procedures may
be paid by check or a BOA pre-paid debit card.
If you are paid via a BOA card, please note that your name, address, and telephone number will be shared
with Bank of America. Upon completion of the study, you will receive a card in the mail which you will need
to activate over the phone. Any subsequent payments, if remaining, will automatically add additional funds to
your card.
Please follow these instructions to activate your BOA pre-paid debit Card:
To activate your card over the phone, if you are calling from the number registered to the card, you will be
prompted to enter the card number and the CVV2 (security code on the back of the card).
If you are calling from a different number, you will have to enter the card number and the last 4 digits of the
phone number registered to the card. If there was no phone number registered to the card then then the phone
number will be set up as 999-999-9999.
If you are unsure of what phone number was registered please contact your study coordinator. If you activate
via the website, you will be asked for the card number and the last 4 digits of the phone number.
You will be prompted to set a pin number after successfully activating their card with either method.
Card expiration defaults to 3 years with an automatic renewal option. The card may be used for multiple Yale
research studies, if they use the BOA payment method.
Treatment Alternatives/Alternatives
This is not a treatment study. Your alternative is not to participate in this study.

Page 16 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

Confidentiality and Privacy

Any identifiable information that is obtained in connection with this study will remain confidential and will be
disclosed only with your permission or as permitted by U.S. or State law. Examples of information that we are
legally required to disclose include abuse of a child or elderly person, or certain reportable diseases. All data is
securely stored in locked filing cabinets or on a password-protected computer server. When the results of the
research are published or discussed in conferences, no information will be included that would reveal your
identity unless your specific consent for this activity is obtained.
As a participant in a clinical research study involving the Yale-New Haven Hospital (YNHH) Research Unit
(HRU), it is important for you to know that if you do not already have a medical record at YNHH, one will be
made for your admission. In addition, you need to know that if you have ever been a patient at YNHH at any
time, your previous medical records of other visits or admissions will become available to the researchers and to
the staff of the HRU when todays information is added into the medical record.
We understand that information about you obtained in connection with your health is personal, and we are
committed to protecting the privacy of that information. If you decide to be in this study, the researcher will get
information that identifies you and your personal health information. This may include information that might
directly identify you, such as your name and date of birth. This information will be de-identified at the earliest
reasonable time after we receive it, meaning we will replace your identifying information with a code that does
not directly identify you.
For the purposes of your participation in this study and the protection of your identity, your study doctor will
assign you a unique code, such as a series of numbers and/or letters. The study doctor will record the study data
collected from you in a report form that uses your assigned code, not your name. This is to protect your study
data by making it anonymous for most study purposes.
The data that is recorded with your assigned code rather than your name is called key-coded data. The keycoded data will be entered into the studys computer database. Your study doctor will keep a confidential list
linking your name to your code and only authorized persons will have access to this list.
The Principal Investigator will keep a link that identifies you to your coded information, and this link will be
kept secure and available only to the PI or selected members of the research team. Any information that can
identify you will remain confidential. Information about your participation in this study is stored in locked file
cabinets. The research team will only give this coded information to others to carry out this research study. Deidentified PET data will be kept for a minimum of 7 years.
The information about your health that will be collected in this study includes:

Research study records

Medical and laboratory records for those services provided in connection with this Study.

Medical and laboratory records stored in EPIC for previous standard of care or research visits

The entire research record and any medical records held by Yale-New Haven Hospital created from
study enrollment to study discharge
Records about phone calls made as part of this research
Records about your study visits
Page 17 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

Information obtained during this research regarding:

HIV/Hepatitis
Physical Exams
Laboratory Results
Questionnaires
Records about any study drug you received
Data from PET scans
Information about you and your health which might identify you may be used by or given to:

The U.S. Department of Health and Human Services (DHHS) agencies Representatives from Yale
University and the Human Investigation Committee (the committee that reviews, approves, and monitors
research on human subjects), who are responsible for ensuring research compliance. These individuals
are required to keep all information confidential.

The Yale-New Haven Hospital Radiation Safety Committee.

Those individuals at Yale who are responsible for the financial oversight of research including billings
and payments.

The U.S. Food and Drug Administration (FDA). This is done so that the FDA can review information
about the new drug product involved in this research. The information may also be used to meet the
reporting requirements of drug regulatory agencies (including international agencies).

Health care providers who provide services to you in connection with this study.

Laboratories and other individuals and organizations that analyze your health information in
connection with this study, according to the study plan.

The study sponsor, Taisho Pharmaceutical R&D Inc., including sponsor representatives who are
checking that the study is conducted properly.

The Principal Investigator, Richard E. Carson, PhD.

Co-Investigators.

Study Coordinator and Members of the Research Team.

By signing this form, you authorize the use and/or disclosure of the information described above for this
research study. The purpose for the uses and disclosures you are authorizing is to ensure that the information
relating to this research is available to all parties who may need it for research purposes including any future
review.
All health care providers subject to HIPAA (Health Insurance Portability and Accountability Act) are
required to protect the privacy of your information. The research staffs at the Yale School of Medicine and
Yale New Haven Hospital are required to comply with HIPAA and to ensure the confidentiality of your
information. Some of the individuals or agencies listed above may not be subject to HIPAA and, therefore,
may not be required to provide the same type of confidentiality protection. They could use or disclose your
information in ways not mentioned in this form. However, to better protect your health information,
Page 18 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

agreements are in place with these individuals and/or companies that require that they keep your information
confidential.
The sponsor will see the research information we collect about you when they come to Yale to monitor the
conduct of this research study. The sponsor may also observe study procedures to ensure they are being
conducted as listed in the protocol. The sponsor includes any persons that work for or are hired by the sponsor
to conduct research activities related to this study. For this study, the sponsor is Taisho Pharmaceutical R&D
Inc. Yale researchers will also send the sponsor your health information during the study or at the end of the
study. When Yale researchers send information about you to the sponsor, they will not send information that
directly identifies you such as your name or address. The sponsor may also use the information about you for
other purposes related to this research or to similar research studies.
The study sponsor, Taisho Pharmaceutical R&D Inc., and the investigational center, Yale, will process your
personal data, in particular those associated to your health and, only if they are relevant to the objectives of
this study, those associated to your ethnic origin, lifestyles, sexual life, only to conduct this research and for
pharmacovigilance purposes. In this regard, your personal data will be sent to the third parties designated by
the sponsor to conduct the data processing and then sent to sponsor. By signing this form, you authorize the
data process and transfer of data as described above.
Information from this study will be collected in a computer database that is accessed remotely from the study
site. Study related information is entered into this database using the sites own computer and is transmitted by
way of a secured internet connection. This computer database meets all regulatory requirements for use in
clinical studies and access is restricted to trained study personnel.
You have the right to review and copy your health information in your medical record in accordance with
institutional medical records policies. However, by deciding to take part in this study and signing this
permission form, you will not be allowed to look at or copy your study related health information until after the
research is completed.
This authorization to use and disclose your health information collected during your participation in this study
will never expire.
If you revoke this authorization, you will not be able to stay in the study. If you drop out of the study, you do
not have to revoke this authorization. If you drop out and decide to revoke your authorization, the information
and study samples (whether analyzed or not) that have already been collected may continue to be used and
disclosed as described above. If you cancel this authorization, your personal health information under the
authorization for this study will no longer be used or disclosed, unless the study doctor needs to use or disclose
some of your personal health information to preserve the scientific integrity of the study. Information given to
the sponsor before you cancel this authorization may still be used by the sponsor. No new information will be
added.
Information about your study participation will be entered into your Electronic Medical Record (EMR). Once
placed in your EMR, these results are accessible to all of your providers who participate in the EMR system.
Information within your EMR may also be shared with others who are appropriate to have access to your EMR
(e.g. health insurance company, disability provider.)

Page 19 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

In Case of Injury
If you believe you have been injured, please contact the Study Physician, Dr. David Matuskey, at (203) 3701403 (pager), office: (203) 737-6316, or Principal Investigator, Dr. Richard E. Carson, at (203) 737-2814, as
soon as you are able.
If you seek emergency care, or if hospitalization is required, please inform the treating doctor that you are
participating in a clinical trial.
Medical care will be provided for any physical injury or illness that occurs as a direct result of your
participation in this study. Medical care will be arranged through Yale-New Haven Hospital.
If you become ill or are physically injured due to the study drug or any investigational procedure specifically
required by the plan for this study, you will not be responsible for the costs required to diagnose or treat such an
injury.
The sponsor will pay for all reasonable and necessary medical expenses incurred if you are enrolled in the study
and suffer a direct injury as a result of the following:
a) Taking the study drug administered according to the directions listed in this consent form
b) Research procedures required and conducted in accordance with this consent form
c) The injury is not caused by the Institutions, Principal Investigators or associated staffs negligence or
willful misconduct
If you receive a bill for any costs related to the diagnosis or treatment of your injury, please contact the study
doctor.
A study-related injury does not include injuries directly caused by the following:

Not following the instructions provided in this consent form or by study staff

There are no plans to provide any other payments or other forms of compensation for a study-related injury (for
example, for lost wages or discomfort). However, by agreeing to participate in this research study, you are not
waiving or giving up any legal rights to seek compensation.
Voluntary Participation and Withdrawal
Participating in this study is voluntary. You are free to choose not to take part in this study. Refusing to
participate will involve no penalty or loss of benefits to which you are otherwise entitled (such as your health
care outside the study, the payment for your health care, and your health care benefits). However, you will not
be able to enroll in this research study and will not receive study procedures as a study participant if you do not
allow use of your information as part of this study.
Withdrawing From the Study
If you do become a subject, you are free to stop and withdraw from this study at any time during its course. If
you sign this authorization, you may change your mind at any time, but the researchers may continue to use
information collected before you changed your mind to complete the research. We cannot discard or destroy
Page 20 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

data once it is collected. However, you can be assured that if you withdraw from the study, the information
collected will be coded in such a manner that it cannot be traced back to you.
To withdraw from the study, you can call a member of the research team at any time and tell them that you no
longer want to take part. This will cancel any future appointments
The researchers (Principal Investigator and/or study physician) may withdraw you from participating in the
research if necessary. Conditions under which a subject might be withdrawn from the research include
development of serious side effects, or if the subject does not follow the instructions given to them by the
investigator.
Withdrawing from the study will involve no penalty or loss of benefits to which you are otherwise entitled. If
you choose not to participate, or if you withdraw on your own, it will not harm your relationship with your own
doctors or with Yale-New Haven Hospital.
Please note that if you withdraw from the study early, we still ask that you agree to complete discharge procedures,
in order to ensure your safety. A study team member will still follow-up with you by phone within 24-48 hours after
your study withdrawal to inquire about any adverse events. You may also be asked to return to the PET Center in
order to complete follow-up procedures, as a final safety assessment. This does not apply if you withdraw after only
completing the screening appointment.

Withdrawing Your Authorization to Use and Disclose Your Health Information

You may withdraw or take away your permission to use and disclose your health information at any time. You
may withdraw your permission by telling the study staff or by writing to the Principal Investigator:
Richard E. Carson, Ph.D.
Yale University School of Medicine
Yale University PET Center
P.O. Box 208042, LMP 89A
New Haven, CT 06520-8042
United States
If you withdraw your permission, you will not be able to stay in this study.
When you withdraw your permission, no new health information identifying you will be gathered after that
date. Information that has already been gathered may still be used and given to others until the end of the
research study, as necessary to insure the integrity of the study and/or study oversight.

Questions
We have used some technical terms in this form. Please feel free to ask about anything you don't understand
and to consider this research and the consent form carefully as long as you feel is necessary before you
make a decision.
If you have any questions regarding this study or in case of study-related injuries, you should contact the Study
Physician, Dr. David Matuskey, at (203) 370-1403 (pager), or (203) 737-6316 (office).
Page 21 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015

Approved - Valid through 07-APR-2016

HIC#:1502015328

Authorization and Permission

I have read this form and have decided to participate in the project described above. Its general purposes, the
particulars of my involvement and possible hazards and inconveniences have been explained to my satisfaction.
My signature also indicates that I have received a copy of this consent form.
By signing this form, I give permission to the researchers to use [and give out] information about me for the
purposes described in this form. By refusing to give permission, I understand that I will not be able to be in this
research.
Name of Subject:_____________________________

Signature:___________________________________
Date:______________________________________
___________________________________________
Signature of Principal Investigator
or
___________________________________________
Signature of Person Obtaining Consent

___________________
Date
___________________
Date

If after you have signed this form you have any questions about your privacy rights, please contact the Yale
Privacy Officer at 203/432-5919.
If you have further questions about this project or if you have a research-related problem, you may contact the
Principal Investigator, Richard E. Carson, at (203) 737-2814. If you would like to talk with someone other than
the researchers to discuss problems, concerns, and questions you may have concerning this research, or to
discuss your rights as a research subject, you may contact the Yale Human Investigation Committee at (203)
785-4688.

Page 22 of 22

APPROVED BY THE YALE UNIVERSITY HIC ON 23 JULY 2015

Version #2 June 24, 2015