Assessment of the Biodistribution and Safety of [18F]GTP1 in Healthy Japanese Subjects
Phase: PHASE1
Conditions: Alzheimer Disease
Sponsor: Genentech, Inc.

 
Official Title: Assessment of the Biodistribution and Safety of [18F]GTP1 in Healthy 
Japanese Subjects 
NCT Number: NCT04394845 
Document Date: Protocol Version 3: 10-July-2020 
 
 

PROTOCOL FOR RESEARCHINVOLVINGHUMANSUBJECTS 
 
 
 
Title of Project: 
Assessment of the Biodistribution and Safety of [18F]GTP1 in 
Healthy Japanese Subjects 
 
Protocol No: 
GN42043 
Version No.& Date: 
V3.0 ; 09-Jul-2020 
Sponsor: 
Genentech, Inc. 
1 DNA Way 
South San Francisco, CA 94080-4990 U.S.A. 
United States 
 
Principal Investigator: 
, MD, PhD 
60 Temple Street, 8th Floor 
New Haven, CT 06510 
(203) 401-4300 (24-hour pager) 
Other Investigators: 
, PA-C 

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TABLE OF CONTENTS 
SPONSOR APPROVAL ............................................................................................................................................................................ 2 
INVESTIGATOR SIGNATURE .............................................................................................................................................................. 3 
TABLE OF CONTENTS ........................................................................................................................................................................... 4 
PROTOCOL SYNOPSIS ........................................................................................................................................................................... 8 
1. 
Introduction ............................................................................................................................................................................. 15 
1.1. 
Background ......................................................................................................................................................................... 15 
1.2. 
Human Safety and Tolerability of [18F]GTP1 ................................................................................................ 16 
2. 
Study Objectives and Endpoints ......................................................................................................................................... 16 
3. 
Investigational Plan ...................................................................................................................................................... 17 
3.1. 
Study Design ....................................................................................................................................................................... 17 
3.2. 
Study Rationale ................................................................................................................................................................. 18 
3.3. 
Risk/Benefit for this Study .......................................................................................................................................... 19 
4. 
Population ................................................................................................................................................................................. 19 
4.1. 
Inclusion Criteria .............................................................................................................................................................. 19 
4.2. 
Exclusion Criteria ............................................................................................................................................................. 20 
5. 
Treatment ................................................................................................................................................................................. 21 
5.1. 
Investigational Agent ......................................................................................................................................................... 21 
5.2. 
Treating the Subject ....................................................................................................................................................... 21 
5.2.1. 
Study Drug Supply and Storage ...................................................................................................................... 21 
5.2.2. 
Administration of Investigational Agent ...................................................................................................... 22 
5.2.3. 
Concomitant Treatment ................................................................................................................................. 22 
5.2.4. 
Discontinuation of Study Treatment and Premature Subject Withdrawal ............................. 22 
5.2.5. 
Study Completion and Post-Study Treatment ..................................................................................... 22 
6. 
Visit Schedule and Assessments ......................................................................................................................................... 23 
6.1. 
Study Schedule .................................................................................................................................................................. 23 
6.1.1. 
Screening Visit ......................................................................................................................................................... 23 
6.1.2. 
Whole-body [18F]GTP1 PET Imaging Visit .............................................................................................. 23 
6.1.3. 
Safety Follow-up Phone Visit .......................................................................................................................... 25 
6.2. 
Whole-body [18F]GTP1 PET Imaging Procedures ...................................................................................... 25 
6.3. 
Urine Collection for Dosimetry Analysis ............................................................................................................. 25 
6.4. 
Safety Evaluations ........................................................................................................................................................... 25 

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6.4.1. 
Physical Examination ...................................................................................................................................... 25 
6.4.2. 
Vital Signs ....................................................................................................................................................................... 26 
6.4.3. 
Height and Weight ................................................................................................................................................ 26 
6.4.4. 
Laboratory Evaluations ...................................................................................................................................... 26 
6.4.4.1. 
Hematology ........................................................................................................ 26 
6.4.4.2. 
Clinical chemistry .............................................................................................. 26 
6.4.4.3. 
Urinalysis .............................................................................................................. 26 
6.4.4.4. 
Serology ................................................................................................................ 27 
6.4.4.5. 
Pregnancy testing ............................................................................................. 27 
6.4.5. 
Electrocardiogram (ECG) .................................................................................................................................. 27 
7. 
Safety Monitoring ....................................................................................................................................................................... 28 
7.1. 
Adverse Events ........................................................................................................................................................ 28 
7.1.1. 
AE Definition ....................................................................................................................................................... 28 
7.1.2. 
SAE Definition ..................................................................................................................................................... 28 
7.1.3. 
Adverse Events of Special Interest Definition ...................................................................................... 29 
7.1.4. 
Cases of Accidental Overdose or Medication Error ........................................................................ 29 
7.1.5. 
Treatment of AEs .......................................................................................................................................... 30 
7.1.6. 
Relationship of AEs to the Study Drug .................................................................................................... 31 
7.2. 
Serious Adverse Event and Adverse Event of Special Interest Reporting ......................................... 31 
7.3. 
Methods for Capturing and Assessing Safety Parameters ....................................................................... 32 
7.4. 
Procedures for Recording Adverse Events .................................................................................................. 32 
7.4.1. 
Diagnosis versus Signs and Symptoms.............................................................................................. 32 
7.4.2. 
Adverse Events That are Secondary to Other Events .................................................................... 32 
7.4.3. 
Deaths .......................................................................................................................................................................... 32 
7.5. 
Post-Study Adverse Events ................................................................................................................................ 32 
8. 
Data Review and Database Management ....................................................................................................................... 33 
8.1. 
Site Monitoring .................................................................................................................................................................. 33 
8.2. 
Database Management and Quality Control....................................................................................................... 33 
9. 
Data Analysis................................................................................................................................................................................. 33 
9.1. 
Subject Demographics and Other Baseline Characteristics ..................................................................... 33 
9.2. 
Imaging Analysis and Statistics ................................................................................................................................ 33 
9.3. 
Safety Analysis and Statistics ................................................................................................................................. 34 

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9.4. 
Sample Size .................................................................................................................................................................... 35 
10. 
Regulatory and Ethical Considerations .................................................................................................................... 35 
10.1. 
Regulatory and Ethical Compliance ............................................................................................................... 35 
10.2. 
Informed Consent Procedures .......................................................................................................................... 35 
10.3. 
Confidentiality .............................................................................................................................................................. 35 
10.4. 
Responsibilities of the Investigator and IRB .............................................................................................. 35 
11. 
References ............................................................................................................................................................................... 36 
12. 
Appendix 1 – World Health Organization Toxicity Grading Scale ............................................................ 38 
13. 
Appendix 2 – Protocol Summary of Changes, Amendment 1 ................................................................. 42 
14. 
Appendix 3 – Protocol Summary of Changes, Amendment 2 ................................................................. 43 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
Aβ 
Amyloid beta 
AD 
Alzheimer's  disease 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine  transaminase 
AST 
Aspartate  aminotransferase 
BP 
Blood pressure 
CRF 
Case report form 
CT 
Computed tomography 
CN 
Cognitive normal 
ECG 
Electrocardiogram 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GI 
Gastrointestinal 
GMP 
Good  Manufacturing Practice 
HAT 
Human alimentary tract 
HPLC 
High-performance liquid  chromatography 
ICH 
International Conference on Harmonization 
ICRP 
International Commission on  Radiological Protection 
IHC 
Immunohistochemistry 
IRB 
Institutional Review  Board 
IV 
Intravenous 
MBq 
Megabequerels 
mCi 
Milicuries 
MIRD 
Medical Internal Radiation Dose 
NDOB 
Name date of birth 
OLINDA 
Organ Level Internal Dose Assessment 
OTC 
Over the counter 
PET 
Positron emission tomography 
PMOD 
Software for biomedical image quantification 
PSP 
Progressive  supranuclear palsy 
QA 
Quality assurance 
ROI 
Region of interest 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SUV 
Standard uptake value 
TAC 
Time-activity  curve 
VOI 
Volume of interest 
ULN 
Upper limits of normal 

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PROTOCOL SYNOPSIS 
TITLE 
Assessment of the Biodistribution  and Safety of [18F]GTP1 in 
Healthy Japanese Subjects 
TEST PRODUCT 
[18F]GTP1 
CLINICAL  PHASE 
1 
INDICATION 
Alzheimer's  Disease 
TRIAL  OBJECTIVES 
The overall goal of this protocol is to evaluate the biodistribution of 
[18F]GTP1  as a tau targeted radiopharmaceutical. The specific 
objectives are: 
● 
To determine the radiation dosimetry of [18F]GTP1  in 
Japanese subjects 
● 
To assess the safety and tolerability of a single dose of 
[18F]GTP1 in Japanese subjects 
STUDY  DESIGN 
Up to 6 healthy Japanese subjects (with at least 1 male and 1 female) 
will  be recruited from the healthy controlpopulation by advertising 
and community outreach. 
This study will  be performed in healthy control research participants. 
All study procedures will  be conducted at Invicro in New Haven, 
CT. All subjects will  undergo written informed consent and a 
screening evaluation including baseline clinical  laboratory testing 
and baseline physicalevaluation. 
On the day prior to imaging subjects will  be admitted for overnight 
confinement. On the day of imaging, subjects will  be asked to 
undergo a single  bolus injection of [18F]GTP1 followed by serial 
whole-body positron emission tomography (PET) imaging scans of 
up to 6 hours. Immediately following the [18F]GTP1 administration a 
series  of approximately nine whole-body PET images from the 
vertex of the head to the thighs will  be obtained. The subject would 
have at least two breaks during the scanningsession.  An isotope 
transmission scan will  be performed each time the subject lies on the 
camera. Commencingwith radiotracer injection, urine collection  will 
be initiated. Standard Medical Internal Radiation Dose (MIRD) 
assumptions will be incorporated in dosimetry models for 
determination of radiation absorbed doses to target organs and 
whole-body. Urine  samples collected over the imaging period will  be 
evaluated to measure the excretion of [18F]GTP1 through the urinary 
tract. 
A follow-up phone call to the subject will  be conducted within 4 
days (± 2 days) post-injection of [18F]GTP1 to confirm subject well- 
being and to collect information about any new adverse events 
(AEs). 
INCLUSION/EXCLUSION 
CRITERIA 
Healthy volunteer subjects who are medically stable and meet the 
inclusion criteria and do not meet any of the exclusion criteria will 
be eligible  for enrollment into the study. 
Inclusion  Criteria 
● 
Understand the study procedures and agree to participate by 
providing written  informed consent. 
● 
Are willing  and able to comply with all study procedures and 
restrictions. 
WHO 
World  Health Organization 

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● 
Are males or females > 18 years of age. 
● 
Are in good health as determined by the Investigator based on 
clinical  evaluations including past medical history, physical 
examination, vitalsigns,  electrocardiogram (ECG),  and 
laboratory tests at screening  and prior to radiopharmaceutical 
administration. 
● 
For women of childbearing potential, agreement to remain 
abstinent (refrain from heterosexualintercourse) or use 
contraception, and agreement to refrain from donatingeggs, 
as defined below: 
o A woman is considered to be of childbearing potential 
if she is postmenarchal, has not reached a 
postmenopausalstate (12 continuous months of 
amenorrhea with no identified cause other than 
menopause), and is not permanently infertile due to 
surgery (ie,  removalof ovaries, fallopian tubes, and/or 
uterus) or another cause as determined by the 
Investigator (eg, Müllerian agenesis). The definition of 
childbearing potentialmay be adapted for alignment 
with local guidelines  or regulations. 
o 
Women of childbearing potentialmust remain abstinent 
or use contraceptive methods with a failure rate of <1% 
per year during the treatment period and for 30 days 
after the final dose of [18F]GTP1. Women must refrain 
from donatingeggs  during this same period. 
o 
Examples of contraceptive methods with a failure rate 
of <1% per year include bilateral tuballigation, male 
sterilization,  hormonalcontraceptives that inhibit 
ovulation, hormone-releasing intrauterine devices,  and 
copper intrauterine devices. 
o 
The reliability  of sexualabstinence should be evaluated 
in relation to the duration of the clinical trial and the 
preferred and usuallifestyle  of the subject. Periodic 
abstinence (eg,  calendar, ovulation, symptothermal, or 
postovulation methods) and withdrawalare not 
adequate methods of contraception. If required per local 
guidelines  or regulations, locally recognized adequate 
methods of contraception and information about the 
reliability  of abstinence will be described in the local 
informed consent form 
● 
Male subjects with  partners of childbearing potentialmust 
commit to the use of two methods of contraception, one of 
which is a barrier method (ie, condom), for the study duration 
and 90 days after the last dose. 
● 
Male subjects must not donate sperm for the duration of the 
study and 90 days after the last dose. 
● 
Subjects must have both Japanese parents and all Japanese 
grandparents (self-reported). 
Exclusion Criteria 
● 
The subject has a clinically  significant abnormallaboratory 
value and/or clinically  significant unstable medical or 
psychiatric illness. 

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● 
The subject is currently exposed to nicotine products or had 
regular nicotine exposure within a six-month period, to be 
verified by urine cotinine screening. 
● 
History of drug or alcohol abuse within 12 months prior to 
screening, or evidence of such abuse as indicated by the 
laboratory assays conducted duringthe screening visit. 
● 
The subject has evidence of clinically  significant 
gastrointestinal (GI),  cardiovascular, hepatic, renal, 
hematological, neoplastic, endocrine, neurological, 
immunodeficiency, pulmonary, or other disorder or disease. 
● 
Prior participation in other research protocols or clinical care 
in the last year in addition to the radiation exposure expected 
from participation in this clinical study, such that radiation 
exposure exceeds the effective dose of 50 mSv, which would 
be above the acceptable annuallimit established by the US 
Federal Guidelines. 
● 
Use of any prescription drugs (except approved forms of birth 
control noted in Section 5.2.3), herbal supplements, within 
four weeks prior to initial dosing. 
● 
Use of over the counter (OTC) medication (except 
acetaminophen), dietary supplements, or vitamins, within  two 
weeks prior to initial dosing. 
● 
Has a known hypersensitivity to any component of the 
formulation of [18F]GTP1  or related compounds. 
● 
Major surgery, or donation or loss of 400 mL or more of 
blood within four (4) weeks prior to initial dosing, or longer if 
required by local regulation. 
● 
Have a history or presence of any significant cardiovascular, 
respiratory, hepatic, renal, GI, endocrine, or neurological 
disorders which, in the opinion of the Investigator, are capable 
of altering the absorption, metabolism, or elimination of drugs 
or posing a health risk to participate in the study. 
● 
History of immunodeficiency diseases, including a positive 
HIV test result. 
● 
A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C 
antibody test result. 
● 
Positive pregnancy test result, if female. Women without 
documentation of non-childbearing potentialwill  also receive 
pregnancy testing. 
● 
Women who are lactating and breastfeeding. 
● 
Unsuitable veins for repeated venipuncture. 
● 
Subject is, in the opinion of the Investigator, unsuitable in any 
other way to participate in this study. 
LENGTH OF STUDY 
For each subject participating, the duration of study participation 
will  be up to 36 days. The completion of this study protocol requires 
each subject to complete three visits: Screening Visit, a single 
[18F]GTP1 Whole-body PET Imaging Visit  and a Follow-up  Phone 
Call. The screening visit  will  include vital signs,  ECG and a physical 
exam. In addition, each subject will  complete clinical assessments 
and clinical safety labs to ensure the subject is medically stable to 
complete the study protocol. The screening procedures will  occur 

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within 30 days of the imaging visit. After subjects have met all study 
entry criteria, subjects will  participate in a single  [18F]GTP1  PET 
whole-body imaging session. The Follow-up  Phone Call for AE 
assessment will  occur within approximately 4 days (± 2 days) 
following the [18F]GTP1 PET imaging. 
OUTCOMES 
WHOLE-BODY 
BIODISTRIBUTION  OUTCOME 
MEASURES 
SAFETY  OUTCOME  MEASURES 
The following parameters will be evaluated: 
● 
Totalsource organ counts based on individualized organ 
volumes of interest (VOIs) 
● 
Source organ uptake and washout with calculation of the total 
number of disintegrations (or residence time) using the area 
under the time-activity curve divided by the injected dose of 
radiopharmaceutical 
Radiation absorbed dose estimates based on the MIRD methodology 
utilizing  urine data and International Commission on Radiological 
Protection (ICRP) GI tract kinetics 
Safety will  be evaluated by review of AEs, clinical laboratory tests, 
vital signs, physical findings, and ECG findings at screening and 
intervals throughout the imaging visit. A safety Follow-up  Phone 
Call within 4 days (± 2 days) after imaging will  assess for AEs and 
concomitant  medications. 
INVESTIGATIONAL   AGENT 
All subjects will  receive a single injection of [18F]GTP1, a PET 
radioligand selective for tau, once during the course of study 
participation. (See Section 5.2.2 for full details on [18F]GTP1 
administration.) 
PROCEDURES 
SCREENI NG:  Subject eligibility   will  be evaluated during screening. 
The Whole-body [18F]GTP1 PET Imaging Visit  will  occur within  30 
days of screening. Screening will  include informed consent, medical 
history and demography collection, review of medications, review of 
inclusion and exclusion criteria, urine drug and alcoholtesting, vital 
signs, ECG, physical exam, and clinical labs to ensure the subject is 
medically stable to complete the study. All women of childbearing 
potentialmust have a negative serum pregnancy test. 
WHOLE-BODY  [18F]GTP1 PET IMAGING VISIT: [18F]GTP1 will 
be synthesized in Invicro’s Good Manufacturing Practice (GMP) 
chemistry laboratory under an approved IND. 
All women of childbearing potentia lwill  have a urine pregnancy test 
determined to be negative within  24 h before PET tracer injection. 
Whole-body PET imaging will  be performed, acquiring an emission 
scan for each bed position and an isotope transmission scan or 
computed tomography (CT) scan each time the subject lies on the 
camera. Subjects will  first receive an isotope transmission scan or 
CT scan. Then subjects will  receive a bolus intravenous (IV) 
administration of [18F]GTP1. Immediately following the [18F]GTP1 
administration, a series  of whole-body PET images from the vertex 
of the head to the thighs will be obtained over a period of up to 6 
hours. The subject will  have at least two breaks over a six-hour 
scanning session. Commencingwith  radiotracer injection, urine 
collection will  be initiated. Standard MIRD assumptions will  be 

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STATISTICAL  METHODS 
incorporated in dosimetry models for determination of radiation 
absorbed doses to target organs and whole-body. Urine samples 
collected over the imaging period will  be evaluated to measure the 
excretion of [18F]GTP1  through the urinary tract. During the 
imaging, safety assessments will be performed, including ECGs, 
clinical labs, and vitalsign  measurements. 
If a PET scan is cancelled due to synthesis failure of [18F]GTP1 or 
camera problems, injection of [18F]GTP1 will  not occur, and the 
scanning procedures listed above will be performed on another day 
in the same subject. 
FOLLOW-UP  PHONE CALL: A follow-up phone call for AE 
assessment will  occur within 4 days (± 2 days) post-injection 
following the [18F]GTP1 PET scan imaging. 
DEMOGRAPHICS 
All data for background and demographic variables will be listed. 
For these parameters, summary statistics will  be provided by subject. 
Relevant medicalhistory, current medical conditions, results of 
laboratory screens, and any other relevant information will  be listed 
by subject. 
SAFETY 
Analysis of safety parameters will include all vital signs, ECG, 
clinical laboratory tests, physical findings, and AE data listed by 
subject and visit/time. Summary statistics will  be provided by 
visit/time. 
IMAGING 
 
SAMPLE  SIZE JUSTIFICATION 
Descriptive  statistics will  be applied to describe biodistribution of 
[18F]GTP1 by organ. 
The sample size for this study was determined by practical 
considerations and is not based on statistical power calculations. Up 
to 6 evaluable subjects (with at least 1 male and 1 female) will 
complete this study. 
While the sample size is small, this should be adequate to determine 
biodistribution and dosimetry calculations of [18F]GTP1 in Japanese 
subjects. 

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Table 1: Schedule of Assessments 
 
Screening Visit 
[18F]GTP1 Whole-body PET Imaging Visit 
Follow-up 
Phone Call 
Day 
Within 
30 days 
of Imaging visit 
Check-in 
Within 30 days of screening 
4 days 
(± 2 days) 
post-injection 
Time in relation to 
radioligand injection 
Day prior 
to PET 
Imaging 
Pre- 
injection 
Imaging 
period 
Post scan 
Inclusion/Exclusion 
Criteria 
X 
X 
Informed Consent 
X 
Medical History 
X 
Demography 
X 
Physical  Examination 
X 
X1 
Height and Weight 
Measurement2 
X 
X 
Vital Signs3 
X 
X 
X 
X 
ECG4 
X 
X 
X 
X 
Hematology, Blood 
Chemistry, Serology  & 
Urinalysis5 
X 
X 
X 
Serum Pregnancy Test 
(if  applicable)6 
X 
Urine  Pregnancy Test 
(if  applicable)6 
X 
Urine Drug, Alcohol, 
and Cotinine Screen 
X 
X 
[18F]GTP1  Injection7 
X 
Whole-body PET 
Imaging 
X 
Urine  Collection8 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
Concomitant 
Medications 
X 
X 
X 
X 

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1 The physicalwill  be symptom-directed. 
2 Height will  only be measured during screening. 
3 Vital signs (systolic  and diastolic blood pressure [BP], respiratory rate, and pulse rate) will  be obtained after at least 5 
minutes of rest in the supine position during screening and at the Whole-body [18F]GTP1 PET Imaging Visit  at the 
following timepoints: pre-injection and approximately 20, 50, 80, and 120 minutes following injection. Oral body 
temperature will be obtained during screening and at the Whole-body [18F]GTP1 PET Imaging Visit  at the following 
timepoints: pre-injection  and at the completion of imaging. 
4 Electrocardiogram (ECG) will  be obtained during screening and at the Whole-body [18F]GTP1 PET Imaging Visit  at the 
following timepoints: pre-injection, approximately 25 and 45 minutes following  injection, and at the completion of the 
imaging session. 
5  Safety labs (hematology, blood chemistry and urinalysis) will  be obtained during screening and at the Whole-body 
[18F]GTP1 PET Imaging Visit  at the following timepoints: pre-injection and at the completion of imaging. Serology  (HIV 
and Hepatitis B & C testing) will  be performed at screening only. Hematology will  include hemoglobin, hematocrit, red 
blood cell count, white blood cell count with differential (absolute count and percentage), and platelet count. Blood 
chemistry assessments will  include albumin, albumin/globulin ratio (calculated), alkaline phosphatase, alanine 
transaminase (ALT), aspartate aminotransferase (AST), bun/creatinine ratio (calculated), calcium, carbon dioxide, 
chloride, creatinine with glomerular filtration rate (GFR) estimated, globulin (calculated), glucose, potassium, sodium, 
totalbilirubin, totalprotein, urea nitrogen. Urinalysis will include leukocytes, nitrites, urobilinogen, protein, pH, blood 
(erythrocytes), specific gravity, ketone, bilirubin  and glucose 
6 For women of childbearing potential, a serum pregnancy test will  be performed during screening. Urine pregnancy test 
will  be done at the Whole-body [18F]GTP1 PET Imaging Visit.  The test will  occur within 24 hours prior to the injection  
of [18F]GTP1  injection. Women without documentation of non-childbearingpotentialwill  also receive pregnancy testing. 
7  Approximately, but not exceeding, 370 MBq (10 mCi) of [18F]GTP1 will  be injected IV by bolus injection. 
8  Urine samples will  be collected over the imaging period and at scan completion to measure the excretion of [18F]GTP1 
through the urinary tract. 

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1. 
INTRODUCTION 
1.1. 
Background 
Molecular imaging biomarkers have the potential to play a key diagnostic role in tauopathies. 
Tau protein has been identified as one of the key pathological features of Alzheimer’s disease 
(AD) (Wood et al., 1986; Grundke et al., 1986; Kosik et al., 1986). Given the role of tau protein 
in the pathology of AD and other non-AD tauopathies, expanding neuroimaging biomarkers to 
include a tau radiotracer is a logical next target offering the potential to improve our 
understanding of the pathological process in AD and other tauopathies. Tau is the primary protein 
composing neurofibrillary tangles and unlike amyloid β (Αβ) deposition, post-mortem        
studies have shown that neurofibrillary tangle density correlates with neurodegeneration and 
cognitive impairment (Duyckaerts et al., 1987, 1990; Delaere et al., 1989; Arriagada et al., 1992; 
McLean et al., 1999). Thus, a positron emission tomography (PET) imaging agent that binds to 
aggregated tau has the potential to serve as a biomarker for disease severity or neurodegeneration 
and may be useful for monitoring disease progression in therapeutic trials. 
Development of a tau radiotracer would provide a useful tool to evaluate tau specific therapeutics 
for both AD and non-AD tauopathies. Tau hyperphosphorylation occurs as a result of an 
imbalance of the kinase and phosphatase activities, which normally tightly regulate its 
phosphorylation. In addition to this pathogenic hyperphosphorylation, tau dissociates from 
microtubules and self-aggregates to form insoluble oligomers ultimately progressing to the 
macroscopic tangles evident in AD and non-AD tauopathies. Potential interventions for 
tauopathies might include the inhibition of kinases responsible for hyperphosphorylation and 
many candidate kinases are currently under investigation (Churcher, 2006). The search for these 
treatments is paralleled by a pursuit for a means to identify those patients best suited for the 
therapy and methods to non-invasively determine the efficacy of treatments with the potential to 
reduce tau. 
Until recently, post-mortem examination of brain tissues was the only means available for 
directly evaluating the changes occurring in the brain in AD and non-AD tauopathies. In the last 
decade, the development of highly specific techniques for imaging the brain in AD and other 
dementias has expanded our ability to measure the process of the disease over time in a living 
individual. Briefly, these techniques involve intravenous (IV) administration of radioactively- 
labeled compounds which bind to selective target sites in brain. PET is able to detect the spatial 
distribution of the radioactive compound in the brain and can be used as an objective, sensitive, 
and accurate method to quantify the concentration of the targets site in different brain regions. 
Using these PET techniques, Aβ aggregates have been successfully imaged in several studies in 
AD patients using high affinity C-11 and 18F-labeled PET tracers (PIB and florbetapir, AV-1) 
(Klunk et al., 2004ab; Clark et al, 2011; Hyman 2012). Now there are multiple studies 
comparing amyloid PET scans to histopathologic assessment that support the relationship 
between PET amyloid imaging results and cortical neuritic plaque density (Stephens 2014; 
Ruiqig N 2013; Leinonen, 2008; Sojkova, 2011). 
The ability to image brain amyloid has offered an important advance for the diagnosis of 
neurodegenerative conditions. In contrast to Aβ neuritic plaques, the density and distribution of 

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phosphorylated tau, aggregated in neurofibrillary tangles, increases with AD-related cognitive 
impairment and correlates with neurodegeneration (Dickson et al., 1997; Duyckaerts et al., 
1987). Thus, the development of PET imaging agent that binds to aggregated tau offers the 
potential to improve our understanding of the molecular mechanism of neurofibrillary 
degeneration and is critical to developing a rational therapeutic treatment of AD and related 
tauopathies. 
[18F]GTP1 (also known as [18F]G02941054, and referred to as [18F]MNI-798 in some previous 
clinical studies) has been developed as a positron emitting radiopharmaceutical for in vivo 
imaging of tau protein aggregates. In a cross-sectional study of cognitively normal and 
prodromal to moderate AD patients, [18F]GTP1 exhibited good brain penetration and rapid 
washout, excellent test-retest reproducibility, and favorable radiation dosimetry profile. In 
general, SUVR values increased with disease severity and differentiated between AD and 
cognitive normal (CN) cohorts and between brain regions predicted to contain high versus low 
tau burden, supporting the use of [18F]GTP1 PET imaging as a biomarker of tau pathology in AD 
(Bohórquez et al.). The study drug is referred to as [18F]GTP1 throughout the protocol and 
informed consent documents given that the radiopharmaceutical bears the label of [18F]GTP1 and 
that the names are synonymous. 
 
1.2. 
Human Safety and Tolerability of [18F]GTP1 
As of 1 February 2019, [18F]GTP1 has been evaluated in three completed clinical studies (e0040, 
e0048, and e0049) and is being evaluated in five ongoing studies: Study GN30009, Substudy 
WN29922/WN39658, Study GN39763, Substudy BN29552/BN29553, and Study GN40040. All 
studies in the clinical development program have been conducted in accordance with the 
principles of Good Clinical Practice. A total of 23 healthy volunteers, 470 patients with AD, and 
3 patients with progressive supranuclear palsy (PSP) have been exposed to at least one dose of 
[18F]GTP1, and there have been a total of 702 doses in total across all studies. Two of the 470 
patients with AD were enrolled in more than one study (in Study e0048 and in Study GN30009). 
[18F]GTP1 was found to be generally well tolerated. As of 1 February 2019, no deaths or adverse 
events (AEs) of special interest were reported. One serious adverse event (SAE) was reported in 
Study GN30009: a Grade 3 urinary tract infection, reported in a 
-year-old 
 patient with 
moderate AD; the SAE was assessed as not related to study drug. One 
-year-old 
 patient 
with prodromal AD discontinued the study due to a non-serious moderate headache and non- 
serious cervical neck pain 4 days after a baseline [18F]GTP1 PET scan; both events were  
assessed as not related to study drug. 
 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
The overall goal of this protocol is to evaluate the biodistribution of [18F]GTP1 as a tau targeted 
radiopharmaceutical. 

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Objectives 
Endpoints 
To determine the radiation dosimetry of 
[18F]GTP1 in Japanese subjects 
● Total source organ counts based on 
individualized organ volumes of interest 
(VOIs) 
● Source organ uptake and washout with 
calculation of total number of 
disintegrations (or residence time, or kinetic 
values) using the area under the time- 
activity curve divided by the injected dose 
of radiopharmaceutical 
● Radiation absorbed dose estimates based on 
the MIRD methodology utilizing urine data 
and International Commission on 
Radiological Protection (ICRP) 
gastrointestinal (GI) tract kinetics 
To assess the safety and tolerability of a single 
dose of [18F]GTP1 in healthy Japanese subjects 
Safety will be evaluated by review of: 
● AEs 
● Clinical laboratory tests 
● Vital signs 
● Physical findings 
● ECG findings 
 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Study Design 
This is an open-label study to evaluate the whole-body biodistribution of [18F]GTP1 in up to 6 
evaluable healthy Japanese subjects (with at least 1 male and 1 female) to determine dosimetry 
for future studies. Subjects will be recruited by Invicro from the healthy population by 
advertising and community outreach. This study protocol requires each subject to complete the 
following visits: Screening Visit, Whole-body [18F]GTP1 PET Imaging Visit, and a Follow-up 
Phone Call. Screening evaluations will occur within 30 days of the Whole-body [18F]GTP1 PET 
Imaging Visit and may occur over multiple days. Screening procedures will include signing of 
the informed consent form, review of inclusion and exclusion criteria, collection of medical 
history and medication information, collection of demography information, physical 
examination, height and weight measurement, vital signs (respiratory rate, pulse rate, blood 
pressure [BP] and oral body temperature), laboratory tests (hematology, blood chemistry, and 
urinalysis), ECG, serum pregnancy test (if applicable), and drug and alcohol screening. 
Assessments will determine if the subject is medically stable to complete the study protocol and 
meets the eligibility criteria. 

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Subjects will be confined on the day prior to [18F]GTP1 imaging in the overnight confinement 
unit. On the day of check-in, the subjects will receive a symptom-directed physical assessment, 
drug and alcohol screening, and review of concomitant medications. 
The following day, there will be a review of inclusion and exclusion criteria, a weight 
measurement, a review of concomitant medications, and a urine pregnancy test (if applicable) to 
assess if the subject still meets the eligibility criteria. For the [18F]GTP1 imaging session, a 
catheter will be placed for IV administration of [18F]GTP1. Subjects will receive an IV bolus 
injection of [18F]GTP1 (see Section 5.2.2 for full details on [18F]GTP1 administration). 
Immediately following the [18F]GTP1 administration, a series of whole-body PET images from 
the vertex of the head to the thighs will be obtained over a period of up to 6 hours. The subject 
will have at least two breaks over a six-hour scanning session. An isotope transmission scan or 
computed tomography (CT) scan will be performed each time the subject lies on the camera. 
Commencing with radiotracer injection, urine collection will be initiated. Standard MIRD 
assumptions will be incorporated in dosimetry models for determination of radiation absorbed 
doses to target organs and whole-body. Urine samples collected over the imaging period and at 
the completion of imaging will be evaluated to measure the excretion of [18F]GTP1 through the 
urinary tract. Safety assessments (ie, vital signs, clinical laboratory assessments, and ECGs) will 
be performed during the imaging visit. The subjects will be discharged after all assessments are 
complete. 
AEs will be assessed from screening until the subject discontinues study participation. An 
Investigator or designee will evaluate the subject for AEs prior to discharge from the imaging 
center on the day of the Whole-body [18F]GTP1 PET Imaging Visit. Subjects who experience an 
AE will not be discharged from the imaging center until the event has resolved or stabilized. 
A Follow-up Phone Call to the subject will be conducted within 4 days (± 2 days) post-injection 
of [18F]GTP1, to confirm subject well-being and to collect information about any new AEs. 
 
3.2. 
Study Rationale 
This is an open-label study to evaluate the reliability of using microdoses (less than 10 µg) of 
radiotracer [18F]GTP1 for the evaluation of the whole-body biodistribution of the tracer in 6 
healthy Japanese subjects (with at least 1 male and 1 female). Evaluating a small number of 
healthy subjects is standard to develop dosimetry calculations and to evaluate safety and 
tolerability. While [18F]GTP1 dosimetry studies and safety studies have been performed in 
healthy subject populations, the dosimetry and safety of [18F]GTP1 have not been specifically 
studied in Japanese subjects. 
The development of a PET tracer for tau offers the possibility to utilize such an agent toward the 
development of investigational therapies and the further understanding of the pathophysiology of 
AD and other tauopathies and could therefore provide a societal benefit by accelerating the 
development of new treatments for AD and other tauopathies. 
There is no direct benefit to subjects who participate in this protocol. 

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3.3. 
Risk/Benefit for this Study 
There may be unknown risks to [18F]GTP1, but given that the investigational agent will be 
administered as a single microdose, the risk for a pharmacological effect is considered to be 
minimal. The potential benefit of the agent is the availability of a radiotracer targeting tau protein 
offering the possibility of improvement in diagnostic accuracy of AD and for measuring changes 
in tau with novel AD therapies. The primary risk associated with this study involves radiation 
exposure. The tracer doses used in this study and the experience of the Investigators in the 
execution of PET studies in humans in addition to the potential benefit of the [18F]GTP1 ligand 
for diagnostic uses make the relative risk/benefit ratio quite favorable. 
 
4. 
POPULATION 
The Investigator will ensure that all subjects being considered for the study meet the eligibility 
criteria. Subject selection is to be established by checking through all inclusion/exclusion criteria 
at screening and at the imaging visit. A relevant record (eg, checklist) will be stored with the 
source documentation at the study site. 
The study population will be composed of healthy Japanese subjects (with at least 1 male and 1 
female). Subjects will be enrolled until up to 6 evaluable subjects complete the study. 
 
4.1. 
Inclusion Criteria 
Subjects eligible for inclusion in this study only if they meet all the following criteria: 
● Understand the study procedures and agree to participate by providing written informed 
consent. 
● Are willing and able to comply with all study procedures and restrictions. 
● Are males or females > 18 years of age. 
● Are in good health as determined by the Investigator based on clinical evaluations including 
past medical history, physical examination, vital signs, ECG, and laboratory tests at 
screening and prior to radiopharmaceutical administration. 
● For women of childbearing potential, agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, 
as defined below: 
o A woman is considered to be of childbearing potential if she is postmenarchal, has not 
reached a postmenopausal state (12 continuous months of amenorrhea with no identified 
cause other than menopause), and is not permanently infertile due to surgery (ie, 
removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the 
Investigator (eg, Müllerian agenesis). The definition of childbearing potential may be 
adapted for alignment with local guidelines or regulations. 
o Women of childbearing potential must remain abstinent or use contraceptive methods 
with a failure rate of <1% per year during the treatment period and for 30 days after the 

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final dose of [18F]GTP1. Women must refrain from donating eggs during this same 
period. 
o Examples of contraceptive methods with a failure rate of <1% per year include bilateral 
tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, 
hormone-releasing intrauterine devices, and copper intrauterine devices. 
o The reliability of sexual abstinence should be evaluated in relation to the duration of the 
clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (eg, 
calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not 
adequate methods of contraception. If required per local guidelines or regulations, 
locally recognized adequate methods of contraception and information about the 
reliability of abstinence will be described in the local informed consent form. 
● Male subjects with partners of childbearing potential must commit to the use of two methods 
of contraception, one of which is a barrier method (ie, condom), for the study duration and 90 
days after the last dose. 
● Male subjects must not donate sperm for the duration of the study and for 90 days after the 
last dose. 
● Subjects must have both Japanese parents and all Japanese grandparents (self-reported). 
4.2. 
Exclusion Criteria 
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study: 
● The subject has a clinically significant abnormal laboratory value and/or clinically significant 
unstable medical or psychiatric illness. 
● The subject is currently exposed to nicotine products or had regular nicotine exposure within 
a six-month period, to be verified by urine cotinine screening. 
● History of drug or alcohol abuse within 12 months prior to screening, or evidence of such 
abuse as indicated by the laboratory assays conducted during the screening visit. 
● The subject has evidence of clinically significant GI, cardiovascular, hepatic, renal, 
hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other 
disorder or disease. 
● Prior participation in other research protocols or clinical care in the last year in addition to 
the radiation exposure expected from participation in this clinical study, such that radiation 
exposure exceeds the effective dose of 50 mSv, which would be above the acceptable annual 
limit established by the US Federal Guidelines. 
● Use of any prescription drugs (except approved forms of birth control noted in Section 5.2.3), 
herbal supplements, within four weeks prior to initial dosing. 
● Use of over the counter (OTC) medication (except acetaminophen), dietary supplements, or 
vitamins, within two weeks prior to initial dosing. 
● Has a known hypersensitivity to any component of the formulation of [18F]GTP1 or related 
compounds. 

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● Major surgery, or donation or loss of 400 mL or more of blood within four (4) weeks prior to 
initial dosing, or longer if required by local regulation. 
● Have a history or presence of any significant cardiovascular, respiratory, hepatic, renal, GI, 
endocrine, or neurological disorders which, in the opinion of the Investigator, are capable of 
altering the absorption, metabolism, or elimination of drugs or posing a health risk to 
participate in the study. 
● History of immunodeficiency diseases, including a positive HIV test result. 
● A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result. 
● Positive pregnancy test result, if female. Women without documentation of non-childbearing 
potential will also receive pregnancy testing. 
● Women who are lactating and breastfeeding. 
● Unsuitable veins for repeated venipuncture. 
● Subject is, in the opinion of the Investigator, unsuitable in any other way to participate in this 
study. 
 
5. 
TREATMENT 
5.1. 
Investigational Agent 
[18F]GTP1is a clear solution formulated for IV injection. [18F]GTP1 is formulated in 0.9% 
sodium chloride injection containing ethanol and sodium ascorbate. The final product bears a 
label with the following items: total activity (mCi), volume (mL), strength (mCi/mL), calibration 
date and time, batch number, study ID and shelf life. [18F]GTP1 will be stored at ambient 
temperature in its original container. 
[18F]GTP1 is supplied as a sterile non-pyrogenic solution in sterile borosilicate glass vials with 
gray butyl septa and aluminum ring seals. The vial is contained within an outer lead or tungsten 
shield (“pig”) to protect from γ radiation. 
5.2. 
Treating the Subject 
 
5.2.1. 
Study Drug Supply and Storage 
The investigational agent, the radiopharmaceutical [18F]GTP1, will be produced in the Invicro 
radiochemistry facility at 60 Temple Street, New Haven, CT. Quality control testing includes 
strength by gamma assay, radiochemical purity and identity (HPLC), drug mass and total 
impurity quantification, pH, visual inspection, pyrogenicity and sterility by compendial tests. 
The final drug product is provided as a clear, sterile solution in a 30 mL glass vial. The vial is 
contained within a secondary lead or tungsten radiation shield and may be stored upright at 
ambient temperature and humidity until administration. The investigational agent must be used 
within the expiration time (10 hours). 

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5.2.2. 
Administration of Investigational Agent 
Study center personnel will administer [18F]GTP1 IV as a bolus injection. Prior to PET imaging, 
subjects will have an IV catheter (for radiotracer administration) inserted according to standard 
clinical practice.  Each subject will receive a single injection of [18F]GTP1. The radioligand, 
[18F]GTP1, will be injected IV at a dose of not more than 370 MBq (≤10 mCi), with a maximum 
drug mass dose of 10 µg and maximum volume of 10 mL. The injection will occur as a bolus 
followed by a 10 mL saline flush. Qualified study staff will accompany subjects during PET 
imaging procedures. 
 
5.2.3. 
Concomitant Treatment 
Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, 
and/or OTC medication, dietary supplements (vitamins included) within two (2) weeks prior to 
initial dosing is prohibited. Approved forms of prescription birth control (hormonal 
contraceptives, hormone-releasing intrauterine devices, and copper intrauterine devices) are not 
prohibited and will be documented as a concomitant medication. If needed (ie, an incidental and 
limited need), acetaminophen is acceptable, but must be documented as a concomitant 
medication/significant non-drug therapy. 
5.2.4. 
Discontinuation of Study Treatment and Premature Subject Withdrawal 
The study will be stopped, and no further dosing will occur, pending a full safety review if one or 
more study drug related SAEs are reported. If a subject withdraws or discontinues the study for 
any reason, the subject will be replaced until there are up to (with at least 1 male and 1 female) 
evaluable subjects. 
Subjects may voluntarily withdraw from the study for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, fail to return for visits, or become 
lost to follow-up for any other reason. 
If premature withdrawal occurs for any reason, the Investigator must make every effort to 
determine the primary reason for a subject’s premature withdrawal from the study and document 
this information in the study source. 
Subjects may develop AEs or abnormalities in vital signs, ECG, physical examination, or 
laboratory determinations during their participation in the study. If these occur, the Investigator 
may discontinue a subject from the study if, in his/her clinical judgment, continued participation 
would result in undue risk or further worsening of the condition. 
For subjects who are lost to follow-up (ie, those subjects whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the Investigator should 
show due diligence by documenting attempts to contact the subject, eg, dates of telephone calls, 
registered letters, or other attempts to communicate. 
 
5.2.5. 
Study Completion and Post-Study Treatment 
The study will be complete when the last subject (including replacement subjects) completes the 
final phone visit. 

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The Investigator must provide follow-up evaluation by phone or by clinic visit for all subjects 
who are prematurely withdrawn from the study or must refer them for appropriate ongoing care. 
 
6. 
VISIT SCHEDULE AND ASSESSMENTS 
The full assessment schedule is presented just before Section 1 (Introduction) of this protocol. 
 
6.1. 
Study Schedule 
Study procedures will be performed at three visits: the Screening Visit (may be performed on 
more than one day), Whole-body [18F]GTP1 PET Imaging Visit (including check-in procedures), 
and a Follow-up Phone Call. 
 
6.1.1. 
Screening Visit 
Screening evaluations will occur within 30 days prior to the imaging visit. Before any of the 
screening evaluations are performed for the specific purpose of this study, the subject must 
provide informed consent for this study in compliance with Good Clinical Practice (GCP) and 
IRB requirements. Collection of AE data will begin after the informed consent is signed and will 
continue until the subject discontinues study participation. The screening procedures listed below 
will be performed and documented to assess whether a subject meets inclusion/exclusion criteria: 
● Inclusion and exclusion criteria will be reviewed. 
● A medical history will be taken, and demographics will be recorded. 
● Concomitant medication information will be obtained. 
● Vital signs will be taken after at least 5 minutes of rest in the sitting position, including 
systolic and diastolic BP, pulse rate, respiratory rate (RR), and oral temperature. 
● A complete physical examination will be performed, including height and weight. Rectal, 
breast and genital examinations are not required as part of this examination. 
● A 12-lead ECG will be performed. 
● Blood samples will be collected for clinical chemistry, hematology, HIV, and Hepatitis B and 
C evaluations. 
● Urine sample will be collected for urinalysis, drugs of abuse, alcohol, and cotinine screen. 
● Serum pregnancy test, if female of childbearing potential. 
6.1.2. 
Whole-body [18F]GTP1 PET Imaging Visit 
AEs will be continuously monitored during the Whole-body [18F]GTP1 PET Imaging Visit. All 
eligible subjects will be admitted to the overnight confinement unit on the day prior to the 
Whole-body [18F]GTP1 PET Imaging Visit, which will occur within 30 days of screening. Upon 
check-in, the following procedures will be performed: 
● Urine drug, alcohol, and cotinine screening will be performed. 
● A symptom-directed physical will be performed. 

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● Concomitant medications will be recorded. 
On the day of imaging, procedures will be performed to ensure that the subject still meets the 
eligibility criteria. Prior to imaging the following procedures will be performed: 
● Review of inclusion and exclusion criteria. 
● Subject weight measurement will be obtained. 
● Concomitant medications will be recorded. 
● Vital signs will be taken just prior to imaging (after at least 5 minutes of rest in the sitting 
position), including systolic and diastolic BP, pulse rate, RR, and oral temperature. 
● A 12-lead ECG will be performed. 
● Blood samples will be collected for clinical chemistry and hematology, and a urine sample 
will be collected for urinalysis. 
● Urine pregnancy test, if female of childbearing potential (which must be confirmed as 
negative within 24 hours prior to [18F]GTP1 injection). 
The subject will have a venous catheter placed in the forearm for administration of [18F]GTP1, 
and the subject will lie supine on the camera in preparation for [18F]GTP1 administration. 
[18F]GTP1 will be administered as a bolus IV injection (See Section 5.2.2 for full details on 
[18F]GTP1 administration.). Immediately following [18F]GTP1 administration, PET acquisition 
will begin. PET scans will be acquired over approximately 6 hours, and the subject may have 
two breaks during the scanning period. A CT scan will be performed each time the subject lies 
on the camera. The following procedures will be performed during PET imaging: 
● Vital signs will be taken, including systolic and diastolic BP, pulse rate, and RR (taken after 
at least 5 minutes of rest in the sitting position), approximately 20, 50, 80, and 120 minutes 
post-injection of [18F]GTP1. 
● ECG will be taken approximately 25 and 45 minutes post-injection of [18F]GTP1, and at 
completion of PET imaging. 
● The subject will be asked to void during scheduled breaks in the imaging session. Urine will 
be collected over a period of up to 6 hours throughout the imaging visit for dosimetry 
analysis. 
At the completion of imaging the following procedures will be performed: 
● Vital signs will be taken, including systolic and diastolic BP, pulse rate, RR, and oral body 
temperature (taken after at least 5 minutes of rest in the sitting position). 
● ECG will be taken. 
● Blood samples will be collected for clinical chemistry and hematology, and a urine sample 
will be collected for urinalysis. 
● Urine will be collected for dosimetry analysis. 

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The subject will be discharged after all assessments are complete and the subject has been 
evaluated for AEs. Subjects who experience an AE will not be discharged until the event has 
resolved or stabilized. 
 
6.1.3. 
Safety Follow-up Phone Visit 
Subjects will be contacted by phone approximately 4 days (± 2 days) after the imaging visit, for 
evaluation of AEs and concomitant medications. The subject will be interviewed to determine if 
any new AEs occurred or if there have been any new concomitant medications administered. If 
new medical symptoms have occurred that require further assessment the subject will be asked to 
return to the research clinic for further evaluation. 
 
6.2. 
Whole-body [18F]GTP1 PET Imaging Procedures 
Whole-body PET imaging will be performed on a Biograph 6 PET/CT camera acquiring an 
emission scan for each bed position and a CT scan will be performed each time the subject lies 
on the camera. Subjects will then receive a bolus IV administration of [18F]GTP1 (See Section 
5.2.2 for full details on [18F]GTP1 administration.). Immediately following the [18F]GTP1 
administration a series of whole-body PET images from the vertex of the head to the thighs will 
be obtained over a period of up to 6 hours. The subject will have at least two breaks over a six- 
hour scanning session. 
 
6.3. 
Urine Collection for Dosimetry Analysis 
Commencing with radiotracer injection, urine collection will be initiated. Standard MIRD 
assumptions will be incorporated in dosimetry models for determination of radiation absorbed 
doses to target organs and whole-body. Urine samples collected over the imaging period will be 
evaluated to measure the excretion of [18F]GTP1 through the urinary tract. 
 
6.4. 
Safety Evaluations 
The Investigators will be responsible for monitoring the safety of the subjects that enter this trial. 
Safety will be evaluated by assessment of AEs, clinical safety laboratory tests, ECG, and vital 
signs as outlined in the Schedule of Assessments. 
 
6.4.1. 
Physical Examination 
A complete physical examination will include the examination of general appearance, skin, neck 
(including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, extremities, 
musculoskeletal, and neurological. Rectal, breast and genital examinations are not required as 
part of this examination. A symptom-directed exam will be completed upon admission for the 
Whole-body [18F]GTP1 Imaging Visit; if the subject has new symptoms, only the systems 
relevant to the symptoms will be examined. 
Information for all physical examinations must be included in the source documentation at the 
study site and will be recorded. Significant findings that are present prior to injection of 
[18F]GTP1 will be included in the medical history in the subject's source documents. Significant 
findings made after injection of [18F]GTP1, which meet the definition of an AE must be recorded 
as an AE. 

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6.4.2. 
Vital Signs 
Vital signs include systolic and diastolic BP, RR, oral temperature and pulse rate. Vital signs will 
be obtained during screening and at the Whole-body [18F]GTP1 PET Imaging Visit, as outlined 
in the Schedule of Assessments. Temperature will not be taken while the subject is actively 
undergoing imaging, to avoid any head movement. 
 
6.4.3. 
Height and Weight 
Height and body weight (in indoor clothing) will be measured at screening, and weight will be 
recorded again at the Whole-body [18F]GTP1 PET Imaging Visit. 
6.4.4. 
Laboratory Evaluations 
In the case where a laboratory value is outside the reference range at screening, a decision 
regarding whether the result is of clinical significance or not shall be made by the Investigator 
and shall be based, in part, upon the nature and degree of the observed abnormality. The 
assessment may be repeated once (for the purpose of inclusion) and in any case, prior to 
enrollment/randomization, to rule out laboratory error. 
In all cases, the Investigator will document the clinical considerations (ie, result was/was not 
clinically significant and/or medically relevant) in allowing or disallowing the subject to 
continue in the study. 
Clinically relevant deviations of laboratory test results will be reported as an AE, if the criteria 
are met. Repeated evaluations are mandatory until normalization of the result(s) or until the 
change is no longer clinically relevant. 
 
6.4.4.1. 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential (absolute 
count and percentage), and platelet count will be measured. 
 
6.4.4.2. 
Clinical chemistry 
A standard chemistry panel will be obtained including electrolytes, liver function tests and 
analytes to measure renal function, including albumin, albumin/globulin ratio (calculated), 
alkaline phosphatase, ALT, AST, bun/creatinine ratio (calculated), calcium, carbon dioxide, 
chloride, creatinine with GFR estimated, globulin (calculated), glucose, potassium, sodium, total  
bilirubin, total protein, urea nitrogen. 
 
6.4.4.3. 
Urinalysis 
A midstream urine sample will be obtained, in order to avoid contamination with epithelial cells 
and sediments, and allow proper assessments, and a standard, semi-quantitative dipstick 
performed to evaluate for common urinary tract conditions. Urine dipstick will include 
leukocytes, nitrites, urobilinogen, protein, pH, blood (erythrocytes), specific gravity, ketone, 
bilirubin and glucose. 

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6.4.4.4. 
Serology 
Subjects will be assessed for HIV, Hepatitis B surface antigen, and Hepatitis C antibody results 
during screening. 
 
6.4.4.5. 
Pregnancy testing 
A serum beta-hCG pregnancy test will be performed at screening for females of childbearing 
potential. Urine pregnancy testing will be performed for women of childbearing potential within 
24 hours prior to the administration of a radioligand using a standard kit. 
 
6.4.5. 
Electrocardiogram (ECG) 
A standard 12 lead ECG will be performed. Interpretation of the tracing must be made by a 
qualified physician and documented on the ECG section of the case report form (CRF). Each 
ECG tracing should be labeled with: 
Study number 
Subject NDOB (Name Date of Birth) code 
Subject number 
Date 
Time 
All ECG tracings will be kept in the source documents at the study site. Only clinically 
significant abnormalities will be reported on this page. Clinically significant abnormalities 
should also be recorded as relevant medical history/current medical condition. 
The ECG parameters to be reported in the database will include: 
Date and time of ECG 
Heart rate 
PR interval 
QT interval 
QTc interval 
QTcF interval 
QRS duration 
The overall interpretation will be collected with a Yes/No statement to confirm if any clinically 
significant abnormalities are present which need to be specified further. 
Original ECG tracings, appropriately signed, will be archived at study site. 

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7. 
SAFETY MONITORING 
7.1. 
Adverse Events 
Collection of AEs will commence from the time the subject signs the informed consent to 
participate in the study and continue until the subject discontinues study participation (eg, screen 
failure, study withdrawal, or study completion [ie, Follow-up Phone Call]). 
 
7.1.1. 
AE Definition 
An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition, 
even if the event is not considered to be related to study drug. Study drug includes the 
investigational drug under evaluation during any phase of the study. Medical conditions/diseases 
present before starting study drug are only considered AEs if they worsen after starting study 
drug. Abnormal laboratory values or test results constitute AEs only if they induce clinical signs 
or symptoms, are considered clinically significant, or require therapy. 
The occurrence of AEs should be sought by non-directive questioning of the subject at each visit 
during the study. AEs also may be detected when they are volunteered by the subject during or 
between visits or through physical examination, laboratory test, or other assessments. All AEs 
must be recorded on the Adverse Event Form with information regarding the intensity, 
relationship to study drug (imaging ligand), relationship to study procedures, duration and 
whether it meets the criteria as a SAE. 
The World Health Organization (WHO) toxicity grading scale (see Section 12) will be used for 
assessing AE severity. Table 2 will be used for assessing severity for AEs that are not 
specifically listed in the WHO toxicity grading scale. 
Table 2: Grading of AEs 
 
Grade 
Intensity 
1 
An AE that is mild and transient (<48 hours). No treatment or therapeutic 
intervention is required. 
2 
An AE that is moderate. There is a mild to moderate limitation in activity. Some 
assistance may be needed. No or minimal therapeutic intervention is required. 
3 
An AE that is severe. There is a marked limitation in activity, and some 
assistance is usually required. Medical intervention and/or therapy is required. 
Hospitalization is possible. 
4 
An AE that is life-threatening. There is an extreme limitation in activity, and 
significant assistance is required. Significant medical intervention and/or therapy 
is required, and hospitalization or hospice care is probable. 
 
7.1.2. 
SAE Definition 
An SAE is defined as an event which: 
● is fatal or life-threatening 
● constitutes a congenital anomaly/birth defect 

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● results in persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
● is medically significant, ie, defined as an event that jeopardizes the subject or may require 
medical or surgical intervention to prevent one of the outcomes listed above 
● requires in-patient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
o routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
o elective or pre-planned treatment for a preexisting condition that is unrelated to the 
indication under study and has not worsened since the start of study drug 
 
7.1.3. 
Adverse Events of Special Interest Definition 
Adverse events of special interest (AESI) are required to be reported by the investigator to the 
Sponsor immediately (ie, no more than 24 hours after learning of the event; see Section 7.2 for 
reporting instructions).  AESI for this study are as follows: 
● Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law 
The finding of an elevated ALT or AST (> 3 ULN) in combination with either an 
elevated total bilirubin (2  ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as 
defined by Hy's Law). Therefore, investigators must report as an AE the occurrence of 
either of the following: 
● Treatment-emergent ALT or AST > 3x ULN in combination with total bilirubin 
>2 x ULN 
● Treatment-emergent ALT or AST > 3 x ULN in combination with clinical 
jaundice 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF and reported to the 
Sponsor immediately (ie, no more than 24 hours after learning of the event), either as a 
SAE or an AESI. 
● Suspected transmission of an infectious agent by the study drug, as defined below  
Any organism, virus, or infectious particle (eg, prion protein transmitting transmissible 
spongiform encephalopathy), pathogenic or non-pathogenic, is considered an infectious 
agent. A transmission of an infectious agent may be suspected from clinical symptoms or 
laboratory findings that indicate an infection in a subject exposed to a medicinal product. 
This term applies only when a contamination of the study drug is suspected. 
 
7.1.4. 
Cases of Accidental Overdose or Medication Error 
Accidental overdose and medication error (hereafter collectively referred to as "special 
situations"), are defined as follows: 

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● 
Accidental overdose:  accidental administration of a drug in a quantity that is higher than the 
assigned dose 
● 
Medication error:  accidental deviation in the administration of a drug 
o In some cases, a medication error may be intercepted prior to administration of 
the drug. 
Special situations are not in themselves AEs but may result in adverse events. Each AE 
associated with a special situation should be recorded separately on the Adverse Event eCRF. If 
the associated adverse event fulfills seriousness criteria, the event should be reported to the 
Sponsor immediately (ie, no more than 24 hours after learning of the event; see Section 7.2). For 
[18F]GTP1, adverse events associated with special situations should be recorded as described 
below for each situation: 
● 
Accidental overdose:  Enter the adverse event term. Check the "Accidental overdose" and 
"Medication error" boxes. 
● 
Medication error that does not qualify as an overdose: Enter the adverse event term. Check 
the "Medication error" box. 
● 
Medication error that qualifies as an overdose: Enter the adverse event term. Check the 
"Accidental overdose" and "Medication error" boxes. 
In addition, all special situations associated with [18F]GTP1, regardless of whether they result in 
an adverse event, should be recorded on the Adverse Event eCRF as described below: 
● 
Accidental overdose: Enter the drug name and "accidental overdose" as the event term. 
Check the "Accidental overdose" and "Medication error" boxes. 
● 
Medication error that does not qualify as an overdose: Enter the name of the drug 
administered and a description of the error (eg, wrong dose administered, wrong dosing 
schedule, incorrect route of administration, wrong drug, expired drug administered) as the 
event term. Check the "Medication error" box. 
● 
Medication error that qualifies as an overdose: Enter the drug name and "accidental 
overdose" as the event term. Check the "Accidental overdose" and "Medication error" boxes. 
Enter a description of the error in the additional case details. 
● 
Intercepted medication error: Enter the drug name and "intercepted medication error" as the 
event term. Check the "Medication error" box. Enter a description of the error in the 
additional case details. 
As an example, an accidental overdose that resulted in a headache would require two entries on 
the Adverse Event eCRF, one entry to report the accidental overdose and one entry to report the 
headache.  The "Accidental overdose" and "Medication error" boxes would need to be checked 
for both entries. 
 
7.1.5. 
Treatment of AEs 
All AEs should be treated appropriately. Treatment may include one or more of the following: no 
action taken (ie, further observation only); study drug dosage adjusted/temporarily interrupted; 
study drug permanently discontinued due to this AE; concomitant medication given; non-drug 

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therapy given; subject hospitalized/subject’s hospitalization prolonged. The action taken to treat 
the AE should be recorded on the Adverse Event Form. 
Once an AE is detected, it should be followed until its resolution to baseline grade or better, or 
until it is judged to be stable or permanent by the investigator, or the participant withdraws 
consent. Assessment should be made at each visit (or more frequently, if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat it, and the outcome. 
Information about potential risks  of the investigational drug will be included in the subject’s 
informed consent and should be discussed with the subject as part of the informed consent 
signing and during the study as needed. 
 
7.1.6. 
Relationship of AEs to the Study Drug 
The Investigator will document his/her opinion of the relationship of the AE to treatment with 
the study drug (Table 3). 
Table 3: Relationship of AEs to Study Drug 
 
Relationship 
Description 
Yes 
A reaction that follows a reasonable temporal sequence from administration of the 
drug or in which the drug level has been established in body fluids or tissue; that 
follows a known or expected response pattern to the suspected drug; and that is 
confirmed by improvement on stopping or reducing the dosage of the drug, and 
reappearance of the reaction on repeated exposure. 
No 
An AE will be considered related, unless it f ulfills the criteria specified below: 
Evidence exists that the AE has a cause other than [18F]GTP1 (eg, preexisting 
medical condition, underlying disease, intercurrent illness, or concomitant 
medication). AND/OR The AE does not have a plausible temporal relationship 
with [18F]GTP1 administration. 
 
7.2. 
Serious Adverse Event and Adverse Event of Special Interest 
Reporting 
To ensure subject safety, every SAE and AESI, regardless of suspected causality, occurring after 
the subject has provided informed consent and until the subject has completed the study must be 
reported to the study sponsor within 24 hours of learning of its occurrence. 
SAEs that occur later than the Follow-up Phone Call will not require reporting unless the 
Investigator believes the event(s) were related to either the investigational study drug or study 
procedures. 
Recurrent episodes, complications, or progression of the initial SAE/AESI must be reported as 
follow-up to the original episode, regardless of when the event occurs. This report must be 
submitted within 24 hours of the Investigator receiving the follow-up information. An 
SAE/AESI that is considered completely unrelated to a previously reported one should be 
reported separately as a new event. New signs or symptoms or a change in the diagnosis, 
significant new diagnostic test results, change in the event’s outcome, including recovery, 
additional information on the clinical course of the event should also be submitted immediately. 

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All SAE/AESIs, regardless of causality, will be reviewed by the study sponsor. 
 
7.3. 
Methods for Capturing and Assessing Safety Parameters 
The investigator is responsible for ensuring that all adverse events (see Section 7.1.1for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in accordance 
with instructions provided in this section and in Section 7.2 and 7.4. For each adverse event 
recorded on the Adverse Event eCRF, the investigator will make an assessment of seriousness 
(see Section 7.1.2 for seriousness criteria), severity (see Section 7.1.1), and causality (see Section 
7.1.6). 
 
7.4. 
Procedures for Recording Adverse Events 
 
7.4.1. 
Diagnosis versus Signs and Symptoms 
A diagnosis (if known) should be recorded on the Adverse Event eCRF rather than individual 
signs and symptoms (eg, record only liver failure or hepatitis rather than jaundice, asterixis, and 
elevated transaminases). However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded on the Adverse Event eCRF. If a diagnosis is subsequently 
established, all previously reported adverse events based on signs and symptoms should be 
nullified and replaced by one adverse event report based on the single diagnosis, with a starting 
date that corresponds to the starting date of the first symptom of the eventual diagnosis. 
 
7.4.2. 
Adverse Events That are Secondary to Other Events 
In general, adverse events that are secondary to other events (e.g., cascade events or clinical 
sequelae) should be identified by their primary cause, with the exception of severe or serious 
secondary events. A medically significant secondary adverse event that is separated in time from 
the initiating event should be recorded as an independent event on the Adverse Event eCRF. 
 
7.4.3. 
Deaths 
All deaths that occur during the protocol-specified adverse event reporting period (see Section 
7.2), regardless of relationship to study drug, must be recorded on the Adverse Event eCRF and 
immediately reported. The event or condition that caused or contributed to the fatal outcome 
should be recorded as the single medical concept on the Adverse Event eCRF. 
 
7.5. 
Post-Study Adverse Events: 
If the investigator becomes aware of any serious adverse event that occurs after the end of the 
adverse event reporting period (defined as within 4 days (± 2 days) post-injection of [18F]GTP1), 
if the event is believed to be related to prior study drug treatment. The investigator should report 
these events directly to the Sponsor or its designee, by scanning and emailing the paper Clinical 
Trial Adverse Event/Special Situations Form using the email address provided below: 
Email address: welwyn.pd s-pc@roche.com 

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8. 
DATA REVIEW AND DATABASE MANAGEMENT 
8.1. 
Site Monitoring 
During the study, a contracted clinical research associate (monitor) will visit the site regularly to 
check the completeness of subject records, the accuracy of data, the adherence to the protocol 
and to GCP, the progress of enrollment, and to ensure that study drug is being stored, dispensed, 
and accounted for according to specifications. Key study personnel must be available to assist 
the contracted monitor during these visits. 
The Investigator will maintain source documents for each subject in the study, consisting of case 
and visit notes containing demographic and medical information, laboratory data, ECGs, and the 
results of any other tests or assessments. All information in the database must be traceable to 
these source documents in the subject's file. The Investigator must also keep the original 
informed consent form signed by the subject (a signed copy is given to the subject). 
The Investigator will give the monitor access to all relevant source documents to confirm their 
consistency with the database entries. Monitoring standards require full verification for the 
presence of informed consent, adherence to the inclusion/exclusion criteria, documentation of 
SAEs, and the recording of data that will be used for all primary and safety variables. Additional 
checks of the consistency of the source data with the database are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
subjects will be disclosed. 
 
8.2. 
Database Management and Quality Control 
Designated Investigator staff must enter the information required by the protocol into the study- 
specific database. 
Subsequently, the entered data are systematically checked by Quality Assurance (QA) and data 
management staff, including 100% verification with source documentation. Errors or omissions 
are reconciled with the investigational site for resolution. Quality checking audits of all key 
safety and efficacy data in the database are made prior to locking the database. 
 
9. 
DATA ANALYSIS 
9.1. 
Subject Demographics and Other Baseline Characteristics 
All data for background and demographic variables will be listed. Summary statistics will be 
provided for these parameters by subject. Relevant medical history, current medical conditions, 
results of laboratory screens, drug tests, and any other relevant information will be listed by 
subject. 
 
9.2. 
Imaging Analysis and Statistics 
Whole-body tomographic PET images created on the PET camera will be transferred to a 
dedicated PMOD (software for biomedical image quantification) workstation and reviewed 
visually for assessment of body organ distribution of radioactivity. Manually delineated dynamic 

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VOIs will be placed on the visually identified source organs and subsequently used for all the 
study PET frames. Activity within these VOIs is expressed in unit of total radioactivity. 
Radioactivity will be corrected for body attenuation, but not for decay, and time-activity curves 
(TACs) will be generated for each source organ. Following the last imaging time point residual 
radioactivity will be assumed to undergo physical decay only. Total number of disintegrations 
(ie, kinetic values or residence times) will be determined for each source organ either directly as 
the area under the curve of each TAC, or from modeling of acquired TACs in certain source 
organs (eg, gallbladder emptying, urinary bladder voiding, and GI tract modeling). These data 
will be utilized in the MIRD calculations of target organ specific radiation absorbed dose with 
correction from urine assays and standard GI kinetic models (ICRP 2006) in Organ Level 
Internal Dose Assessment (OLINDA) (Stabin et al., 2005). Standard MIRD assumptions will be 
incorporated in dosimetry models for determination of radiation absorbed doses in target organs 
and whole-body (Harrison et al. 2015, ICRP 2007). 
For whole-body biodistribution, the following parameters will be evaluated: 
● Total source organ counts based on an individualized VOI template 
● Source organ uptake and washout with calculation of the total number of disintegrations (or 
residence time) using the area under the time-activity curve divided by the injected dose of 
radiopharmaceutical 
● Radiation absorbed dose estimates based on the MIRD methodology utilizing urine data in 
the model for increased accuracy of urinary bladder wall dose 
● The ICRP 100 human alimentary tract (HAT) model will be applied to compute residence 
times in the small intestine, lower and upper large intestine 
Descriptive statistics will be applied to describe biodistribution of [18F]GTP1 by organ. 
 
9.3. 
Safety Analysis and Statistics 
Safety will be evaluated by the following: 
● Incidence and severity of AEs 
● Results from measurements of vital signs 
● Results from measurements of ECGs 
● Physical evaluation 
● Results from measurements for parameters of clinical laboratory tests (hematology, clinical 
chemistry, and urinalysis) 
All vital signs, ECG, laboratory and AE data will be listed by subject and visit/time and, if 
ranges are available, abnormalities will be flagged and brought to the Investigator’s attention for 
review. Summary statistics will be provided by visit/time. 

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9.4. 
Sample Size 
The sample size for this study was determined by practical considerations and is not based on 
statistical power calculations. Up to 6 evaluable subjects (with at least 1 male and 1 female) will 
complete this study. 
While the sample size is small, this should be adequate to determine biodistribution and 
dosimetry calculations of [18F]GTP1 in Japanese subjects. 
 
10. 
REGULATORY AND ETHICAL CONSIDERATIONS 
10.1. 
Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH E6Guidelines for GCP, with applicable local regulations, and with the ethical principles laid 
down in the Declaration of Helsinki. 
 
10.2. 
Informed Consent Procedures 
Eligible subjects may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB approved informed consent. Informed consent must be 
obtained before conducting any study-specific procedures (ie, all of the procedures described in 
the protocol). The process of obtaining informed consent should be documented in the subject 
source documents. 
 
10.3. 
Confidentiality 
Participants will be identified by a unique number assigned during screening and participant 
names will be known only to the Investigators and designated study staff. Representatives from 
the FDA will have access to the medical records connected to this study. Study records will be 
kept confidential to the extent provided by law. Name or other identifying data will not be used 
in any report or publication of this study. The data from this study will be maintained for a 
minimum of ten years. 
 
10.4. 
Responsibilities of the Investigator and IRB 
The protocol and the proposed informed consent form must be reviewed and approved by a 
properly constituted IRB before study start. A signed and dated statement that the protocol and 
informed consent have been approved by the IRB must be present before study initiation. Prior to 
study start, the Investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol and to give access to all relevant data and records to the 
contracted monitor, auditors, IRB, and regulatory authorities as required. If an inspection of the 
clinical site is requested by a regulatory authority, the Investigator must inform the study sponsor 
immediately that this request has been made. 

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11. 
REFERENCES 
Arriagada PV, Growdon JH, Hedley-Whyte ET, Hyman BT. 1992. Neurofibrillary tangles but 
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Bohórquez S, Marik J, Ogasawara A, Tinianow JN, Gill HS, Barret O, Tamagnan G, Alagille E, 
Ayalon G, Manser P, Bengtsson T, Ward M, Willaims SP, Kerchner GA, Seibyl JP, Marek K, 
Weimer RM. 2019. [18F]GTP1 (Genentech Probe 1), a radioligand for detecting neurofibrillary 
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Churcher, I. 2006. Tau therapeutic strategies for the treatment of Alzheimer’s disease. Curr Top 
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Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, Pontecorvo MJ, Hefti 
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Cristy M. 1981. Active bone marrow distribution as a function of age in humans. Phys.Med.Biol. 
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Delaere P, Duyckaerts C, Brion JP, Poulain V, Hauw JJ. 1989. Tau, paired helical filaments and 
amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in 
aging and senile dementia of Alzheimer type. Acta Neuropathologica 77:645-53. 
Dickson TC, Saunder HL, Vickers JC. 1997. Relationship between apolipoprotein E and the 
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Duyckaerts C, Brion JP, Hauw JJ, Flament-Durand J. 1987. Quantitative assessment of the 
density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. 
Comparison of immunocytochemistry with a specific antibody and Bodian’s protargol method. 
Acta Neuropathologica 73:167-70. 
Duyckaerts C, Delare P, Hauw JJ, Abbamondi-Pinto AL, Sorbi S, Allen I, et al. 1990. Rating of 
the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A 
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Grundke II, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. 1986. Abnormal 
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Harrison J. 2015. Overview of ICRP Committee 2 'Doses from Radiation Exposure'. Ann.ICRP 
Jun;44(1 Suppl):15-23. 
International Commission on Radiological Protections. 2006. Human alimentary tract model for 
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International Commission on Radiological Protections. 2007. The 2007 Recommendations of the 
International Commission on Radiological Protection. ICRP publication 103. Ann. ICRP;37(2- 
4):1-332. 
Hyman BT, Phelps CH, Beach TG, et al. 2012. National Institute on Aging-Alzheimer’s 
Associated guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers 
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Klunk WE, Engler H, Nordberg A, Wang Y, Blomquist G, Holt DP, et al. 2004a. Imaging brain 
amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306-19. 
Klunk WE, Lopresti BJ, Ikonomovic MD, Lefterov IM, Koldamova RP, Abrahamson EE, et al. 
2004b. Binding of the positron emission tomography tracer Pittsburgh compound-B reflects 
the amount of amyloid beta in Alzheimer’s disease brain but not in transgenic mouse brain. J 
Neurosci 25:10598-606. 
Kosik KS, Joachim CT, Selkoe DJ. 1986. Microtubule-associated protein tau (tau) is a major 
antigenic component of paired helical filaments in Alzheimer’s disease. Proc Natl Acad Sci 
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Leinonen V, Alafuzoff I, Aalto S, Suotunen T, Savolainen S, Nagren K, et al. 2008. Assessment 
of beta-amyloid in a frontocortical brain biopsy specimen and by positron emission 
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McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, et al. 1999. Soluble 
pool of Abeta amyloid determinant of severity of neurodegeneration in Alzheimer’s disease. 
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Ruiqig N, Gilberg PG, Bergfors A, Marutle A, Nordberg A. 2013. Amyloid tracers detect 
multiple binding sites in Alzheimer’s disease brain tissue. Brain 136:2217-2227. 
Sojkova J, Driscoll I, Iacono D, Zhou Y, Codispoti KE, Kraut MA, Ferrucci L, Pletnikova O, 
Mathis CA, Klunk WE, O'Brien RJ, Wong DF, Troncoso JC, Resnick SM. 2011. In vivo 
fibrillar beta-amyloid detected using [11C]PiB positron emission tomography and 
neuropathologic assessment in older adults. Arch Neurol 68(2): 232-40. 
Stephens A, Barthel H, Ishii K, Takao M, Akatsu H, Murayama S, Rowe C, Koglin N, Catafau 
A, Schulz-Schaeffer W, Sabbagh M, Sabri O, Seibyl J. 2014. A negative florbetaben PET scan 
reliably excludes amyloid pathology as confirmed by histopathology. Alzheimer’s & Dementia 
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12. 
APPENDIX 1 – WORLD HEALTH ORGANIZATION TOXICITY GRADING 
SCALE 
WHO Toxicity Grading Scale for determining the severity of AEs 
 
ITEM 
Grade 1 Toxicity 
Grade  2 Toxicity 
Grade 3 Toxicity 
Grade  4 Toxicity 
HEMATOLOGY 
Hemoglobin 
9.5 - 10.5 gm/Dl 
8.0 - 9.4 gm/DI 
6.5 - 7.9 gm/DI 
<6.5 gm/DI 
Absolute Neutrophil 
Count 
1000-1500/mm3
 
750-999/mm 
3
 
500-749/mm3
 
<500/mm3
 
Platelets 
75000-99000/mm3
 
50000-74999/mm3
 
20000-49000/mm3
 
<20000/mm3
 
Prothrombin 
Time (PT) 
1.01 - 1.25 x ULN 
1.26-1.5 x ULN 
1.51 -3.0 x ULN 
>3 x ULN 
Activated Partial 
Thromboplastin 
(APPT) 
1.01 - l.66 x ULN 
1.67 - 2.33 x ULN 
2.34-3 x ULN 
>3 x ULN 
Fibrinogen 
0.75 - 0.99 x LLN 
0.50 - 0.74 x LLN 
0.25 - 0.49 x LLN 
<0.25xLLN 
Fibrin Split Product 
20-40 mcg/ml 
41-50 mcg/ml 
51-60 mcg/ml 
> 60 mcg/ml 
Methemoglobin 
5 -9 .9% 
10.0 - 14.9 % 
15.0- 19.9% 
>20 % 
LIVER ENZYMES 
AST (SGOT) 
l.25-2.5  x ULN 
2.6-5 x ULN 
5.1-10 x ULN 
> l0 x ULN 
ALT (SGPT) 
l.25-2.5  x ULN 
2.6-5 x ULN 
5.1-10 x ULN 
> l0 x ULN 
GGT 
1.25 -2.5 x ULN 
1.6- 5 x ULN 
5.1-10 x ULN 
> l0 x ULN 
Alkaline  Phosphatase 
1.25-2. 5 x ULN 
1.6- 5 x ULN 
5.1-10 x ULN 
> l0 x ULN 
Amylase 
1.1 - 1.5 x ULN 
1.6 - 2.0 x ULN 
2.1-5.0 x ULN 
>5.1 x ULN 
CHEMISTRIES 
Hyponatremia 
130-135 mEq/L 
123-129 mEq/L 
116-122 mEq/L 
< 116 or mental status 
changes or seizures 
Hypernatremia 
146-150 mEq/L 
151-157 mEq/L 
158-165 mEq/L 
> 165 mEq/L or mental 
status changes or 
seizures 
Hypokalemia 
3.0 - 3.4 mEq/L 
2.5 - 2.9 mEq/L 
2.0 - 2.4 mEq/L 
or intensive 
replacement Rx 
required or 
hospitalization 
required. 
<2.0mEq/L 
or paresis or ileus or 
life-threatening 
arrhythmia 
Hyperkalemia 
5.6 - 6.0 mEq/L 
6.1 - 6.5 mEq/L 
6.6 - 7.0 mEq/1 
> 7.0mEq/L 
or life-threatening 
arrhythmia 
Hypoglycemia 
55-64 mg/dL 
40-54 mg/dL 
30-39mg/dL 
<30 mg/dL or mental 
status changes or coma 

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WHO Toxicity Grading Scale for determining the severity of AEs, continued 
 
ITEM 
Grade 1 Toxicity 
Grade  2 Toxicity 
Grade 3 Toxicity 
Grade  4 Toxicity 
CHEMISTRIES  (continued) 
Hyperglycemia 
(note if fasting) 
116 - 160 mg/dL 
161- 250 mg/dL 
251 - 500 mg/dL 
> 500 mg/dL or 
ketoacidosis   or 
seizures 
Hypocalcemia 
(corrected  for albumin) 
8.4 - 7.8 mg/dL 
7.7 - 7.0 mg/dL 
6.9 - 6.1 mg/dL 
< 6.1 mg/dL 
or life-threatening 
arrhythmia  or tetany 
Hypercalcemia 
(correct  for albumin) 
10.6 - 11.5 mg/dL 
11.6 - 12.5 mg/dL 
12.6 - 13.5 mg/dL 
> 13.5 mg/dL  life- 
threatening 
arrhythmia 
Hypomagnesemia 
l.4- l.2mEq/L 
1.1 - 0.9 mEq/L 
0.8 - 0.6 mEq/L 
< 0.6 mEq/L or life- 
threatening 
arrhythmia 
Hypophosphatemia 
2.0 - 2.4 mg/dL 
1.5 -1.9 mg/dL or 
replacement   Rx 
required 
1.0-1.4 mg/dL intensive 
Rx or hospitalization 
required 
< 1.0 mg/dL or life- 
threatening  arrhythmia 
Hyperbilirubinemia 
1.1 -1.5 x ULN 
1.6-2.5 x ULN 
2.6-5 x ULN 
>5 x ULN 
BUN 
l.25-2.5  x ULN 
2.6-5 x ULN 
5.1- l0 x ULN 
> l0 x ULN 
Creatinine 
1.1-l.5 x ULN 
1.6-3.0 x ULN 
3.l-6 x ULN 
> 6 x ULN or required 
dialysis 
URINALYSIS 
Proteinuria 
1+or<  0.3%  or <3g/L 
or 200  mg - 1 gm 
loss/day 
2 -3 + or 0.3 - 1.0% or 
3-10 g/L 
1- 2 gm loss/day 
4+or>  1.0%  or>  10 
g/L 
2-3 5 gm loss/day 
nephrotic syndrome or > 
3 5 gm loss/day 
Hematuria 
microscopic  only 
gross, no clots 
gross+  clots 
obstructive   or required 
transfusion 
CARDIAC  DYSFUNCTION 
Cardiac Rhythm 
asymptomatic, 
transient  signs, no 
Rx required 
recurrent/persist ent; 
No Rx required 
requires  treatment 
Hypertension 
transient  inc. >20mm; 
no Rx 
recurrent,  chronic,  > 
20 mm, Rx required 
requires  acute  Rx; No 
hospitalization 
requires 
hospitalization 
Hypotension 
transient  orthostatic 
hypotension,  No Rx 
symptoms correctable 
with oral  fluids  Rx 
requires  IV fluids; no 
hospitalization 
required 
requires 
hospitalization 
Pericarditis 
minimal  effusion 
mild/moderate 
asymptomatic 
effusion,  no Rx 
symptomatic effusion; 
pain; ECG changes 
tamponade; 
pericardiocentesis   or 
surgery  required 
Hemorrhage,  Blood 
Loss 
microscopic/occult 
mild, no transfusion 
gross  blood loss; 
1-2 units  transfused 
massive blood loss; 
> 3 units  transfused 

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WHO Toxicity Grading Scale for determining the severity of AEs, continued 
 
ITEM 
Grade 1 Toxicity 
Grade  2 Toxicity 
Grade 3 Toxicity 
Grade  4 Toxicity 
RESPIRATORY 
Cough 
transient- no Rx 
treatment  associated 
cough 
local Rx 
uncontrolled 
Bronchospasm,   Acute 
transient;  no Rx 
< 80% - 70% FEV1 
(or peak flow) 
requires  Rx 
normalizes  with 
bronchodilator;  FEV1 
50% - 70% 
(or peak flow) 
no normalization  with 
bronchodilator; 
FEV1  25% - 50% 
(or peak flow 
retractions) 
cyanosis:  FEV1 
< 25% 
(or peak flow) or 
intubated 
GASTROINTES TINAL 
Stomatitis 
mild discomfort;  no 
limits on activity 
some limits on 
eating/drinking 
eating/talking very 
limited 
requires  IV fluids 
Nausea 
mild discomfort; 
maintains reasonable 
intake 
moderate  discomfort; 
intake decreased 
significantly;  some 
activity lin1ited 
severe discomfort;  no 
significant  intake; 
activities  limited 
minimal fluid intake 
Vomiting 
transient  emesis 
occasional/mode  rate 
vomiting 
orthostatic 
hypotension or IV 
fluids required 
hypotensive shock or 
hospitalization  required 
for IV fluid therapy 
Constipation 
Mild 
moderate 
severe 
distensions w/vomiting 
Diarrhea 
transient  3-4 loose 
stools/day 
5-7 loose stools/day 
orthostatic 
hypotension or 
> 7 loose stools/ day 
or required  IV fluids 
hypotensive shock or 
hospitalization for IV 
fluid therapy  required 
NEURO  & NEUROMUS CUL AR 
Neuro-Cerebellar 
slight incoordination 
dysdiadochokinesis 
intention tremor, 
dysmetria,  slurred 
speech;  nystagmus 
locomotor ataxia 
incapacitated 
Mood 
mild anxiety or 
depression 
moderate  anxiety or 
depression  and 
therapy required 
severe anxiety or 
depression  or mania; 
needs  assistance 
acute psychosis; 
incapacitated,  requires 
hospitalization 
Neuro Control (ADL 
activities  of daily 
living) 
mild difficulty 
concentrating;  no Rx; 
mild 
confusion/agitation; 
ADL unaffected 
moderate 
confusion/agitation 
some limitation of 
ADL; minima l Rx 
severe 
confusion/agitation 
needs  assistance for 
ADL; therapy 
required 
toxic psychosis; 
hospitalization 
Muscle  Strength 
subjective weakness 
no objective 
symptoms/signs 
mild objective 
signs/symptoms no 
decrease  in function 
objective weakness 
function limited 
paralysis 

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WHO Toxicity Grading Scale for determining the severity of AEs, continued 
 
ITEM 
Grade 1 Toxicity 
Grade  2 Toxicity 
Grade 3 Toxicity 
Grade  4 Toxicity 
OTHER PARAMETE RS 
FEVER: oral, >12 hours 
37.7-38.5 C or 
100.0-101.5 F 
38.6-39.5 C or 
101.6-102.9 F 
39.6-40.5 C or 
103-105 F 
>40 C or 
>105 F 
Headache 
mild, no Rx therapy 
transient, moderate, Rx 
required 
severe, responds to initial 
narcotic therapy 
intractable; required repeated 
narcotic therapy 
Fatigue 
no decrease in ADL 
normal activity 
decreased 25-50% 
normal activity 
decreased >50% can’t 
work 
unable to care for self 
Allergic Reaction 
pruritus without rash 
localized urticaria 
generalized urticaria; 
angioedema 
anaphylaxis 
Local Reaction 
tenderness or erythema 
induration < 10 cm or 
phlebitis or inflammation 
induration > 10 cm or 
ulceration 
necrosis 
Mucocutaneous 
erythema; pruritus 
diffuse, maculopopular 
rash, dry desquamation 
vesiculation, moist 
desquamation, or 
ulceration 
exfoliative dermatitis, 
mucous membrane 
involvement or erythema, 
multiforme or suspected 
Stevens-Johnson or necrosis 
requiring surgery 

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13. 
APPENDIX 2 – PROTOCOL SUMMARY OF CHANGES, AMENDMENT 1 
 
Rationale: 
Updates were included to clarify that approved forms of birth control are not prohibited 
prescription medications. 
 
The following amendments were incorporated: 
 
Page 
Section 
17-Jan-2020, v1.0 
WAS 
21-Jan-2020, v2.0 
IS 
1 
Title Page, 
Header 
V1.0, 17-Jan-2020 
V2.0, 21-Jan-2020 
9,19 
Synopsis, 
Exclusion 
Criteria 
Use of any prescription drugs, herbal 
supplements, within four weeks prior 
to initial dosing. 
Use of any prescription drugs (except 
approved forms of birth control noted 
in Section 5.2.3), herbal supplements, 
within four weeks prior to initial 
dosing. 
21 
Concomitant 
Treatment 
Use of any prescription drugs, herbal 
supplements, within four (4) weeks 
prior to initial dosing, and/or OTC 
medication, dietary supplements 
(vitamins included) within two (2) 
weeks prior to initial dosing is 
prohibited. If needed (ie, an incidental 
and limited need), acetaminophen is 
acceptable, but must be documented 
as a concomitant 
medication/significant non-drug 
therapy. 
Use of any prescription drugs, herbal 
supplements, within four (4) weeks 
prior to initial dosing, and/or OTC 
medication, dietary supplements 
(vitamins included) within two (2) 
weeks prior to initial dosing is 
prohibited. Approved forms of 
prescription birth control (hormonal 
contraceptives, hormone-releasing 
intrauterine d evices, and copper 
intrauterine d evices) are not 
prohibited and will be d ocumented as 
a concomitant med ication. If needed 
(ie, an incidental and limited need), 
acetaminophen is acceptable, but 
must be documented as a concomitant 
medication/significant non-drug 
therapy. 

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14. 
APPENDIX 3 – PROTOCOL SUMMARY OF CHANGES, AMENDMENT 2 
 
Rationale: 
Updates were included to add information on adverse events of special interest, special situations 
(accidental overdose or medication error), and methods for capturing and assessing safety. 
 
The following amendments were incorporated: 
 
Page 
Section 
21-Jan-2020, v2.0 
WAS 
09-July-2020, v3.0 
IS 
1 
Title Page, 
Header 
V2.0, 21-Jan-2020 
V3.0, 09-Jul-2020 
29 
Section 
7.1.3 
N/A 
Added section to define adverse 
events of special interest. (see 
inserted text below) 
29 
Section 
7.1.4 
N/A 
Added section to define special 
situations, cases of accidental 
overdose or medication error. (see 
inserted text below) 
30 
Section 
7.1.5 
Once an AE is detected, it should be 
followed until its resolution or until it 
is judged to be permanent, and 
assessment should be made at each 
visit (or more frequently, if 
necessary) of any changes in severity, 
the suspected relationship to the study 
drug, the interventions required to 
treat it, and the outcome. 
Information about common side 
effects already known about the 
investigational drug will be included 
in the subject’s informed consent and 
should be discussed with the subject 
during the study as needed. 
Once an AE is detected, it should be 
followed until its resolution to 
baseline grade or better, or until it is 
judged to be stable or permanent by 
the investigator, or the participant 
withd raws consent,. and aAssessment 
should be made at each visit (or more 
frequently, if necessary) of any 
changes in severity, the suspected 
relationship to the study drug, the 
interventions required to treat it, and 
the outcome. 
Information about potential risks 
common sid e effects alread y known 
about of the investigational drug will 
be included in the subject’s informed 
consent and should be discussed with 
the subject as part of the informed 
consent signing and during the study 
as needed. 

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31 
Section 7.2 
7.2 Serious Adverse Event 
Reporting 
To ensure subject safety, every SAE, 
regardless of suspected causality, … 
Recurrent episodes, complications, or 
progression of the initial SAE must be 
reported … An SAE that is 
considered completely unrelated to a 
previously reported one should be 
reported separately as a new event. 
All SAEs, regardless of causality, will 
be reviewed by the study sponsor. 
7.2 Serious Adverse Event and 
Adverse Event of Special Interest 
Reporting 
To ensure subject safety, every SAE 
and AESI, regardless of suspected 
causality, … 
Recurrent episodes, complications, or 
progression of the initial SAE/AESI 
must be reported … An SAE/AESI 
that is considered completely 
unrelated to a previously reported one 
should be reported separately as a 
new event. New signs or symptoms or 
a change in the d iagnosis, significant 
new d iagnostic test results, change in 
 t he event ’s out come, includ ing   
recovery, ad d itional information on 
the clinical course of the event should 
also be submitted immed iately. 
All SAE/AESIs, regardless of 
causality, will be reviewed by the 
study sponsor. 
32 
Section 7.3 
N/A 
Added section to define methods for 
capturing and assessing safety 
parameters. (see inserted text below) 
32 
Section 7.4 
N/A 
Added section to define the 
procedures for adverse event 
reporting. (see inserted text below) 
32 
Section 7.5 
N/A 
Added section to define the 
procedures for post-study adverse 
events. (see inserted text below) 
 
 
 
Sections inserted for Protocol Amendment 2: 
 
Section 7.1.3. - Definition of adverse events of special interest 
Adverse events of special interest (AESI) are required to be reported by the investigator to the 
Sponsor immediately (ie, no more than 24 hours after learning of the event; see Section 7.3 for 
reporting instructions).  AESI for this study are as follows: 

Pr ot oc ol  N o.  G N 4 2 0 4 3  
V 3. 0  ; 0 9 -J ul-2 0 2 0  
C o nfi de ntial  
Pa ge  4 5  of 4 7  
 
•  
Cases  of p ote ntial dr u g-i n d uce d li ver i nj ur y t hat i ncl u de a n ele vate d A L T  or A S T  i n 
c o m bi nati o n wit h  eit her a n ele vate d bilir u bi n  or  cli nical ja u n dice, as defi ne d  b y H y's La w  
•  
T he  fi n di n g of a n ele vate d A L T  or A S T  ( > 3 U L N)  i n c o m bi nati o n wit h  eit her a n ele vate d 
t ot al bilir u bi n   ( 2  U L N)  or cli nical ja u n dice i n t he a bse nce of c h olestasis or ot her ca uses of 
h y per bilir u bi ne mia  is c o nsi dere d t o be a n i n dicat or of se vere li ver i nj ur y (as defi ne d  b y  H y's 
La w).  T heref ore,  i n vesti gat ors m ust  re p ort as a n A E t he occ urre nce  of  eit her of t h e 
f oll o wi n g: 
•  
Treat me nt -e mer ge nt A L T  or A S T  > 3 x  U L N  i n c o m bi nati o n wit h  t ot al bilir u bi n   > 2 x U L N  
•  
Treat me nt -e mer ge nt A L T  or A S T  > 3 x U L N  i n c o m bi nati o n wit h  cli nical ja u n dice 
•  
T he  m ost  a p pr o priate dia g n osis  or (if a dia g n osis  ca n n ot be esta blis he d) t he a b n or mal 
la b orat or y val ues  s h o ul d be rec or de d o n t he A d verse  E ve nt e C R F  a n d re p orte d t o t h e 
S p o ns or  i m me diatel y (ie, n o m ore  t ha n 2 4 h o urs  after  lear ni n g of t h e e ve nt), eit her as a S A E  
or a n A E SI.  
•  
S us pecte d tra ns missi o n  of a n i nfecti o us a ge nt b y t he st u d y dr u g,  as defi ne d bel o w  
•  
A n y  or ga nis m,  vir us,  or i nfecti o us particle  (e g, pri o n  pr otei n  tra ns mitti n g tra ns missi ble 
s p o n gif or m e nce p hal o pat h y),  pat h o ge nic  or n o n -pat h o ge nic,  is c o nsi dere d a n i nfecti o us 
a ge nt.  A tra ns missi o n  of a n i nfecti o us a ge nt ma y  be s us pecte d fr o m cli nical s y m pt o ms or 
la b orat or y fi n di n gs t hat i n dicate a n i nfecti o n i n a s u bject e x p ose d t o a me dici nal  pr o d uct.  
T his  ter m a p plies o nl y  w he n  a c o nta mi nati o n of t he st u d y dr u g  is s us pecte d. 
 
 
Secti o n  7. 1. 4.  - Defi niti o n  of c ases of acci de nt al  o ver d ose  or  me dic ati o n  err or 
Acci de ntal  o ver d ose a n d me dicati o n err or ( hereafter c ollecti vel y referre d t o as "s pecial 
sit uati o ns"), are defi ne d  as f oll o ws: 
•  
Acci de ntal  o ver d ose:  acci de ntal  a d mi nistrati o n of  a dr u g  i n a q ua ntit y t hat is hi g her   t ha n t h e 
assi g ne d d ose  
•  
Me dicati o n  err or:  acci de ntal  de viati o n i n t he a d mi nistrati o n of a dr u g  
o  I n s o me cases, a me dicati o n  err or ma y  be i nterce pte d pri or  t o a d mi nistrati o n of 
t he dr u g.  
S pecial  sit uati o ns are n ot i n t he msel ves A Es  b ut ma y  res ult i n a d verse  e ve nts. Eac h  A E  
ass ociate d wit h  a s pecial sit uati o n s h o ul d be rec or de d se paratel y o n t he A d verse E ve nt e C R F.  If 
t he ass ociate d a d verse  e ve nt f ulfills seri o us ness criteria, t h e e ve nt s h o ul d be re p orte d t o t h e 
S p o ns or  i m me diatel y (ie, n o m ore  t ha n 2 4 h o urs aft er  lear ni n g of t h e e ve nt; see Secti o n  7. 2).  F or  
[1 8F] G T P 1,  a d verse  e ve nts ass ociate d wit h s pecial sit uati o ns s h o ul d be rec or de d as descri be d  
bel o w  f or eac h sit uati o n: 
•  
Acci de ntal  o ver d ose:  E nt er t he a d verse  e ve nt ter m. C hec k t h e " Acci de ntal o ver d ose" a n d 
" Me dicati o n err or" b o xes.  
•  
Me dicati o n  err or t hat d o es  n ot  q ualif y  as a n o ver d ose: E nter  t h e a d verse  e ve nt ter m. C hec k  
t he " Me dicati o n err or" b o x. 

Pr ot oc ol  N o.  G N 4 2 0 4 3  
V 3. 0  ; 0 9 -J ul-2 0 2 0  
C o nfi de ntial  
Pa ge  4 6  of 4 7  
 
•  
Me dicati o n  err or t hat q ualifies  as a n o ver d ose: E nter  t he a d verse e ve nt ter m. C hec k t h e 
" Acci de ntal o ver d ose" a n d " Me dicati o n err or" b o xes.  
I n a d diti o n,  all s pecial sit uati o ns ass ociate d wit h  [1 8F] G T P 1,  re gar dless of  w het her  t he y res ult i n 
a n a d verse  e ve nt, s h o ul d be rec or de d o n t he A d verse  E ve nt  e C R F  as descri be d  bel o w:  
•  
Acci de ntal  o ver d ose: E nter t h e dr u g  na me  a n d "acci de ntal  o ver d ose" as t he e ve nt ter m. 
C hec k t he " Acci de ntal o ver d ose" a n d " Me dicati o n err or" b o xes.  
•  
Me dicati o n  err or t hat d o es  n ot  q ualif y  as a n o ver d ose: E nter  t h e na me  of t h e dr u g  
a d mi nistere d a n d a descri pti o n  of t h e err or (e g, wr o n g d ose  a d mi nistere d, wr o n g d osi n g 
sc he d ule, i nc orrect r o ute of a d mi nistrati o n, wr o n g dr u g,  e x pire d dr u g  a d mi nistere d) as t h e 
e ve nt ter m. C hec k t he " Me dicati o n err or" b o x. 
•  
Me dicati o n  err or t hat q ualifies  as a n o ver d ose: E nter  t he dr u g  na me  a n d "acci de ntal 
o ver d ose" as t he e ve nt ter m. C hec k t h e " Acci de ntal o ver d ose" a n d " Me dicati o n err or" b o xes.  
E nt er  a descri pti o n  of t he err or i n t h e a d diti o nal  case details.  
•  
I nterce pt e d me dicati o n  err or: E nter t h e dr u g  na me  a n d "i nterce pte d me dicati o n  err or" as t he 
e ve nt ter m. C hec k t he " Me dicati o n err or" b o x. E nter  a descri pti o n  of t he err or i n t h e 
a d diti o nal  case details.  
As  a n e xa m ple, a n acci de ntal  o ver d ose t hat res ulte d i n a hea dac he  w o ul d re q uire t w o e ntries o n 
t he A d verse  E ve nt e C R F,  o ne e ntr y t o re p ort t h e acci de ntal  o ver d ose a n d o ne e ntr y t o re p ort t h e 
hea dac he.  T he  " Acci de ntal o ver d ose" a n d " Me dicati o n err or" b o xes  w o ul d nee d t o be c hec ke d 
f or b ot h  e ntries. 
 
Secti o n  7. 3. – Defi niti o n  of met h o ds  f o r c a pt uri n g a n d  assessi n g  s afet y p ar a meters  
T he  i n vesti gat or is res p o nsi ble f or e ns uri n g t hat all a d verse  e ve nts (see Secti o n  7. 1. 1f or  
defi niti o n)  are rec or de d o n t he A d verse  E ve nt  e C R F a n d re p orte d t o t he S p o ns or  i n acc or da nce 
wit h  i nstr ucti o ns pr o vi de d i n t his secti o n a n d i n Secti o n  7. 2 a n d 7. 4. F or eac h a d v ers e  e ve nt 
rec or de d o n t he A d verse  E ve nt e C R F,  t he i n vesti gat or will  ma ke  a n assess me nt  of seri o us ness 
(see Secti o n  7. 1. 2 f or seri o us ness criteria), se verit y (see Secti o n  7. 1. 1),  a n d ca usalit y (see Secti o n  
7. 1. 6).  
 
Secti o n  7. 4. – Defi ni n g  pr oce d ures f o r rec or di n g a d verse  e ve nts 
7. 4. 1.  Di a g n osis  vers us  Si g ns  a n d  S y m pt o ms  
A dia g n osis  (if k n o w n)  s h o ul d be rec or de d o n t h e A d verse  E ve nt e C R F  rat her t ha n i n di vi d ual 
si g ns a n d s y m pt o ms (e g, rec or d o nl y  li ver fail ure or he patitis  rat her t ha n ja u n dice, asteri xis, a n d 
ele vate d tra nsa mi nases).  H o we ver, if a c o nstellati o n of si g ns a n d/ or s y m pt o ms ca n n ot be 
me dicall y  c haracterize d as a si n gle dia g n osis  or s y n dr o me at t h e ti me of re p orti n g, eac h 
i n di vi d ual e ve nt s h o ul d be rec or de d o n t he A d verse  E ve nt  e C R F.  If a dia g n osis  is s u bse q ue ntl y 
esta blis he d, all pre vi o usl y  re p orte d a d verse  e ve nts base d  o n si g ns a n d s y m pt o ms s h o ul d be 
n ullifie d  a n d re place d  b y o ne a d verse e ve nt re p ort base d  o n t he si n gle dia g n osis,  wit h  a starti n g 
d at e  t hat c orres p o n ds t o t h e starti n g d at e  of t he first s y m pt o m of t h e e ve nt ual  dia g n osis.  

Protocol No. GN42043 
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7.4.2. Adverse Events That are Secondary to Other Events 
In general, adverse events that are secondary to other events (e.g., cascade events or clinical 
sequelae) should be identified by their primary cause, with the exception of severe or serious 
secondary events. A medically significant secondary adverse event that is separated in time from 
the initiating event should be recorded as an independent event on the Adverse Event eCRF. 
7.4.3. Deaths 
All deaths that occur during the protocol-specified adverse event reporting period (see Section 
7.2), regardless of relationship to study drug, must be recorded on the Adverse Event eCRF and 
immediately reported. The event or condition that caused or contributed to the fatal outcome 
should be recorded as the single medical concept on the Adverse Event eCRF. 
 
Section 7.5. – Defining procedures for post-study adverse events 
If the investigator becomes aware of any serious adverse event that occurs after the end of the 
adverse event reporting period (defined as within 4 (± 2 days) post-injection of [18F]GTP1), if the 
event is believed to be related to prior study drug treatment. The investigator should report these 
events directly to the Sponsor or its designee, by scanning and emailing the paper Clinical Trial 
Adverse Event/Special Situations Form using the email address provided below: 
Email address: welwyn.pds-pc@roche.com