Clinical trial NCT04564092
Conditions: Healthy Subjects (HS)
Keywords: Single photon emission computed tomography (SPECT) Healthy Volunteer (HV)
Sponsor: GE Healthcare
Start date: 2021-05-13; Completion date: 2021-09-04
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase 1, single-centre, single-group, nonrandomized, noncomparative, open-label, single-dose study to evaluate the safety, biodistribution, internal radiation dosimetry, and effective dose of DaTSCAN™ ioflupane (123I) injection in Chinese Healthy Volunteers.

Detailed description:

Arms: arm 1: Participants will receive a single intravenous (IV) injection of DaTSCAN™ ioflupane (123I) injection into an arm vein, followed by planar whole-body imaging at prespecified time points over a period of 48 hours after administration. Brain SPECT imaging will be acquired at 3 and 6 hours after administration.
Interventions: intervention 1: DaTSCAN™ Ioflupane (123I) Injection
Intervention descriptions: intervention 1: Each participant will receive a single administration of DaTSCAN™ ioflupane (123I) injection by bolus IV injection with a nominal iodine (123I) activity of 111 MBq ±10%, in a maximum volume of 5 mL.

Protocol documents:
Prot_SAP_000.pdf: 
GE Confidential 
Page 1 of 58 
Clinical Study Protocol 
GE Healthcare 
GE-001-023 
Title: A phase 1, nonrandomised, noncomparative, open-label study to assess the safety, 
biodistribution, and internal radiation dosimetry of a single dose of DaTSCAN™ ioflupane 
(123I) injection in Chinese healthy volunteers 
REVISED TO INCORPORATE AMENDMENT A02 
Sponsor 
GE Healthcare Ltd. and its Affiliates (hereinafter referred to as the “sponsor”) 
Pollards Wood 
Nightingales Lane 
Chalfont St Giles 
HP8 4SP 
United Kingdom  
Medical Director 
Quan Hu, MD, PhD 
GE Healthcare 
1 Hua Tuo Rd 
Zhangjiang Hi-Tech Park 
Pudong 
Shanghai 
201203 
P.R. China 
Tel: + 86 21 38774044 
E-Mail: quan.hu@ge.com 
Confidentiality Statement 
This protocol is provided for conducting a clinical research study. The information contained in 
this document is confidential and, except to the extent necessary to obtain informed consent or 
IEC/IRB approval, cannot be disclosed unless required by governmental regulation. Persons to 
whom any portion of the contents of this document is disclosed must be informed that the 
information is confidential and may not be further disclosed by them. 
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Investigator’s Signature Page 
I have read this protocol and all associated case report forms and agree to conduct this study in 
full accordance with the stipulations of the protocol described herein. 
 
 
 
Signature 
 
 
 
Date 
Print Name 
 
 
 
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1 
SYNOPSIS 
Name of Sponsor/Company: 
GE Healthcare Ltd. and its 
Affiliates 
Individual Study Table 
Referring to Part of Dossier in 
Which the Individual Study or 
Study Table is Presented: 
 
Volume: 
 
Reference: 
 
(For National Authority Use 
Only) 
 
Name of Finished Product: 
DaTSCAN™ 
Name of Active Ingredient: 
Ioflupane (123I) 
Title of Study: A phase 1, nonrandomised, noncomparative, open-label study to assess the safety, 
biodistribution, and internal radiation dosimetry of a single dose of DaTSCAN™ ioflupane (123I) injection in 
Chinese healthy volunteers. 
Protocol Number: GE-001-023 
Investigators and Study Centre: This study will be conducted in a single study centre in the People's 
Republic of China  
Phase of Development: Phase 1 
Objectives:  
Primary Objective: 
 
To evaluate the safety of a single dose of ioflupane (123I) injection in Chinese healthy volunteers (HVs) 
Secondary Objectives: 
 
To determine the biodistribution, internal radiation dosimetry, and effective dose (ED) of ioflupane (123I) 
injection after intravenous (IV) administration in Chinese HVs. 
 
To compare biodistribution and dosimetry findings in this Chinese group with those previously established 
in European HVs. 
 
To compare brain single photon emission computed tomography (SPECT) imaging results in this Chinese 
group with those previously established in European HVs. 
Study Design:  
This is a phase 1, single-centre, single-group, nonrandomised, noncomparative, open-label, single-dose study to 
evaluate the safety, biodistribution, internal radiation dosimetry, and ED of DaTSCAN™ ioflupane (123I) 
injection in Chinese HVs. Eight evaluable subjects (4 males and 4 females) will be included in the study.  
The study will consist of a minimum of 3 visits for each subject. Each subject will attend a screening visit 
within 20 days before injection, an imaging visit, and a follow-up visit approximately 2 weeks after injection. 
During the screening visit, the subjects must satisfy all entry criteria and undergo safety assessments.  
During the imaging visit, each subject will receive by bolus IV administration, a single dose of ioflupane (123I) 
injection with a nominal 123I activity of 111 MBq ± 10% and will undergo simultaneous whole-body (head to 
mid-thigh) anterior and posterior planar scintigraphy scans at 10 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 24 
hours, and 48 hours after administration. Brain SPECT imaging will be performed at 3 and 6 hours after 
administration. A reference source will be imaged alongside the subject. Time-activity curves will then be 
generated from 123I activity data from all 8 subjects and integrated to obtain the normalised-cumulated activity 
in each source region, which will then be used along with the Medical Internal Radiation Dosimetry (MIRD) 
schema to determine the internal radiation dosimetry. The dosimetry will be evaluated for the Cristy-Eckerman 
female and hermaphrodite male phantoms.  
For evaluation of the biodistribution and radiation dosimetry, blood (up to 5 mL) samples will be collected at 1 
hour before administration of ioflupane (123I) injection and at the following times after administration: 5, 15, 30 
minutes and 1, 2, 3, 4, 5, 24, and 48 hours. Urine excreted from 1 hour before administration of ioflupane (123I) 
injection to 48 hours after administration will be collected as voided. 
At the follow-up visit, all subjects will undergo specified safety assessments, and all female subjects of 
childbearing potential will also have a urine pregnancy test. 
All subjects’ safety will be monitored during the course of the study. The safety analysis will include the 
following: 
 
Adverse events (AEs) up to study exit. 
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Name of Sponsor/Company: 
GE Healthcare Ltd. and its 
Affiliates 
Individual Study Table 
Referring to Part of Dossier in 
Which the Individual Study or 
Study Table is Presented: 
 
Volume: 
 
Reference: 
 
(For National Authority Use 
Only) 
 
Name of Finished Product: 
DaTSCAN™ 
Name of Active Ingredient: 
Ioflupane (123I) 
 
A tolerability questionnaire to be completed at approximately 1 hour before injection and at approximately 
15 minutes, 1, 4, 24, 48 hours after injection. 
 
Physical examination at prespecified time points. 
 
Clinical laboratory tests (serum biochemistry, haematology, and urinalysis) at screening visit (which will 
be considered baseline), and at approximately 3 hours, 48 hours, and 2 weeks after injection.  
 
Injection site monitoring (at baseline, at approximately 1 hour before injection, and at approximately 4 
hours after injection). 
 
Vital signs and oxygen saturation (at screening visit; at baseline; at approximately 1 hour before injection; 
and at approximately 10, 20, and 30 minutes; approximately 1, 2, 4, 24, and 48 hours; and approximately 2 
weeks after injection).  
 
12-lead electrocardiogram (ECG) (at screening visit, at approximately 1 hour before injection, and at 
approximately 2 and 5 hours after injection).  
 
Concomitant medications. 
Selection of Subjects: 
Inclusion Criteria: 
To be included in this study, a subject will have to meet all of the following criteria: 
(1) 
Chinese male or female who has agreed to sign and date the written informed consent form 
(2) 
Age 18-70 years  
(3) 
Body mass index (BMI) of 18-30 kg/m2  
(4) 
General good state of health as judged by a qualified physician after completing physical examination 
(5) 
Fit, co-operative, and able to provide consent 
 
Exclusion Criteria: 
Subjects are to be excluded from this study if they meet any of the following criteria: 
(1) 
Sensitivity to DaTSCAN™ ioflupane (123I) injection or any of its ingredients 
(2) 
A history of motor disturbances 
(3) 
A history of pulmonary, cardiovascular, neurological, renal or hepatic, hormonal or coagulation disorders 
or hyperthyroidism 
(4) 
A history of drug, alcohol, or solvent abuse 
(5) 
The subject has been previously enrolled in this study or participated in a clinical study involving an 
investigational pharmaceutical product within 30 days prior to screening 
(6) 
Radionuclide injection within a minimum of 5 radioactive half-lives prior to screening 
(7) 
Use of any medication (except paracetamol [acetaminophen] or oral contraceptive), including traditional 
Chinese medicine, within 2 weeks prior to the imaging visit 
(8) 
Classification as a radiation worker 
(9) 
Women of child-bearing potential not accepting a highly effective method of birth control (A woman is 
considered of child-bearing potential, i.e., fertile, following menarche and until becoming post-
menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral 
salpingectomy and bilateral oophorectomy. Postmenopausal is defined as 12 months with no menses 
without an alternative medical cause, in International Council on Harmonisation (ICH) M3 (R2); A highly 
effective method of birth control is defined as one which results in a low failure rate (i.e., less than 1 % 
per year) when used consistently and correctly, such as implants, injectables, combined oral 
contraceptives, some intrauterine devices, sexual abstinence or vasectomised partner, in ICH M3 (R2).) 
(10) Pregnant or lactating women 
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Name of Sponsor/Company: 
GE Healthcare Ltd. and its 
Affiliates 
Individual Study Table 
Referring to Part of Dossier in 
Which the Individual Study or 
Study Table is Presented: 
 
Volume: 
 
Reference: 
 
(For National Authority Use 
Only) 
 
Name of Finished Product: 
DaTSCAN™ 
Name of Active Ingredient: 
Ioflupane (123I) 
Number of Subjects/Centres Planned: A total of 8 adult HVs (4 males and 4 females) at 1 centre 
Treatment of Subjects: 
 
Investigational Medicinal Product (IMP): Each subject will receive a single administration of ioflupane 
(123I) injection by bolus IV injection contralaterally to the sampling catheter. The nominal activity of 123I 
should be 111 MBq ±10%, in a maximum volume of 5 mL. 
 
Standard of Truth: None. 
 
Duration of Treatment: The administration of ioflupane (123I) injection will last for 15 to 20 seconds via 
injection into an arm vein, followed by whole body imaging, brain SPECT imaging, etc. The duration of 
the imaging visit will last approximately 48 hours after injection of IMP.  
Safety and Biodistribution/Dosimetry Variables: 
Safety Variables: 
Primary Outcome Measures:  
Safety variables will include monitoring of the following:  
 
Occurrence of AEs up to study exit  
 
Results of a tolerability questionnaire to be completed at prespecified time points 
 
Results of physical examinations at prespecified time points 
 
Results of clinical laboratory tests at prespecified time points  
 
Results of injection site monitoring at prespecified time points 
 
Results of vital signs (blood pressure, heart rate, body temperature, respiratory rate) and oxygen saturation 
at prespecified time points 
 
Results of ECG examinations at prespecified time points  
Secondary Outcome Measures: Dosimetry estimates and cumulated activity by source region and by entire 
body (including whole blood, plasma, and excreted urine) at time points up to 48 hours after administration in 
HVs. 
Biodistribution/Dosimetry: 
Biodistribution data in HVs will consist of 123I activity in organs and tissues of interest at multiple time points, 
123I activity in whole blood and plasma at multiple time points, and 123I activity in voided urine. The 123I activity 
in voided urine will be calculated as the product of the 123I activity measured in each void multiplied by the 
volume of that void. The absorbed doses of radiation to organs and tissues will be evaluated for the Cristy-
Eckerman female and hermaphrodite male phantoms. Descriptive statistics of absorbed doses to the target 
organs and tissues specified in the MIRD schema will be tabulated. 
Imaging Variables: 
Planar whole-body scanning will be performed serially at prespecified time points over a period of 
approximately 48 hours after administration (n=8 HVs). Brain SPECT imaging will be acquired at 3 and 6 
hours after administration (n=8 HVs). 
Statistical Methods and Planned Analysis: 
Tabulations of summary statistics, graphical presentations, and statistical analyses will be performed with 
SAS® software. No confirmatory hypothesis testing is intended to be performed. P-values will be interpreted as 
a metric of uncertainty. All data will be listed by subject number and time point (if applicable). Confidence 
intervals, both individual and simultaneous, will be at the 95% confidence level unless otherwise noted. The 
last pre-administration observation will be used as the baseline value for calculating post-administration 
changes from baseline. Demographic and other baseline information will be summarised.   
An overall summary of AEs will be presented, and they will be coded with Medical Dictionary for Regulatory 
Activities (MedDRA) and summarised by MedDRA system organ class and preferred term. Results of the 
following evaluations performed before and after DaTSCAN™ administration will be summarised with 
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Name of Sponsor/Company: 
GE Healthcare Ltd. and its 
Affiliates 
Individual Study Table 
Referring to Part of Dossier in 
Which the Individual Study or 
Study Table is Presented: 
 
Volume: 
 
Reference: 
 
(For National Authority Use 
Only) 
 
Name of Finished Product: 
DaTSCAN™ 
Name of Active Ingredient: 
Ioflupane (123I) 
observed values and changes from baseline: physical examinations, 12-lead ECGs, vital signs (blood pressure, 
heart rate, respiratory rate, and body temperature) and oxygen saturation, injection site monitoring, and clinical 
laboratory evaluations (haematology, serum biochemistry, and urinalysis). Concomitant medications will be 
summarised. In addition, results of the tolerability questionnaire given after DaTSCAN™ administration will 
be summarised in descriptive statistics and boxplot. 
Dosimetry estimates (using MIRD methods) and cumulated activity by source region and by entire body 
(including whole blood, plasma, and excreted urine) at time points up to 48 hours after administration will be 
summarised. The ED as calculated by using International Commission on Radiological Protection (ICRP) 
methods will be summarised. In addition, the following measures will be compared between the Chinese 
subjects from this study and European subjects: the normalised cumulative activity, absorbed doses, and ED. 
These measures will be compared by using the 2-sample t-test.  
Striatal binding ratios (SBR) will be analysed to determine the stability of striatal uptake relative to a reference 
region over the proposed imaging window of 3 to 6 hours after administration. The difference between the SBR 
at 3 and 6 hours calculated for each subject will be tested by Wilcoxon signed-rank test. 
Sample Size Estimates: No sample size calculations were performed. The sample size has been chosen to 
fulfil local regulatory requirements. 
 
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2 
TABLE OF CONTENTS 
2.1 
Overall Table of Contents 
Page Number 
1 
SYNOPSIS ..................................................................................................................... 3 
2 
TABLE OF CONTENTS ............................................................................................... 7 
2.1 
Overall Table of Contents .................................................................................. 7 
2.2 
List of Tables ...................................................................................................... 9 
2.3 
List of Figures ..................................................................................................... 9 
3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................. 10 
4 
BACKGROUND INFORMATION ............................................................................. 11 
5 
STUDY OBJECTIVES AND PURPOSE .................................................................... 12 
6 
STUDY DESIGN ......................................................................................................... 13 
6.1 
Overall Study Design and Plan ......................................................................... 13 
6.2 
Study Rationale ................................................................................................ 15 
6.3 
Study Timeframe .............................................................................................. 16 
6.4 
Risks and Benefits to Subjects.......................................................................... 16 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS................................................ 18 
7.1 
Procedures for Enrolment ................................................................................. 18 
7.2 
Inclusion Criteria .............................................................................................. 18 
7.3 
Exclusion Criteria ............................................................................................. 18 
7.4 
Withdrawal and Termination Criteria............................................................... 19 
8 
TREATMENT OF SUBJECTS .................................................................................... 21 
8.1 
Investigational Medicinal Product .................................................................... 21 
8.2 
Method of Numbering Subjects and Assigning Subjects to Treatment Groups23 
8.3 
Selection of Doses and Timing ......................................................................... 23 
8.4 
Blinding ............................................................................................................ 23 
8.5 
Concomitant Medications ................................................................................. 23 
8.6 
Treatment Compliance ..................................................................................... 23 
9 
STUDY PROCEDURES .............................................................................................. 24 
9.1 
Screening Visit ................................................................................................. 27 
9.2 
Imaging Visit .................................................................................................... 27 
9.3 
Follow-up Visit ................................................................................................. 29 
10 
OUTCOME MEASURES ............................................................................................ 30 
10.1 
Primary Outcome Measures (Safety Variables) ............................................... 30 
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10.2 
Secondary Outcome Measures ......................................................................... 38 
10.3 
Other Variables ................................................................................................. 40 
11 
DATA HANDLING AND QUALITY ASSURANCE ................................................ 41 
11.1 
Completing and Signing Case Report Forms ................................................... 41 
11.2 
Clinical Data Management ............................................................................... 41 
11.3 
Archiving .......................................................................................................... 41 
12 
STATISTICAL METHODS AND PLANNED ANALYSIS ...................................... 42 
12.1 
General Statistical Considerations .................................................................... 42 
12.2 
Populations for Analysis ................................................................................... 42 
12.3 
Subject Demographics/Other Baseline Characteristics .................................... 42 
12.4 
Study Treatments .............................................................................................. 43 
12.5 
Primary Analysis (Safety) ................................................................................ 43 
12.6 
Secondary Analysis .......................................................................................... 45 
12.7 
Interim Analysis ............................................................................................... 46 
12.8 
Sample Size Calculation ................................................................................... 47 
12.9 
Power for Analysis of Critical Secondary Variables ........................................ 47 
12.10 Procedures for Missing, Unused and Spurious Data ........................................ 47 
12.11 Rules for Excluding Subjects from Analysis .................................................... 47 
12.12 Procedures for Reporting Deviations from Original Statistical Plan ............... 47 
13 
SPECIAL REQUIREMENTS AND PROCEDURES ................................................. 48 
13.1 
Regulatory, Institutional and Ethical Review ................................................... 48 
13.2 
Investigator’s Responsibilities .......................................................................... 48 
13.3 
Protocol Deviations .......................................................................................... 49 
13.4 
Study Monitoring .............................................................................................. 49 
13.5 
Audit and Inspection ......................................................................................... 49 
13.6 
Insurance ........................................................................................................... 50 
13.7 
Publication Policy ............................................................................................. 50 
14 
REFERENCES ............................................................................................................. 51 
15 
APPENDICES .............................................................................................................. 52 
15.1 
Information on Investigational and Registered Products ................................. 52 
15.2 
Equipment Parameters ...................................................................................... 52 
15.3 
Normal Limits for Vital Signs, Oxygen Saturation and ECG Intervals ........... 52 
15.4 
Tolerability Questionnaire ................................................................................ 53 
16 
CLINICAL PROTOCOL AMENDMENT SUMMARIES .......................................... 56 
16.1 
Amendment A01 .............................................................................................. 56 
16.2 
Amendment A02 .............................................................................................. 57 
 
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2.2 
List of Tables 
Table 1 
Study Schedule of Events ......................................................................................... 25 
Table 2 
Clinical Laboratory Parameters ................................................................................ 31 
Table 3 
Criteria for Normal Limits for Vital Signs and Oxygen Saturation ......................... 52 
Table 4 
Criteria for Normal Limits for ECGs ....................................................................... 53 
 
2.3 
List of Figures 
Figure 1 
Study Diagram .......................................................................................................... 14 
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3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
BMI 
Body mass index 
CRF 
Case report form 
CRO 
Contract research organisation 
DAT 
Dopaminergic transporter protein 
ECG 
Electrocardiogram 
ED 
Effective dose 
EDC 
Electronic data capture 
GCP 
Good Clinical Practice 
β-hCG 
Beta-human chorionic gonadotropin 
HV 
Healthy volunteer 
IB 
Investigator Brochure 
ICH 
International Council on Harmonisation 
ICRP 
International Commission on Radiological Protection 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IRB 
Institutional/Independent Review Board 
IV 
Intravenous 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIRD 
Medical internal radiation dose 
PS 
Parkinsonian syndromes 
ROI 
Region of interest 
SAE 
Serious adverse event 
SBR 
Striatal binding ratios 
SOP 
Standard operating procedure 
SPECT 
Single photon emission computed tomography 
TEAE 
Treatment-emergent adverse event 
VAS 
Visual analogue scales 
WBC 
White blood cell 
 
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4 
BACKGROUND INFORMATION 
DaTSCAN™ ioflupane (123I) injection—marketed as DaTscan™ (Ioflupane I 123 injection) in 
the United States—is a radiopharmaceutical for diagnostic use only. The active substance in 
DaTSCAN™ is ioflupane (123I), which binds with high affinity to the presynaptic 
dopaminergic transporter protein (DAT, also known as the dopamine reuptake site).  
DaTSCAN™ is approved in Europe, the United States, Hong Kong and Canada for detecting 
loss of functional dopaminergic neuron terminals in the striatum of patients with clinically 
uncertain Parkinsonian syndromes (PS), including Parkinson's disease, multiple system 
atrophy, and progressive supranuclear palsy. DaTSCAN™ is useful for differentiating PS from 
essential tremor.  
In Europe, Singapore, Japan, and Mexico, DaTSCAN™ is also approved for use in adult 
patients to help differentiate probable dementia with Lewy bodies from Alzheimer’s disease. 
DaTSCAN™ is unable to discriminate between dementia with Lewy bodies and Parkinson’s 
disease dementia. 
The current phase 1 study is intended to determine the safety, biodistribution, internal radiation 
dosimetry, and effective dose (ED) of DaTSCAN™ ioflupane (123I) injection after intravenous 
(IV) administration in Chinese healthy volunteers (HVs). The results of this study will be 
compared with corresponding findings from the study of European HVs. The results of this 
study will be incorporated into a submission to regulatory authorities in the People's Republic 
of China.  
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5 
STUDY OBJECTIVES AND PURPOSE 
The primary and secondary objectives of the study are as follows: 
Primary Objective 
 To evaluate the safety of a single dose of ioflupane (123I) injection in Chinese HVs. 
Secondary Objectives 
 To determine the biodistribution, internal radiation dosimetry, and ED of ioflupane (123I) 
injection after IV administration in Chinese HVs. 
 To compare biodistribution and dosimetry findings in this Chinese group with those 
previously established in European HVs. 
 To compare brain single photon emission computed tomography (SPECT) imaging results 
in this Chinese group with those previously established in European HVs. 
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6 
STUDY DESIGN 
6.1 
Overall Study Design and Plan 
This is a phase 1, single-centre, single-group, nonrandomised, noncomparative, open-label, 
single-dose study to evaluate the safety, biodistribution, internal radiation dosimetry, and ED 
of DaTSCAN™ ioflupane (123I) injection in Chinese HVs. Eight evaluable subjects (4 males 
and 4 females) will be included in the study. The study will be conducted at a single centre in 
the People's Republic of China. 
The study will consist of a minimum of 3 visits for each subject. Each subject will attend a 
screening visit within 20 days before injection, an imaging visit, and a follow-up visit 
approximately 2 weeks after injection. During the screening visit, the subjects must satisfy all 
entry criteria and undergo safety assessments.  
During the imaging visit, each subject will receive, by bolus IV administration, a single dose of 
ioflupane (123I) injection with a nominal iodine (123I) activity of 111 MBq ± 10% and will 
undergo simultaneous whole-body (head to mid-thigh) anterior and posterior planar 
scintigraphy scans at 10 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 24 hours, and 48 hours after 
administration. Brain SPECT imaging will be performed at 3 and 6 hours after administration. 
A reference source will be imaged alongside the subject. Time-activity curves will then be 
generated from 123I activity data from all 8 subjects and integrated to obtain the normalised-
cumulated activity in each source region, which will then be used along with the Medical 
Internal Radiation Dosimetry (MIRD) schema to determine the internal radiation dosimetry. 
The dosimetry will be evaluated for the Cristy-Eckerman female and hermaphrodite male 
phantoms. 
For evaluation of the biodistribution and radiation dosimetry, blood (up to 5 mL) samples will 
be collected at 1 hour before administration of ioflupane (123I) injection and at the following 
times after administration of IMP: 5, 15, 30 minutes and 1, 2, 3, 4, 5, 24, and 48 hours. Urine 
excreted from 1 hour before administration of ioflupane (123I) injection to 48 hours after 
administration will be collected as voided. 
At the follow-up visit, all subjects will undergo specified safety assessments, and all female 
subjects of childbearing potential will also have a urine pregnancy test. 
All subjects’ safety will be monitored during the course of the study. The safety analysis will 
include the following:  
 AEs up to study exit.  
 A tolerability questionnaire to be completed at approximately 1 hour before injection and at 
approximately 15 minutes, 1, 4, 24, 48 hours after injection. 
 Physical examination at prespecified time points. 
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 Clinical laboratory tests (serum biochemistry, haematology, and urinalysis) at screening 
visit (which will be considered baseline), and at approximately 3 hours, 48 hours, and 2 
weeks after injection. 
 Injection site monitoring (at baseline, at approximately 1 hour before injection, and at 
approximately 4 hours after injection). 
 Vital signs and oxygen saturation (at screening visit; at baseline; at approximately 1 hour 
before injection; and at approximately 10, 20, and 30 minutes; approximately 1, 2, 4, 24, 
and 48 hours; and approximately 2 weeks after injection). 
 12-lead electrocardiogram (ECG) (at screening visit, at approximately 1 hour before 
injection, and at approximately 2 and 5 hours after injection).  
 Concomitant medications. 
An overview of study procedures is presented in Figure 1. 
Figure 1 Study Diagram 
 
Screening Visit 
 
Informed consent 
 
Inclusion/exclusion criteria 
 
Demographic information 
 
Medical/surgical history 
 
Concomitant medications 
 
Safety assessments (physical examination, vital signs and oxygen saturation, clinical laboratory 
tests, ECG, AEs) 
 
Pregnancy test (for women of child-bearing potential) 
  
 
Within 20 days after 
screening visit; 
subjects will remain 
at the centre for 
approximately 48 
hours after IMP 
injection 
DaTSCAN™ Imaging Visit 
 
Confirm inclusion/exclusion criteria 
 
Concomitant medications 
 
Pregnancy test (for women of child-bearing potential) 
 
Thyroid blocking (pre- and post-injection) 
 
Safety assessments (pre- and post-injection: physical examination, vital signs and oxygen 
saturation, clinical laboratory tests, ECG, injection site monitoring, AEs) 
 
Administration of IMP 
 
Simultaneous whole body (head to mid-thigh) anterior and posterior planar scintigraphy scans 
at approximately 10 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 24 hours, and 48 hours after 
administration (a reference source will be imaged along with subject) 
 
Brain SPECT imaging at 3 and 6 hours after administration 
 
Blood sampling at approximately 1 hour before injection; approximately 5 minutes, 15 minutes, 
30 minutes, and 1, 2, 3, 4, 5, 24, 48 hours after injection 
 
Urine collection from approximately 1 hour before injection to 48 hours after injection 
 
Tolerability questionnaire (1 hour before injection and 15 minutes, and 1, 4, 24, and 48 hours 
after injection) 
 
 
Two weeks after 
IMP injection 
Follow-up Visit 
 
Concomitant medications 
 
Safety assessments (physical examination, vital signs and oxygen saturation, clinical laboratory 
tests, AEs) 
 
Pregnancy test (for women of child-bearing potential) 
 
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6.2 
Study Rationale 
The quantity of ioflupane in the 5 mL formulation of DaTSCAN™ ioflupane (123I) injection is 
0.625 µg. The pharmacokinetics of DaTSCAN™ ioflupane (123I) injection has been studied in 
healthy adults. Because administration is IV, absorption is complete and ioflupane (123I) is 
completely bioavailable.  
The pharmacokinetics of DaTSCAN™ ioflupane (123I) injection were studied by monitoring 
radioactivity after IV injection. Similar studies have already been done to evaluate the 
pharmacokinetics of DaTSCAN™ ioflupane (123I) injection in European subjects [Study CY 
95.FP.1], [Frear 1998] and Japanese subjects (Study NMA98P1 [Takano et al 1999]). The 
current study will involve Chinese subjects. 
In this study, anterior and posterior whole-body images will be obtained by using a 2-headed 
gamma camera at 10 minutes, 1 hour, 2 hours, 4 hours, 5 hours, 24 hours, and 48 hours after 
injection of DaTSCAN™. A dual-head scintillation camera, medium-energy collimator, and 
standard imaging techniques will be used. An external 123I calibration source will be imaged 
alongside the subject. 
Biodistribution of 123I after administration of DaTSCAN™ will be measured by whole-body 
imaging in conjunction with serial blood and urine sampling. From regions of interest (ROIs) 
placed upon conjugate anterior and posterior whole-body images, the activities in the brain, 
striatum, thyroid, lungs, liver, spleen, stomach, heart, and intestines will be determined. The 
data will be used to calculate initial organ uptake, normalised cumulative activity, absorbed 
organ dose and the ED, according to the methodology of MIRD [Siegal et al 1999] and the 
International Commission on Radiological Protection (ICRP) [ICRP 1991]. 
6.2.1 
Rationale for Administered Radioactivity 
It is planned that the administered radioactivity will be 111 MBq ± 10%. This is less than the 
111 to 185 MBq recommended for clinical DaTSCAN™ SPECT but is sufficient, according to 
previous experience, for planar imaging to determine biodistribution and dosimetry while 
minimising radiation exposure to HVs. 
6.2.2 
Rationale for Safety Monitoring Plan 
Safety assessments will be performed at screening, before and after administration of IMP, and 
approximately 2 weeks after administration of IMP. The planned safety assessments are 
designed to ensure subject safety and to identify and minimise unnecessary risks.  
This study’s safety monitoring plan is justifiable and adequate from a safety standpoint in view 
of the following: 
 The design of the safety plan permits a comparison of the safety variables at baseline (in 
this study baseline period is defined as “after the screening visit up to 1 hour prior to 
administration” except clinical laboratory tests, of which baseline value is that taken during 
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screening visit) and after IV injection of DaTSCAN™ ioflupane (123I) injection in the same 
subject. 
 Safety variables collected in the present study can be compared with safety variables from 
other related studies. 
 The 2-week safety monitoring permits the evaluation of late-appearing adverse events 
(AEs) that may emerge or progress after the administration of DaTSCAN™ ioflupane (123I) 
injection. 
 Evaluation of the safety database held by the sponsor (which includes clinical study data as 
well as post marketing data in the United States and Europe) does not show any new safety 
signals that would require a modification of the safety assessments as planned. 
 The measures used to assess safety are well defined and reliable, and the proposed safety 
analyses are adequate to assess the effects of the administration of ioflupane (123I) injection 
in HVs. 
6.3 
Study Timeframe 
The study is expected to begin enrolment in 2020. The start of the study is defined as the point 
at which all necessary regulatory and local approvals are in place, the study centre staff have 
been adequately trained, and the study centre has sufficient resources available to start 
enrolling subjects. The end of the study is defined as the date of last subject last visit. 
Each subject's participation will consist of 3 study visits. The screening visit may take place up 
to 20 days before IMP injection. The imaging visit will last approximately 48 hours, followed 
by a follow-up visit approximately 2 weeks after IMP injection. 
6.4 
Risks and Benefits to Subjects 
As is true for many phase 1 studies, there are no expected direct benefits to HVs who will be 
subjects in this trial. However, data collected from study participants may help others 
(especially patients) prospectively by contributing to a knowledge base for further evaluation 
of the use of DaTSCAN™ ioflupane (123I) injection. 
The risks to subjects mainly relate to the IV injection and the radiation emitted by the drug. 
From previous experience, IV injection is known to carry a small risk of infection and 
haematoma. This risk is not related to the IMP but to the procedure itself. IV lines will be 
placed and monitored by qualified personnel in order to minimise risk to the subjects.   
DaTSCAN™ is a radiopharmaceutical. As such, it exposes the recipient to ionising radiation. 
However, previous studies have shown that the effective radiation dose is 21 to 24 µSv/MBq, 
so the dose for this procedure is approximately 2.7 mSv, which is slightly over the published 
annual ED equivalent from natural radiation in China [Ziquiang et al 1994]. As the product is a 
radiopharmaceutical intended for diagnostic use, evaluation of dosimetry estimates is 
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mandatory for a marketing authorisation. Therefore, administration of a radioactive dose is 
unavoidable. However, the dose chosen for this study is based on previous experience to ensure 
that useful images can be obtained while minimising the radiation exposure to the HV. 
Administration of a radioactive dose that would not yield useful evaluable images would be 
unethical.  
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7 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1 
Procedures for Enrolment 
The subjects will be recruited by means accepted by the respective regulatory bodies/local 
health authority (in accordance with local regulations) and the local Independent Ethics 
Committee (IEC). 
A maximum of 8 evaluable subjects (HVs) will be enrolled. A written and dated informed 
consent form will be obtained from all subjects prior to any protocol specific procedures being 
performed. 
Each potential subject will attend the clinical site for a screening visit within 20 days before 
IMP administration to ensure that they fulfil the study entry criteria.  Each subject will be given 
a unique identification number. The identification number will be assigned to the subject 
during the screening visit, after the informed consent document has been signed and dated. 
Once an identification number has been assigned, it cannot be reassigned, even if the subject is 
deemed ineligible or withdraws consent. No subject may enter the study more than once. 
Subjects withdrawing before IMP administration (i.e., a non-evaluable subject) will be 
replaced. Additional subjects may be enrolled to reach the required number of evaluable 
subjects within each step (see Section 6.1). Replacement subjects will be assigned unique 
subject numbers. 
7.2 
Inclusion Criteria 
To be included in this study, a subject will have to meet all of the following criteria: 
(1) 
Chinese male or female who has agreed to sign and date the written informed consent 
form 
(2) 
Age 18-70 years 
(3) 
Body mass index (BMI) of 18-30 kg/m2  
(4) 
General good state of health as judged by a qualified physician after completing 
physical examination 
(5) 
Fit, co-operative, and able to provide consent 
7.3 
Exclusion Criteria 
Subjects are to be excluded from this study if they meet any of the following criteria: 
(1) 
Sensitivity to DaTSCAN™ ioflupane (123I) injection or any of its ingredients 
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(2) 
A history of motor disturbances 
(3) 
A history of pulmonary, cardiovascular, neurological, renal or hepatic, hormonal or 
coagulation disorders or hyperthyroidism 
(4) 
A history of drug, alcohol, or solvent abuse 
(5) 
The subject has been previously enrolled in this study or participated in a clinical study 
involving an investigational pharmaceutical product within 30 days prior to screening 
(6) 
Radionuclide injection within a minimum of 5 radioactive half-lives prior to screening 
(7) 
Use of any medication (except paracetamol [acetaminophen] or oral contraceptive), 
including traditional Chinese medicine, within 2 weeks prior to the imaging visit 
(8) 
Classification as a radiation worker 
(9) 
Women of child-bearing potential not accepting a highly effective method of birth 
control (A woman is considered of child-bearing potential, i.e., fertile, following 
menarche and until becoming post-menopausal unless permanently sterile. Permanent 
sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral 
oophorectomy. Postmenopausal is defined as 12 months with no menses without an 
alternative medical cause, in International Council on Harmonisation (ICH) M3 (R2); A 
highly effective method of birth control is defined as one which results in a low failure 
rate (i.e., less than 1 % per year) when used consistently and correctly, such as 
implants, injectables, combined oral contraceptives, some intrauterine devices, sexual 
abstinence or vasectomised partner, in ICH M3 (R2).) 
(10) 
Pregnant or lactating women 
7.4 
Withdrawal and Termination Criteria 
7.4.1 
Subject Withdrawal 
There are no formal withdrawal criteria for this study. During the conduct of the study, the 
sponsor or its designee will review the safety data for trends and signals that would indicate the 
need for withdrawal of a subject. 
In accordance with the Declaration of Helsinki, each subject is free to withdraw from the study 
at any time. Investigator(s) also have the right to withdraw subjects from the study in the event 
of illness, AEs, or other reasons concerning the health or well-being of the subject, or in the 
case of lack of co-operation. 
Should a subject decide to withdraw after administration of the IMP, or should the 
investigator(s) decide to withdraw the subject, all efforts will be made to complete and report 
the observations up to the time of withdrawal as thoroughly as possible. A complete final 
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evaluation at the time of the subject’s withdrawal should be made and an explanation given of 
why the subject is withdrawing or being withdrawn from the study. 
The reason for withdrawal must be noted in the Case Report Form (CRF). If the reason for 
withdrawal is an AE, the specific event or test result(s) must be recorded in the CRF.  If the 
subject discontinues for a serious AE (SAE), such as hospitalization, the subject data will be 
collected and monitored until the outcome is evident.  If the event has ended, the stop date of 
the event will be recorded in the CRF. If the event is still ongoing, the outcome of the event 
must be Ongoing or Not Yet Resolved.  An outcome of Unknown is not acceptable, even if the 
event is ongoing on the date of study discontinuation. 
Subjects who withdraw from the study before the study procedures are complete will be 
replaced. 
7.4.2 
Study or Site Termination 
The sponsor reserves the right to terminate the study at any time. 
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8 
TREATMENT OF SUBJECTS 
8.1 
Investigational Medicinal Product 
8.1.1 
DaTSCAN™ Ioflupane (123I) Injection 
DaTSCAN™ ioflupane (123I) injection is a clear, colourless ethanolic solution for IV injection. 
It is provided in a 5-mL vial for our study.  
The active ingredient in DaTSCAN™ ioflupane (123I) injection is ioflupane (123I). The 5.0 mL 
vial contains 370 MBq at reference time in 5.0 mL of solution. The radionuclidic purity 
is >99%. The radiochemical purity is ≥96% [123I]ioflupane at release, ≥94% [123I]ioflupane at 
expiry; ≤4% [123I]iodide at release, ≤6% [123I]iodide at expiry. The expiry time is 20 hours 
after the activity reference time stated on the label for the 5.0-mL presentation. Inactive 
ingredients include nonradioactive ioflupane (0.1 µg/mL), acetic acid (5.5 mg/mL), sodium 
acetate (7.8 mg/mL), ethanol (5% v/v), water for injection, to 5 mL. 
Like other radiopharmaceuticals, DaTSCAN™ ioflupane (123I) injection should be used only 
by qualified personnel with the appropriate government authorisation for the use and 
manipulation of radionuclides within a designated clinical setting. Appropriate radiation 
precautions should be observed during the preparation and storage of the agent. The product 
should be stored at room temperature and should never be frozen. 
Handling of the material and spill clean-up and disposal will be performed in accordance with 
local regulations and local practice in the nuclear medicine department.  
In this study, each subject will receive 1 dose of DaTSCAN™ ioflupane (123I) injection. Each 
subject will receive a dose of 111 MBq ± 10%, in a maximum volume of 5 mL. To minimise 
pain upon injection, the dose will be delivered by a slow IV injection (not less than 15 to 20 
seconds) into an arm vein. 
8.1.2 
Supply and Packaging 
DaTSCAN™ ioflupane (123I) injection is provided in a properly labelled, single-use 5-mL vial. 
8.1.3 
Stability and Storage 
The IMP should be stored at room temperature (<25°C, no freezing). During both storage and 
dose preparation, appropriate radiation precautions should be observed. 
8.1.4 
Comparator 
No comparator is to be used in this study. 
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8.1.5 
Thyroid Blocking 
To minimise thyroid uptake of radioactive iodine, subjects must undergo appropriate thyroid 
blocking, according to local practice, prior to and after administration of the IMP. For example, 
potassium iodide tablet (approximately 120 mg) or potassium iodide oral solution/Lugol’s 
solution (equivalent to 100 mg iodide) or potassium perchlorate (400 mg) may be used for 
blockade of the thyroid gland, to be administered within 1 to 4 hours prior to and 12 to 24 
hours after injection of DaTSCAN™. 
The thyroid blocking agent will be preferably sourced locally by the hospital. If it is not 
available in the hospital, then sponsor/contract research organisation (CRO) should provide it. 
The administered time, date and dose will be captured on the concomitant medication page of 
CRF. 
8.1.6 
IMP Accountability 
Each investigator is responsible for ensuring that deliveries of IMP(s) and other study materials 
from the sponsor are correctly received, recorded, handled, and stored safely and properly in 
accordance with all applicable regulatory guidelines, and used in accordance with this protocol. 
All IMP containers (opened, unopened, or empty) must be destroyed on site after IMP 
administration for each subject; the site has the option to use external destruction services if 
preferred. The overall drug accountability must be completed by the sponsor or representative. 
A list of IMP(s) and other materials that were destroyed, must be prepared and signed by the 
principal investigator or designee. If there are any discrepancies, an explanation for these 
should also be provided. 
The current Investigator’s Brochure for the IMP will be supplied to the site. 
8.1.7 
Registration of Investigational Medicinal Product Complaints 
In the event of an IMP complaint (e.g., breakage, leakage, particulate matter, discoloration), the 
investigator or recipient of the IMP is requested to report the problem on the IMP shipping 
documentation (e.g., ‘Delivery Note for Product’, Drug Shipping and Receiving Form, or 
equivalent form). This report should be promptly forwarded to the person indicated on the 
shipping documentation. Once the report is received, the Clinical Supplies Manager will 
register the complaint and determine if the complaint is minor or significant, according to 
sponsor procedures. All complaints will be followed up, and the appropriate action will be 
implemented according to sponsor procedures. 
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8.2 
Method of Numbering Subjects and Assigning Subjects to 
Treatment Groups 
This is an open-label noncomparative study. Thus, there will be no randomisation or 
assignment to treatment groups. However, all subjects will be assigned a unique study number 
to protect their privacy.  
8.3 
Selection of Doses and Timing 
In this study, each of the subjects will receive 1 dose of DaTSCAN™ ioflupane (123I) injection. 
The subjects will receive a dose at the lower end of the approved dose range in Europe and the 
United States. The dose in this study will be 111 MBq ± 10%, in a maximum volume of 5 mL.  
This dose was used in the phase 1 study (CY95.FP.I) conducted in Europe. 
The dose is to be delivered by slow bolus (15 to 20 seconds) IV injection; aseptic technique 
will be used during the administration. 
8.4 
Blinding 
This is an open-label study. Therefore, there will be no blinding. 
8.5 
Concomitant Medications 
Individuals who have taken any medication other than paracetamol (acetaminophen) or oral 
contraceptives within 2 weeks prior to the imaging visit are excluded from the study. Subjects 
will receive thyroid blocking agent according to local practice before and after administration 
of DaTSCAN™ ioflupane (123I) injection (Section 8.1.5).  
Any medications taken by the subject from screening  to the end of follow-up visit will be 
recorded in the CRF along with the indication and dosage. Either the generic or the trade name 
may be recorded. The sponsor/CRO will encode all therapy and medication according to a 
current well-recognised dictionary of medical codes. 
8.6 
Treatment Compliance 
The IMP will be administered by study personnel. Each administration volume and the total 
radioactivity injected will be checked and the vial code, dose, and volume per administration 
will be recorded in each subject’s CRF. A dose administered outside of specific dose 
requirements or defined range must be reported as protocol deviations (see Section 13.3). 
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9 
STUDY PROCEDURES 
All measurements obtained during the course of the study are summarised in the Study 
Schedule of Events (Table 1). 
 
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Table 1 
Study Schedule of Events 
Variables 
 
Screening 
Visit (≤20 
days 
before 
IMP) 
Imaging Visit 
Follow-
up Visit 
(2 weeks 
±2 days) 
Before IMP 
Administration IMP 
After IMP Administration 
Baseline 
(to –1 h) 
-1 h 
(±10 
min) 
0 
5 min  
(±2 
min) 
10 min 
(±5 
min) 
15 min 
(±2 
min) 
20 min 
(±5 
min) 
30 min 
(±5 
min) 
1 h 
(±10 
min) 
2 h 
(±10 
min) 
3 h 
(±10 
min) 
4 h 
(±10 
min) 
5 h 
(±10 
min) 
6 h 
(±10 
min) 
24 h 
(±2 
h) 
48 h  
(± 3 
h) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Entry criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic 
information 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/surgical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical laboratory 
tests 
X 
 
 
 
 
 
 
 
 
 
 
Xa 
 
 
 
 
X 
X 
Concomitant 
medications 
 
Pregnancy test (for 
women of child-
bearing potential) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Physical examination 
X 
X 
 
 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
X 
Vital signs and 
oxygen saturation 
X 
X 
X 
 
 
X 
 
X 
X 
X 
X 
 
X 
 
 
X 
X 
X 
12-lead ECG 
X 
 
Xb 
 
 
 
 
 
 
 
Xb 
 
 
Xb 
 
 
 
 
Thyroid blocking 
 
Xf 
 
 
Xf 
 
Injection site 
monitoring 
 
X 
X 
 
 
 
 
 
 
 
 
 
Xb 
 
 
 
 
 
DaTSCAN™ injection 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Planar Image 
acquisition 
 
 
 
 
 
Xc 
 
 
 
X 
X 
 
Xd 
Xd 
 
X 
X 
 
Brain SPECT imaging 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
Blood sampling 
(biodistribution/ 
radiation dosimetry) 
 
 
X 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
 
Tolerability 
questionnaire 
 
 
X 
 
 
 
Xe 
 
 
X 
 
 
X 
 
 
X 
X 
 
AE monitoring 
All AEs and serious AEs (SAEs) will be recorded 
Urine collection 
 
 
Each urine voided approximately 1 hour before IMP administration to 48 hours after IMP administration will be collected 
 
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Table 1 
Study Schedule of Events 
Variables 
 
Screening 
Visit (≤20 
days 
before 
IMP) 
Imaging Visit 
Follow-
up Visit 
(2 weeks 
±2 days) 
Before IMP 
Administration IMP 
After IMP Administration 
Baseline 
(to –1 h) 
-1 h 
(±10 
min) 
0 
5 min  
(±2 
min) 
10 min 
(±5 
min) 
15 min 
(±2 
min) 
20 min 
(±5 
min) 
30 min 
(±5 
min) 
1 h 
(±10 
min) 
2 h 
(±10 
min) 
3 h 
(±10 
min) 
4 h 
(±10 
min) 
5 h 
(±10 
min) 
6 h 
(±10 
min) 
24 h 
(±2 
h) 
48 h  
(± 3 
h) 
AE = adverse event; ECG = electrocardiogram; h = hours; min = minutes; shaded areas indicate continuous measurement or monitoring 
a Time point window is ±1 hour. 
b Time point window is ±30 minutes. 
c Time point window is ±10 minutes. 
d Time point window is ±20 minutes. 
e Time point window is ±5 minutes. 
f  The dosage and timing of administration will be based on investigator’s discretion according to local practice of the study centre (Section 8.1.5). 
 
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9.1 
Screening Visit 
The screening visit must take place within 20 days before IMP injection. At the screening visit, 
demographic information and concomitant medications will be recorded; clinical laboratory 
tests, vital signs and oxygen saturation, and a complete medical and surgical history will be 
taken; and a physical examination, including 12-lead ECG, will be performed. For women of 
child-bearing potential, a serum beta-human chorionic gonadotropin (β-hCG) test for 
pregnancy will be performed.  
To be eligible for this study, subjects must satisfy all entry criteria (fulfil all of the inclusion 
criteria listed in Section 7.2 and none of the exclusion criteria listed in Section 7.3). A signed 
and dated informed consent form must be obtained from all subjects prior to their entering the 
study. 
Waivers or protocol exceptions will not be granted prospectively by the sponsor under any 
circumstances. Any exceptions to protocol-specified requirements will be considered to be 
protocol deviations. 
AE will be monitored after signed and dated informed consent is obtained. 
9.2 
Imaging Visit 
The imaging visit must start within 20 days after the screening visit. This visit will last 
approximately 48 hours. 
9.2.1 
Before IMP Administration 
During the baseline period (defined as “after the screening visit up to 1 hour prior to 
administration”), the following will be recorded/conducted: 
 Confirm inclusion/exclusion criteria 
 Concomitant medications recording 
 Physical examination and injection site monitoring 
 Vital signs and oxygen saturation 
 Thyroid blocking (see Section 8.1.5) 
 Urine β-hCG test for pregnancy (for women of child-bearing potential) 
 AE monitoring 
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Subjects will avoid all food and drink (except water) for 2 hours before and 2.5 hours after 
injection of DaTSCAN™. Then, light meals and unlimited decaffeinated/noncarbonated drinks 
are permitted out to 6 hours after injection. After that, there are no food restrictions, but 
caffeinated/carbonated drinks are limited to 4 cups per 24-hour period. 
For subject comfort and prior to IMP administration, subjects will be advised to empty their 
bladder, and if necessary, have a bowel movement prior to positioning on the scanner and the 
initial scan commencing. 
For women of child-bearing potential, the urine β-hCG test for pregnancy will be performed. 
These subjects cannot participate in the study until the result of the urine β-hCG test is found to 
be negative. 
At approximately 1 hour before injection of IMP, 12-lead ECG, and vital signs and oxygen 
saturation will be recorded, and a tolerability questionnaire filled out. Collection of urine will 
begin. A blood sample for biodistribution and radiation dosimetry will be collected. Two 
cannulas (or indwelling catheters) will be placed, one is in left/right arm/antecubital vein for 
blood sampling, the other is in contralateral side for IMP administration. The injection site will 
be examined for any abnormal findings prior to IMP administration. 
9.2.2 
IMP Administration 
The IMP will be administered by bolus IV injection, injected slowly (15 to 20 seconds) into an 
arm vein under aseptic technique, contralaterally to the sampling catheter. 
9.2.3 
After IMP Administration 
The following will be performed after IMP administration:  
 12-lead ECG will be performed at 2 hours (± 30 minutes) and 5 hours (± 30 minutes) after 
IMP administration. 
 Blood (up to 5 mL) samples for biodistribution and radiation dosimetry will be collected at 
5 minutes (± 2 minutes), 15 minutes (± 2 minutes), and 30 minutes (± 5 minutes) and at 1 
hour (±10 minutes), 2 hours (± 10 minutes), 3 hours (± 10 minutes), 4 hours (± 10 
minutes), 5 hours (± 10 minutes), 24 hours (± 2 hours), and 48 hours (± 3 hours) after IMP 
administration. 
 Each urine excreted from approximately 1 hour before ioflupane (123I) injection to 48 hours 
after ioflupane (123I) injection will be collected as voided.  
 Subjects will undergo simultaneous whole body (head to mid-thigh) anterior and posterior 
planar scintigraphy scans at 10 minutes (+ 10 minutes), 1 hour (± 10 minutes), 2 hours (± 
10 minutes), 4 hours (± 20 minutes), 5 hours (± 20 minutes), 24 hours (± 2 hours), and 48 
hours (± 3 hours) after IMP administration. A reference source will be imaged alongside 
the subject.  
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 Brain SPECT imaging will be performed at 3 hours (± 10 minutes) and 6 hours (± 10 
minutes) after IMP administration.  
 Physical examination and injection site monitoring will be performed at 4 hours (± 30 
minutes) after IMP administration. 
 Clinical laboratory test (blood and urine) samples will be obtained at 3 hours (±1 hour) and 
48 hours (±3 hours) after IMP administration.   
 Vital signs and oxygen saturation will be recorded at 10 minutes (± 5 minutes), 20 minutes 
(± 5 minutes), and 30 minutes (± 5 minutes) and at 1 hour (± 10 minutes), 2 hours (± 10 
minutes), 4 hours (± 10 minutes), 24 hours (± 2 hours), and 48 hours (± 3 hours) hours after 
IMP administration. 
 A tolerability questionnaire will be completed at 15 minutes (± 5 minutes) and 1 hour (± 10 
minutes), 4 hour (± 10 minutes), 24 hours (± 2 hours), and 48 hours (± 3 hours) after IMP 
administration. 
 Thyroid blocking (see Section 8.1.5) 
 AE monitoring. 
 Concomitant medications recording 
See Study Schedule of Events (Table 1) for further details.  Full details of the image protocol 
are presented in the GE-001-023 Imaging Manual. 
9.3 
Follow-up Visit 
The follow-up visit will be conducted 2 weeks (± 2 days) after IMP administration. The 
following will be performed during this visit: 
 Concomitant medications recording 
 Physical examination 
 Vital signs and oxygen saturation 
 Clinical laboratory test (blood and urine) 
 Urine β-hCG test for pregnancy (for women of child-bearing potential) 
 AE monitoring 
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10 
OUTCOME MEASURES 
10.1 
Primary Outcome Measures (Safety Variables) 
The primary objective of this study is to evaluate the safety of a single dose of ioflupane (123I) 
injection in Chinese HVs.  
Safety variables will include monitoring of the following: 
 Occurrence of AEs up to study exit 
 Results of a tolerability questionnaire to be completed at prespecified time points 
 Results of physical examinations at prespecified time points 
 Results of clinical laboratory tests at prespecified time points 
 Results of injection site monitoring at prespecified time points 
 Results of vital signs (blood pressure, heart rate, body temperature, respiratory rate) and 
oxygen saturation at prespecified time points 
 Results of ECG examinations at prespecified time points 
Prespecified normal limits for vital signs, oxygen saturation and ECG intervals are provided in 
Section 15.3.  
10.1.1 
Clinical Laboratory Evaluation 
Clinical laboratory parameters assessed in this study are displayed in Table 2. 
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Table 2 
Clinical Laboratory Parameters 
Serum Biochemistry 
Haematology 
Urinalysis 
Alanine aminotransferase (ALAT) 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase (ASAT) 
Bicarbonate 
Bilirubin (total, direct, indirect) 
Calcium 
Chloride 
Creatine phosphokinase (total) (CPK) 
Creatinine 
Gamma-glutamyltransferase (G-GT) 
Glucose 
Lactate dehydrogenase 
Phosphorous 
Potassium 
Protein (total) 
Sodium 
Urea nitrogen 
Uric acid 
Thyroid function (at screening and 48 
hours after IMP administration) 
C-reactive protein 
Haematocrit  
Haemoglobin  
Red blood cell count 
White blood cell count  
Platelet count  
Prothrombin time (PT)  
Activated partial thromboplastin time (APTT) 
Thrombin time (TT) 
Fibrinogen (FIB) 
Bilirubin 
Glucose 
Ketone 
Occult blood 
pH 
Protein 
Specific gravity 
Urobilinogen 
 
 
The signed and interpreted laboratory results will be kept together with the subject’s CRF as 
supplemental pages, both centrally and at the site. 
All blood samples will be processed and handled per standard laboratory procedures. All 
retained samples will be destroyed according to local practice at site. 
Urine will be collected from approximately 1 hour before IMP administration to 48 hours after 
IMP administration, as described in Table 1. The time of void will be documented on the CRF. 
Urinalysis will be performed as described in Table 2. Urine voided will also be analysed for 
radioactivity. 
Any abnormal laboratory findings that constitute an AE (e.g., any abnormal findings leading to 
an intervention other than repeating the laboratory test) should be reported as such and should 
be followed up until the outcome is known.  
Additional diagnostic tests may be indicated to determine a more precise diagnosis of the 
subject’s condition (e.g., ordering a white blood cell [WBC] differential to help characterise a 
high or low WBC count, or ordering a determination of red cell indices to help characterise a 
low haematocrit).  
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10.1.2 
Vital Signs and Oxygen Saturation 
Vital signs (blood pressure, heart rate, respiratory rate, and body temperature) and oxygen 
saturation will be monitored before and after administration of IMP, according to the Study 
Schedule of Events, Table 1. Before vital signs and oxygen saturation are measured, the subject 
should rest for at least 5 minutes (if possible). The same position will be used each time vital 
signs and oxygen saturation are measured for a given subject.  
10.1.3 
Electrocardiograms 
A standard 12-lead ECG will be performed at the various pre- and post-injection time points 
described in Table 1. All ECG recordings will be read at the investigational site. 
Each 12-lead ECG examination will be evaluated by a licensed physician. A physician reading 
ECGs may make clinical management decisions as needed. 
Reference range limits for 12-lead ECG intervals are provided in Section 15.3. Each 12-lead 
ECG tracing must be signed and dated.  
Interpretation and follow-up of interval data outside of reference ranges and abnormal 
waveforms should be conducted in conjunction with the clinical situation of the subject. 
Each 12-lead ECG examination result at each time point (all intervals, heart rate and 
interpretation, and identified with the subject’s initials, subject’s study number, and date and 
time of recording), will be retained in the investigator’s study record for each subject. The 
investigator will not be expected to calculate QTc intervals.  
10.1.4 
Physical Examination 
A qualified physician will conduct physical examinations at the time points indicated in Table 
1. Where possible the same individual should conduct the physical examination at all required 
time points. The physical examination will include recording an assessment for the presence of 
abnormalities of the following: general appearance, skin, lungs, cardiovascular system, back 
and spine, abdomen, extremities, lymph nodes, and neurological exam. 
In the event that new abnormal physical findings and worsening abnormal physical findings are 
encountered during the study, these terms are defined as follows: a new abnormal physical 
finding is defined as one that occurs when a subject’s normal baseline physical examination 
becomes abnormal post baseline. A worsening abnormal physical finding is defined as one that 
occurs when a subject's abnormal baseline physical examination becomes worse post baseline. 
10.1.5 
Injection Site Monitoring 
The injection site will be monitored at the times indicated in the Study Schedule of Events 
(Table 1). 
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Abnormal injection-site findings include, but are not limited to, radiopharmaceutical 
extravasation, bleeding, haematoma, redness, and infection. Abnormal injection site findings 
will be recorded as AEs in the CRF. 
10.1.6 
Tolerability Questionnaire Interview 
Each subject is required to complete a tolerability questionnaire (see Appendix 15.4) at 
approximately 1 hour before injection and at approximately 15 minutes and 1, 4, 24, 48 hours 
after injection. The questionnaire evaluates subject mood, pain at injection site, itchiness of 
injection site, loss of function at injection site and quality of sleep using 100 mm visual 
analogue scales (VAS)* anchored by the following descriptors: 
Mood 
Bad – 0mm 
Good – 100mm 
Pain at Injection Site 
Normal – 0mm 
Painful – 100mm 
Itchiness of Injection Site 
Normal – 0mm 
Itchy – 100mm 
Loss of Function at Injection Site 
Normal – 0mm 
Loss of Function – 100mm 
Quality of Sleep 
Bad – 0mm 
Good – 100mm 
*Visual Analog Scale (VAS) is a continuous scale comprised of a horizontal line, usually 10 centimetres (100 mm) in length, 
anchored by 2 verbal descriptors: “0” stands for normal, and 100 mm stands for each symptom extreme, or “0” stands for bad, 
and 100 mm stands for good. 
10.1.7 
Adverse Events 
All AEs/SAEs that occur after informed consent shall be recorded in the AE/SAE report form 
(see the Study Schedule of Events, Table 1). 
Study personnel must remain vigilant for the occurrence of AEs, particularly those that may be 
life threatening. Personnel who are trained in the acute management of anaphylaxis and other 
emergencies and who have access to appropriate clinical supplies must be immediately 
available for no less than 60 minutes to observe for possible anaphylactoid reactions after 
dosing. Treatment of SAEs should be primarily supportive of vital functions. 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject which does not necessarily have to have a causal relationship with the IMP.  AEs will 
be asked for from time of informed consent through the follow up visit at 2 weeks (± 2 days) 
after IMP administration.   
A treatment-emergent AE (TEAE) is any unfavourable and unintended sign, symptom, or 
disease temporally associated with the use of DaTSCAN™, whether or not considered related 
to that product.  Only symptoms/signs that begin or worsen in severity and/or frequency after 
DaTSCAN™-administration/use will be recorded as TEAEs in the CRF.   
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The subjects will be closely observed and questioned for any kind of AE during the study 
procedures and at follow-up appointments throughout the study period with non-leading 
questioning (e.g., “How do you feel?”).  The subjects will be instructed to immediately report 
any symptoms and signs to the study staff. 
Both the investigator(s) and sponsor/CRO will perform a causality assessment on any AE, to 
assess whether or not there is a reasonable possibility (evidence to suggest) that the IMP 
caused the event.  
Causal relationship 
Both the investigator(s) and sponsor/CRO will perform a causality assessment on any AE, to 
assess whether or not there is a reasonable possibility (evidence to suggest) that the IMP 
caused the event. 
The relationship of an AE with DaTSCAN™ will be assessed and reported by the investigator 
as: 
 
Reasonably related to study drug (“Reasonable cause”): - A causal relationship between 
DaTSCAN™ and an AE is at least a reasonable possibility, i.e., the relationship cannot 
be ruled out. 
 
Not reasonably related to study drug (“Not reasonable cause”): - A causal relationship 
between DaTSCAN™ and an AE is not a reasonable possibility. 
Expectedness 
All DaTSCAN™-emergent AEs will be assessed, by the sponsor (or CRO on behalf of the 
sponsor), as to whether they were expected to occur or unexpected, meaning not anticipated 
based on current knowledge found in the applicable safety information included in the 
reference safety information in the Investigator Brochure (IB) for DaTSCAN™. 
Unexpected: An unexpected DaTSCAN™-emergent AE is a reaction, for which the nature, 
seriousness, severity or outcome is not consistent with the applicable safety 
information included in the IB. 
Expected: 
An expected DaTSCAN™-emergent AE is a reaction which is consistent with 
the applicable safety information included in the IB. 
Adverse Reaction: An AE that is caused by the IMP. 
Suspected Adverse Reaction: A suspected adverse reaction is an AE where reasonable 
possibility exists for causality between DaTSCAN™ and the AE. 
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10.1.8 
Serious Adverse Events 
An SAE is defined as any AE that: 
 Results in death. 
 Is life threatening. 
 Requires inpatient hospitalisation or prolongation of existing hospitalisation. 
 Results in persistent or significant disability or incapacity. 
 Is a congenital anomaly or birth defect. 
 Is another important medical event.* 
(*Other important medical events are those that may not result in death, be life threatening, or 
require hospitalisation, but may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardise the subject and may require medical intervention to prevent one 
of the outcomes listed above.) 
10.1.9 
Other Significant Adverse Events 
Clinically notable results from vital signs, clinical laboratory, and injection site findings should 
be reported as AEs, where applicable. 
10.1.10 
Adverse Event and Serious Adverse Event Reporting 
All AEs should be recorded by using acceptable diagnoses, if possible. If an AE has already 
been reported, it is not necessary to report each individual sign and symptom of that AE as a 
separate AE. For example, if myocardial infarction is reported as an AE, there is no need to 
report elevated creatine kinase and abnormal ECG or other related signs, symptoms, or 
laboratory values as separate AEs. However, if both occurred in isolation and myocardial 
infarction was not diagnosed, then each event would be reported as an AE. 
The intensity of all AEs will be graded as mild, moderate, or severe by using the following 
definitions: 
Mild: 
Tolerable. 
Moderate: 
Interferes with normal activity. 
Severe: 
Incapacitating (causes inability to perform usual activity or work). 
The investigator will be instructed to closely monitor each subject who experiences an AE 
(whether ascribed to the IMP or not) until the outcome of the AE has been determined. 
In addition to the investigator’s own description of the AEs, each AE will be encoded by the 
sponsor/CRO according to a well-recognised dictionary of medical codes. 
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SAEs will be recorded in the CRF if they occur as follows: 
 
After a subject first signed informed consent and throughout the subject’s follow-up 
period*, whether or not considered related to the IMP, and 
 
After the subject’s follow-up period, and for which a causal relationship to the IMP 
cannot be ruled out. 
(*Follow-up period is defined as the protocol-stipulated period or, for subjects prematurely 
withdrawn from a study, the duration of a subject’s participation.) 
All serious and non-serious AEs must be followed for a final outcome until the end of the 
follow-up period. An outcome of “unknown” is not considered to be an acceptable final 
outcome. An outcome of “not yet resolved” is an acceptable final outcome for non-serious AEs 
at the end of a subject’s participation in a study, and for SAEs at database lock. 
The investigator will report all SAEs to local authorities, sponsor, and IECs/ 
Institutional/Independent Review Boards (IRBs) as required by local regulations, sponsor 
standard operating procedures (SOPs), and site-specific IECs/IRBs. The CRO (on behalf of the 
sponsor) will report all SAEs to local health authorities, IECs/IRBs and investigators as 
required by local regulations and sponsor/CRO SOPs.  
Study centres are instructed to report all SAEs (including DaTSCAN™-emergent SAEs), 
together with a causality assessment, to the sponsor (or a service provider/CRO acting on 
behalf of the sponsor) within 24 hours.  
All AEs and SAEs are reported in the AE form of the CRF. Detailed information about 
management of AE information will be provided, e.g., in a Safety Management Plan or 
equivalent document. 
SAE information will be captured in electronic data capture (EDC).  If the EDC system is 
unavailable, the Investigators must complete an SAE form in English and forward it by fax to 
PPD Pharmacovigilance via at SAE Fax: +44 1223 374 102, immediately (within 24 hours) of 
becoming aware of the event.   
Refer to the current SAE Form and Guidelines for completing and submitting the SAE form. 
Requests for additional information will be made via the CRO personnel at the site.  
Suspected unexpected serious adverse (drug) reactions will be reported to regulatory 
authorities, investigators, and IECs/IRBs in accordance with applicable legal requirements and 
applicable sponsor SOPs. 
10.1.11 
Urgent Safety Measures 
In accordance with the principles of Good Clinical Practice (GCP) as laid out in ICH E6, the 
investigator(s) has/have primary responsibility for assuring subject safety throughout the 
performance of study procedures. An urgent safety measure is defined as any measure which 
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an investigator may need to implement which is a deviation from, or a change in, the protocol 
to eliminate an immediate hazard(s) to trial subjects without prior IEC/IRB 
approval/favourable opinion. 
The investigator may take appropriate urgent safety measures in order to protect the subjects of 
a clinical trial against any immediate hazards to their health or safety. However, the 
investigator must inform the sponsor/CRO within 24 hours of having taken such measures. 
The sponsor in turn shall immediately, and in any event no later than 3 days from the date the 
measures are taken, give written notice to the licensing authority and the relevant IEC/IRB of 
the measures taken and the circumstances giving rise to those measures. 
All urgent safety measures must be reported to the sponsor/CRO by using the SAE contact 
numbers listed in Section 10.1.1 within 24 hours of having to take such a measure(s). Such 
reports can be initiated by telephone but must be officially documented by the investigator (by 
email or fax) and must include details of what measures were taken and the circumstances 
giving rise to those measures. 
10.1.12 
Pregnancy Reporting 
This process is aimed at ensuring the appropriate monitoring of the potential risk related to 
IMP exposure of pregnant women and/or foetuses as well as the risks associated with exposure 
of a father, regarding congenital abnormalities or birth defects in their offspring. It also ensures 
compliance with applicable international and local regulations. 
The requirements are applicable to all subjects following exposure to IMP. 
Female trial subjects: The trial subject must be advised by the investigator to inform him/her 
immediately if she suspects she may be pregnant believes that conception occurred within 30 
days after IMP administration.  
Male trial subjects: The trial subject must be advised by the investigator to inform him/her 
immediately if he suspects his partner became pregnant within 30 days after IMP 
administration.  
When a trial subject reports a pregnancy (post-IMP administration) to the investigator, a 
pregnancy test should be arranged for the trial subject (or their partner) by the investigator 
within 7 days of the pregnancy being reported. 
The investigator must inform the sponsor/CRO within 24 hours of receiving positive 
pregnancy test results using a copy of the relevant CRF page (demography or AE). The 
investigator should include an estimated date of conception when communicating with the 
sponsor/CRO, as follow-up after end of pregnancy is required. 
A reported pregnancy will be followed to determine the outcome.  The investigator will collect 
follow-up information on the participant and the neonate and the information will be forwarded 
to the sponsor.  Generally, follow-up will not be required for longer than 6 to 8 weeks beyond 
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the estimated delivery date.  Any termination of pregnancy will be reported, regardless of 
foetal status (presence or absence of anomalies) or indication for the procedure. 
10.2 
Secondary Outcome Measures 
Dosimetry estimates and cumulated activity by source region and by entire body (including 
whole blood, plasma, and excreted urine) at time points up to 48 hours after administration in 
HVs. 
10.2.1 
Biodistribution 
One of the secondary objectives of this study is to determine the biodistribution of ioflupane 
(123I) injection after IV administration to Chinese HVs. Biodistribution data in HVs will consist 
of 123I activity in organs and tissues of interest at multiple time points, 123I activity in whole 
blood and plasma at multiple time points, and 123I activity in voided urine. The 123I activity in 
voided urine will be calculated as the product of the 123I activity measured in each void 
multiplied by the volume of that void. The absorbed doses of radiation to organs and tissues 
will be evaluated for the Cristy-Eckerman female and hermaphrodite male phantoms [Cristy 
and Eckerman 1987]. Descriptive statistics of absorbed doses to the target organs and tissues 
specified in the MIRD schema will be tabulated.  
Evaluation of radiation dosimetry outcome measures includes assessing the counts in ROIs 
from whole-body images, and the assay of radioactivity in whole blood, plasma, and urine. 
This will enable the following: 
 Estimation of whole-body retention of 123I at each imaging time point post-injection 
 Estimation of individual organ uptake, washout and retention of 123I at each imaging time 
point post-injection 
 Estimated clearance of administered 123I in whole blood and plasma 
 Estimation of elimination of 123I in blood and urine 
 Calculation of the absorbed radiation dose in target organs and tissues 
 Calculation of ED 
10.2.1.1 
Image Acquisition 
Whenever possible, images will be acquired at prespecified time points and without any 
interference in appropriate medical care; the latter will take priority. The sponsor will provide a 
detailed Imaging Manual to the site which contains a full description of planar and SPECT 
imaging procedures. 
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10.2.1.2 
Radioactive Counts in Region of Interest and Biodistribution Measurements 
In HVs, quantitative measurements of 123I activity in ROIs (including, but not limited to, lungs, 
heart, liver, gallbladder, spleen, kidneys, gastrointestinal tract and urinary bladder) will be 
made at several time points post-injection. Time-activity curves will be generated and 
integrated to obtain the cumulated activity in each region, and these values will be used to 
determine the internal radiation dosimetry by using the MIRD schema [Siegal et al 1999]. 
The temporal variations of 123I activity concentrations in whole blood and plasma and the rate 
and amount of 123I activity excreted through the urinary pathway will be measured. 
10.2.1.3 
Counting of 123I in Blood, Plasma, and Urine 
Ioflupane 123I activity in whole blood, plasma, and urine will be measured by using a gamma 
counter according to the working instructions at the site. Sample volumes will be adjusted to 
avoid counter saturation. For time points of blood and urine sampling, see Table 1. A full 
description of blood and urine collection procedures will be given in Imaging Manual. 
(a) 
Whole Blood and Plasma Assays 
For HVs, up to 5 mL venous blood samples will be taken at multiple time points to allow 
measurement of 123I content in whole blood and plasma over time.  
The maximum amount of blood taken for activity counting will be 55 mL for HVs. 
The up to 5 mL sample is withdrawn from the subject to a labelled collection tube, and the time 
of sampling is noted. The times at which samples will be assayed after collection will be 
specified in the Imaging Manual provided by the sponsor. The time at which the blood sample 
is taken and the time at which the 123I counting is started will be recorded in the radioactivity 
counting system, as will be the number of counts per specified time interval. The beginning of 
injection will be considered time zero. 
Following removal of an aliquot of blood for whole-blood activity counting, the remaining 
blood will be centrifuged to obtain plasma. Immediately thereafter, an aliquot of the resulting 
supernatant (i.e., plasma) will be transferred with a fresh disposable pipette to a pre-labelled 
tube for activity counting. The time at which the blood sample is taken and the time of 123I 
counting will be recorded in the CRF, as will be the number of counts per specified time 
interval in 0.5 mL plasma. The beginning of injection will be considered time zero. 
(b) 
Urine Assays 
Subjects will be asked to void from approximately 1 hour before IMP administration. Urine 
will be collected whenever voided up to a period of 48 hours post-administration. The total 
volume of the sample and the time of collection will be accurately recorded in the CRF. 
Radioactivity in each urine sample should be recorded in the CRF together with the volume 
measured, the total urine volume, and the time of measurement. The beginning of injection will 
be considered time zero. 
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10.2.2 
Assessment of Striatal Binding Ratio 
Left and right striatal binding ratios (SBR) will be determined from brain SPECT images 
acquired at 3 and 6 hours after administration. 
10.2.3 
Standard of Truth, Comparator, or Reference Imaging 
No standard of truth, comparator, or reference imaging will be used in this study. 
10.2.4 
Image Interpretation and Correlation with Standard of Truth 
Images obtained will be analysed by using ROIs in order to quantify counts in the organs of 
interest at prespecified time points. There will be no standard of truth in this trial as it is not a 
trial to assess diagnostic efficacy.  
10.2.5 
Radiation Dosimetry 
The calculation of radiation dosimetry will be done in accordance with the sponsor's SOP for 
radiation dosimetry studies, unless otherwise specified. For HV data, the absorbed doses per 
unit administered activity to organs and tissues will be estimated using the cumulated activities 
[Stabin et al 2005]. The ED per unit administered activity will be evaluated from this ensemble 
of absorbed dose data. A summary of the biodistribution and radiation dosimetry data will be 
presented in the clinical study report, and a full report produced by the sponsor. 
10.2.6 
Effective Dose 
A secondary objective of this study is to determine the ED of ioflupane (123I) injection after IV 
administration to Chinese HVs. The cumulative activities will be used to calculate the absorbed 
doses to organs and tissues per unit of administered activity [Stabin et al 2005]. The ED per 
unit of administered activity will be evaluated from this ensemble of absorbed dose data. 
10.3 
Other Variables 
Demographic data (age/date of birth, weight, height, BMI, sex and race) will be collected 
during the screening visit. Data on the subject's medical and surgical history will be collected 
at the screening visit. Data on the subject's concomitant medications will be collected from the 
screening visit to follow-up visit.  
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11 
DATA HANDLING AND QUALITY ASSURANCE 
11.1 
Completing and Signing Case Report Forms 
For electronic CRFs, data will be entered by trained site personnel, Any errors should be 
corrected within the electronic system. The audit trail will record all changes made, the date 
and time of the correction, and the person correcting the error. The appropriate electronic 
signature will be provided. 
11.2 
Clinical Data Management 
The sponsor or CRO will be responsible for the processing and quality control of the data. Data 
management will be carried out by the sponsor or CRO. The handling of data, including data 
quality control, will comply with all applicable regulatory guidelines. 
11.3 
Archiving 
All study documentation at the investigator site and sponsor site will be archived in accordance 
with ICH E6-GCP and the sponsor/CRO’s quality standards and SOPs. 
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12 
STATISTICAL METHODS AND PLANNED ANALYSIS 
The data will be analysed by the sponsor and/or designated CRO. Any data analysis carried out 
independently by the investigator should be submitted to the sponsor before publication or 
presentation. 
The data will be summarised with respect to demographic and baseline characteristics, safety 
observations and measurements, biodistribution, and radiation dosimetry. 
12.1 
General Statistical Considerations 
Tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed with SAS software, Version 9.2 or higher. Descriptive statistics for continuous 
data in summary tables will include the number of subjects in the analysis (n), mean, standard 
deviation, median, and range (minimum, maximum). Descriptive statistics for categorical data 
in summary tables will include counts and percentages. The last observation prior to 
administration of IMP will be used as the baseline value for calculating changes from baseline 
after administration of IMP. All data obtained on the CRF and entered into the database will be 
provided in separate data listings showing individual subject values. The planning and 
reporting of statistical analysis will be carried out as described in the sponsor/CRO’s SOPs 
governing clinical studies. 
12.2 
Populations for Analysis 
All subjects who receive ioflupane (123I) injection will be included in the safety analysis set.  
Subjects who receive ioflupane (123I) injection, undergo planar scintigraphy, have a complete 
set of images and complete blood sampling at prespecified timepoints will be included in the 
pharmacokinetic analysis set. Subjects who do not meet all of these criteria may be replaced. 
12.3 
Subject Demographics/Other Baseline Characteristics 
A table will be provided with the following information: 
 Number of subjects enrolled. 
 Number of subjects included in the safety analysis. 
 Number of subjects included in the pharmacokinetic analysis. 
 Number of subjects withdrawn from the study and the reason for withdrawal. 
Demographic information: Age, height, weight, and BMI will be summarised by using 
descriptive statistics. Sex and race will be summarised by counts and percentages. 
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Medical history will be summarised by counts and percentages.  
12.4 
Study Treatments 
IMP information, including the duration of the injection, saline flush volume, radioactivity and 
volume in syringe prior to administration, and total radioactivity administered, will be 
summarised.   
Any concomitant medication, including indication, given to a subject from 14 days prior to 
IMP administration throughout the follow-up visit at 2 weeks (± 2 days) after IMP 
administration, will be tabulated by counts and percentages using the World Health 
Organisation Drug Directory (WHO Drug), Version June 1, 2015 or later, and summarised by 
Anatomic Therapeutic Chemical Code Level 3 and preferred name.  
12.5 
Primary Analysis (Safety) 
All safety data will be listed by subject number and time point (if applicable). No confirmatory 
hypothesis testing is intended to be performed. P-values will be interpreted as a metric of 
uncertainty. All data will be listed by subject number and time point (if applicable). Confidence 
intervals, both individual and simultaneous, will be at the 95% confidence level unless 
otherwise noted. The last pre-administration observation will be used as the baseline value for 
calculating post-administration changes from baseline. 
An overall summary of AEs will be presented, and they will be coded with Medical Dictionary 
for Regulatory Activities (MedDRA) and summarised by MedDRA system organ class and 
preferred term.  
Observations and changes from baseline in the results of the physical examination, vital signs 
and oxygen saturation, 12-lead ECG, and clinical laboratory evaluation (haematology, serum 
biochemistry, and urinalysis) will be summarised (see Table 1). Other safety measures that will 
be summarised including results of tolerability questionnaire and injection site monitoring, and 
concomitant medications.   
12.5.1 
Clinical Laboratory Evaluation 
Descriptive statistics will be displayed for the observed values and changes from baseline. In 
addition, for each clinical laboratory variable and each time point, the following safety 
outcome measures will be summarised by counts and percentages: 
 The occurrence of 1 or more changes from baseline, at each post-administration time point, 
greater than 40% and 80% of the span of the normal limits (not applicable to qualitative 
parameters). 
 The occurrence of post-administration values outside the normal limits (not applicable to 
qualitative parameters). Shift tables based on the normal range will be prepared.  
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12.5.2 
Vital Signs and Oxygen Saturation 
Descriptive statistics will be displayed for the observed values and changes from baseline. For 
each vital sign and oxygen saturation variable and each time point, the following safety 
outcome measures will be summarised by counts and percentages: 
 The occurrence of 1 or more changes from baseline, at each post-administration time point, 
greater than a pre-specified magnitude (20 mm Hg for systolic blood pressure, 10 mm Hg 
for diastolic blood pressure, 10 beats/min for heart rate, 1.5°C for body temperature, 10 
breaths/min for respiration rate, and 5% for oxygen saturation). 
 The occurrence of post-administration values outside the normal limits (Section 15.3). Shift 
tables based on the normal range will be prepared.  
12.5.3 
Electrocardiograms 
Descriptive statistics will be displayed for the observed values and changes from baseline. For 
each ECG variable and each time-point, the following safety outcome measures will be 
summarised by counts and percentages: 
 The occurrence of 1 or more changes from baseline in the PR interval, at each post-
administration time point, within pre-specified increments of 4 ms (<4, 4 to 8, >8 to 12, 
and >12 ms), 10 ms (<10, 10 to 20, and >20 ms) and 25 ms (<25, 25 to 50, and >50 ms). 
 The occurrence of 1 or more changes from baseline in the QTc, QRS and RR interval at 
each post-administration time point within the following pre-specified increments: <30 ms, 
30 to 60 ms, and 60 ms increments for QTc interval; 50 ms, 50 to 100 ms, and 100 ms 
increments for QRS interval; 250 ms, 250 to 500 ms, and 500 ms increments for RR 
interval. 
 The occurrence of post-administration values outside the normal limits in the PR, QTc, 
QRS or RR interval (Section 15.3). Shift tables based on the normal range will be prepared.  
Two correction formulae will be employed in analysing QTc data in an attempt to reduce the 
bias resulting from over- or under-correction: 
 Bazett’s: QTcB = QT/RR 
 Fridericia’s: QTcF = QT/3RR 
ECGs for which the overall interpretation was abnormal will be summarised by counts and 
percentages at each post-administration time point. 
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12.5.4 
Physical Examination 
The number and percentage of subjects with changes in physical examination status from 
normal at baseline to abnormal at each post-administration time point (and vice versa) will be 
presented. Shift tables based on the normal range will be prepared.  
12.5.5 
Adverse Events 
The number and percentage of subjects with 1 or more AEs will be summarised. Summaries 
will also be presented by AE intensity and judged relationship to IMP.  
SAEs will be presented separately.  TEAE will be presented separately. 
Other significant AEs, will also be summarised. 
12.5.6 
Tolerability Questionnaire 
The results of the tolerability questionnaire performed pre- and post-injection will be 
summarised.  The boxplot of values over time will be plotted for each tolerability parameter. 
12.5.7 
Injection Site Monitoring 
The findings of injection site monitoring pre- and post-injection will be summarised. 
12.6 
Secondary Analysis 
12.6.1 
Biodistribution 
By using activity data from ROIs, data from the whole-body images, as well as activity data 
from serial blood and urine samples, descriptive statistics will be generated for biodistribution 
data (decay-corrected percentage administered activity per organ) at each time point for each 
organ and tissue of interest in HVs. Time-activity curves will then be generated from 123I 
activity data from all 8 subjects and integrated to obtain the normalised-cumulated activity in 
each source region, which will be summarised with descriptive statistics. The amount of 123I 
activity in plasma and excreted in urine will be calculated from the product of concentration of 
123I activity measured in each sample and the volume of each sample.   
The cumulative amount of 123I activity excreted in urine will be tabulated for each subject and 
summarised. In addition, the normalised cumulative activity in each source region will be 
compared between the Chinese subjects from this study and European subjects by using the 2-
sample t-test. 
SBR will be analysed to determine the stability of striatal uptake relative to a reference region 
over the proposed imaging window of 3 to 6 hours after administration. The difference 
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between the SBR at 3 and 6 hours calculated for each subject will be tested by Wilcoxon 
signed-rank test. 
12.6.2 
Radiation Dosimetry 
Descriptive statistics of absorbed doses to the target organs and tissues specified in the MIRD 
schema will be tabulated. In addition, the absorbed doses to these target organs and tissues will 
be compared between the Chinese subjects from this study and European subjects by using the 
2-sample t-test.   
12.6.3 
Effective Dose 
ED will be calculated according to ICRP methodology of ICRP publication 60 [ICRP 1991]. In 
addition, the ED will be compared between the Chinese subjects from this study and European 
subjects by using the 2-sample t-test. 
12.6.4 
Statistical Hypothesis, Model, and Method of Analysis 
No confirmatory hypothesis testing is intended to be performed in this study. 
12.6.5 
Handling of Missing Values/Censoring/Discontinuations 
Missing values will not be substituted by estimated values but treated as missing in the 
statistical evaluation. All data from all subjects dosed in the study will be included in all 
listings, plots, summary tables, and statistical analyses when appropriate. 
12.6.6 
Supportive Analyses 
No sensitivity analyses are currently planned in this study.  
12.6.7 
Handling of Uninterpretable Images 
The number of images that are uninterpretable will be displayed in tables.  
12.7 
Interim Analysis 
No interim analysis will be performed in this study. 
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12.8 
Sample Size Calculation 
No sample size calculations were performed. The number of subjects in this study was 
determined to fulfil local regulatory requirements. 
12.9 
Power for Analysis of Critical Secondary Variables 
No power calculations were made on any secondary variables.  
12.10 
Procedures for Missing, Unused and Spurious Data 
Missing values will not be substituted by estimated values but treated as missing in the 
statistical evaluation. All data from all subjects dosed in the study will be included in all 
listings, plots, summary tables, and statistical analyses when appropriate.  
12.11 
Rules for Excluding Subjects from Analysis 
All dosed subjects with a complete set of images will be included in the analyses unless 
otherwise specified. The sponsor will make any decisions regarding whether any subjects or 
any individual values belonging to a subject will be excluded from the evaluations when the 
protocol violation is considered to have a negative impact on the scientific aspects and 
interpretation of the study results.  Such judgments should be made in a blinded fashion before 
database lock and before any analyses have been performed. If the subject has received any 
IMP, all available safety data will be used. The reason(s) for any exclusion will be described in 
the report. 
12.12 
Procedures for Reporting Deviations from Original Statistical Plan 
Any deviations from the statistical analysis outlined in this protocol will be described, and 
reasons for the deviations listed, in the final Clinical Study Report. 
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13 
SPECIAL REQUIREMENTS AND PROCEDURES 
13.1 
Regulatory, Institutional and Ethical Review 
Before starting this study, the protocol (authorised by the sponsor) will be submitted to the 
regulatory bodies/local health authorities (in accordance with local regulations) and to the 
IEC/IRB for evaluation. The protocol will also be signed by the principal investigator before 
submission to the IEC/IRB. The study will not start before the IEC/IRB gives written approval 
or a favourable opinion in accordance with ICH E6-GCP and all applicable regulatory 
bodies/local health authorities give approval or a favourable opinion as required. 
No changes from the final approved (authorised) protocol will be initiated without the 
IEC’s/IRB’s prior written approval or favourable opinion of a written amendment, except when 
necessary to eliminate immediate hazards to the subjects or when the change involves only 
logistics or administration. The sponsor will authorise and the principal investigator(s) will 
sign the protocol amendment prior to submission to the IEC/IRB. Protocol amendments should 
be submitted to the IEC/IRB without delay. Any significant deviation from the protocol when 
no approved amendment exists will be regarded as a protocol violation and will be addressed 
as such during the reporting of the study. 
13.2 
Investigator’s Responsibilities 
13.2.1 
Overall Responsibilities 
The investigator(s) is/are responsible for conducting the study in full accordance with the 
Protocol and the Declaration of Helsinki, the Good Clinical Practice: Consolidated Guideline, 
approved by the ICH, and any applicable national and local laws and regulations. Information 
regarding any investigational centres participating in this study that cannot comply with these 
standards will be documented. 
13.2.2 
Subject Informed Consent 
Written and oral information about the study in a language understandable by the subject will 
be given to all subjects. Each subject’s willingness to participate in the study will be 
documented in a signed and dated informed consent form before any procedures or 
assessments are done and after the aims, methods, anticipated benefits, potential hazards, and 
insurance arrangements in force are explained. It will also be explained to the subjects that they 
are free to refuse entry into the study and free to withdraw from the study at any time without 
prejudice to future treatment. The informed consent process will be documented in the subject's 
medical record and the investigator will sign, date, and time the informed consent form after 
the subject has signed, dated, and recorded the time. The investigator(s) will keep the original 
consent forms, and copies will be given to the subjects. 
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13.2.3 
Direct Access to Source Data/Documents 
The monitor(s), auditor(s), authorised personnel of the sponsor/CRO, health authority 
inspector(s) or their agents, and authorised members of IECs/IRBs will be given direct access 
to source data and documentation (e.g., medical charts/records, laboratory results, printouts, 
videotapes, etc.) for source data verification, provided that subject confidentiality is maintained 
in accordance with local requirements. 
13.2.4 
Confidentiality Regarding Study Subjects 
The investigator(s) must assure that the privacy of the subjects, including their personal 
identity and all other personal medical information, will be maintained at all times. In CRFs 
and other documents or image material (including materials from all examinations) submitted 
to the sponsor/CRO, subjects will not be identified by their names, but by an identification 
code (e.g., study subject number). 
Personal medical information may be scrutinised for the purpose of verifying data recorded in 
the CRF. This may be done by the monitor(s), properly authorised persons on behalf of the 
sponsor, the quality assurance unit, or regulatory authorities. Personal medical information will 
always be treated as confidential. 
13.3 
Protocol Deviations 
Any deviation from the protocol when no approved amendment exists must be documented as 
a protocol deviation and reported according to local requirements. If appropriate, corrective 
and preventative action must be implemented to avoid repetition. Protocol deviations and any 
potential impact on the study results will be discussed during the reporting of the study. 
Waivers or protocol exceptions will not be granted prospectively by the sponsor under any 
circumstances. 
13.4 
Study Monitoring 
Study monitoring will be performed in accordance with ICH E6-GCP, the sponsor/CRO SOPs, 
the protocol, and applicable local regulations. 
13.5 
Audit and Inspection 
According to ICH E6-GCP, the sponsor or regulatory authorities may audit the investigational 
site. The sponsor’s Quality Assurance Unit, independent of the Clinical Research and 
Development Department, is responsible for auditing the study. 
The investigator(s) must accept that regulatory authorities may conduct an inspection to verify 
compliance of the study with GCP. 
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13.6 
Insurance 
This study is covered under the sponsor’s Liability Insurance Policy (under General Electric 
Insurance Company and/or a company designated by the study sponsor). A Certificate of 
Insurance and/or an information leaflet containing essential information about the insurance 
coverage can be provided upon request. 
13.7 
Publication Policy 
The investigator and/or Institution shall have the right to publish the results of their work 
conducted under this protocol, subject to providing the sponsor with the opportunity to review 
the contents of any proposed abstract or publication concerning the work, including any results 
of the study, in advance of publication and if necessary to delay publication for a limited time 
not to exceed 60 days in order to protect the confidentiality or proprietary nature of any 
information contained therein. The sponsor will make every reasonable effort to consider and 
release each proposed publication within 30 days, or proposed abstract within 15 days, of 
submission. 
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14 
REFERENCES 
[Cristy and Eckerman 1987] 
Cristy M, Eckerman KF. Specific absorbed fractions of energy at various ages from internal 
photon sources. Volume I-VII. Report ORNL/TM-8381. Oak Ridge: TN: Oak Ridge National 
Laboratory; 1987. 
[Study CY 95.FP.1] 
A single centre, open study of an intravenous dopamine transporter ligand containing 111MBq 
[123I]FP-CIT, in healthy volunteers to examine biodistribution, safety and tolerability. Phase I, 
protocol number CY 95.FP.I. Final clinical study report: 19th August, 1998.  
[Frear 1998] 
Frear TJB (1998) A single centre, open study of an intravenous dopamine transporter ligand 
containing 111 MBq [123I]FP-CIT, in healthy volunteers to examine biodistribution, safety and 
tolerability. Phase I, Protocol number CY95.FP.I).  Nycomed Amersham internal report, dated 
19th August 1998. 
[ICRP 1991] 
1990 Recommendations of the International Commission on Radiological Protection. ICRP 
Publication 60. 1991. Ann. ICRP; 21:1-3. 
[Siegal et al 1999] 
Siegal J, Stubbs TS, Stabin M et al. MIRD Pamphlet No. 16: Techniques for quantitative 
radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation 
dose estimates. J Nucl Med 1999;40: 37S-61S. 
[Stabin et al 2005] 
Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: The second-generation personal computer 
software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46(6):1023-1027. 
[Takano et al 1999] 
Takano K, Matsumura K, Watanabe Y, Yamada T, Kubo H, Naitou Y, et al. Phase 1 Clinical 
Study of 123I-FP-CIT, a New Radioligand for Evaluating Dopamine Transporter with SPECT 
(I): Biodistribution and Absorbed Dose. Kaku Igaku 1999 Sep;36(7):735-44. 
[Ziquiang et al 1994] 
Ziquiang P, Zhenyum H, Yin Y, Mingquiang G. Natural background radiation and population 
dose in China. Radioprotection 1994;29(1):69-80. 
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15 
APPENDICES 
15.1 
Information on Investigational and Registered Products 
The reference document for this study is the current version of the European Union Summary 
of Product Characteristics approved by the European Medicines Agency. The reference 
document provides up-to-date information on the efficacy and safety of the IMP and is used for 
assessing expectedness of Serious Adverse Drug Reactions, in order to determine regulatory 
reportability. An unexpected adverse drug reaction is a reaction for which the nature, 
seriousness, severity, or outcome is not consistent with the applicable product information.  
15.2 
Equipment Parameters 
Please refer to the Imaging Manual. 
15.3 
Normal Limits for Vital Signs, Oxygen Saturation and ECG 
Intervals 
Table 3 
Criteria for Normal Limits for Vital Signs 
and Oxygen Saturation 
Vital Signs Parameter 
Normal Limits 
Low 
High 
Systolic BP (mm Hg) 
85 
139 
Diastolic BP (mm Hg) 
60 
89 
Heart rate (beats/minute) 
60 
100 
Respiration rate (breaths/minute) 
12 
22 
Body Temperature 
36.4C 
97.5F 
37.7C 
99.5F 
Oxygen saturation (%) 
93 
100 
a Changes in body weight are evaluated by the investigator (without 
taking height into account) since BMI is not collected on the CRF. 
b BMI is calculated and analysed retrospectively by the sponsor, at 
which time height is taken into account. 
 
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Table 4 
Criteria for Normal Limits for ECGs 
 
Normal Limits (ms) 
ECG Variable 
Low 
High 
PR interval 
120 
200 
QRS interval 
50 
100 
RR interval 
600 
1000 
QT interval 
(Sex not specified) 
— 
440 
QTc intervala 
(Sex not specified) 
— 
440 
a No lower boundary set for QTc. 
15.4 
Tolerability Questionnaire 
Before and after the administration of DaTSCAN™ Injection, please ask the subject to mark on 
the line below how he/she is feeling with a single line (not a cross), to record the status of 
mood, pain at injection site, itchiness of injection site, loss of function at injection site, and 
quality of sleep, using Visual Analog Scale (VAS) method*. 
 
Mood: 
 
 
 
 
Pain at Injection Site: 
 
 
 
 
Itchiness of Injection Site: 
 
 
 
0mm 
Bad 
100mm 
Good 
0mm 
Normal 
100mm 
Painful 
0mm 
Normal 
100mm 
Itchy 
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Loss of Function at Injection Site 
 
 
 
 
Quality of Sleep#:                                                              
 
 
 
*Visual Analog Scale (VAS) is a continuous scale comprised of a horizontal line, usually 10 centimetres (100 mm) in length, 
anchored by 2 verbal descriptors: “0” stands for normal, and 100 mm stands for each symptom extreme, or “0” stands for bad, 
and 100 mm stands for good. 
# At -1h (± 10 min), assessment is based on how subject feels during past 2 weeks’ sleep quality; At 15mins (± 5 
min), 1h (± 10 min), 4h (± 10 min), assessments seem to be not applicable; At 24h (± 2 h), assessment is based on 
quality of first sleep after IMP injection; At 48h (± 3 h), assessment is based on quality of second sleep after IMP 
injection.  
 
Tolerability Questionnaire Scoring Table 
 
Tolerability Questionnaire Timepoint& 
-1h  
(± 10 min) 
15min  
(± 5 min) 
1h 
 (± 10 min) 
4h  
(± 10 min) 
24h  
(± 2 h) 
48h 
 (± 3 h) 
Mood 
 
 
 
 
 
 
Pain at Injection Site 
 
 
 
 
 
 
Itchiness of Injection Site 
 
 
 
 
 
 
Loss of Function at 
Injection Site 
 
 
 
 
 
 
Quality of Sleep 
 
 
 
 
 
 
h = hours, min = minutes 
&15mins, 1h, 4h, 24h, 48h mean various timepoints post administration of IMP. -1h means 1 hour before the administration of 
IMP. 
0mm 
Bad 
100mm 
Good 
0mm 
Normal 
100mm 
Loss of 
function 
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Scoring Implication 
Mood 
Bad – 0mm 
Good – 100mm 
Pain at Injection Site 
Normal – 0mm 
Painful – 100mm 
Itchiness of Injection Site 
Normal – 0mm 
Itchy – 100mm 
Loss of Function at Injection Site 
Normal – 0mm 
Loss of Function – 100mm 
Quality of Sleep 
Bad – 0mm 
Good – 100mm 
 
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16 
CLINICAL PROTOCOL AMENDMENT SUMMARIES 
16.1 
Amendment A01 
16.1.1 
Reasons for Amendment 
The China Center for Drug Evaluation requested that GE Healthcare evaluate the Study GE-
001-023 protocol according to the ICH E5 requirement.  As a result, changes have been 
incorporated to provide better characterisation of DaTSCAN™ in the Chinese population.  
Furthermore, available data from the Takano study will be used for comparison between 
Chinese and Japanese subjects. 
16.1.2 
Summary of Key Changes 
Addition: 
 Results from SPECT imaging performed at 3 and 6 hours to support label wording of 
imaging at 3 to 6 hours after DaTSCAN™ administration. 
 Exclusion criteria for radionucleotide injection within 2 weeks prior to the imaging visit. 
 Exit visit 2 weeks (± 2 days) after DaTSCAN™ injection – Compliance of M3 
(requirement for adequate follow-up for women of childbearing potential) and longer safety 
follow-up for all subjects. 
Changed: 
 Minimum age for subjects enrolled in the study changed from 40 to 50 years. 
Deletion: 
 Planar imaging at 3 hours to make way for SPECT imaging at 3 hours. 
 Electroencephalogram, since this is not the first-in-man study, no abnormalities have been 
detected in the past, and there is no safety concern of epilepsy in European Union Summary 
of Product Characteristics. 
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16.2 
Amendment A02 
16.2.1 
Reasons for Amendment 
This Protocol Amendment is to provide further explanation and clarification to certain items in 
the protocol and to avoid potential ambiguity of interpretation. Meanwhile, some content was 
revised according to idiomatic expression. 
16.2.2 
Summary of Key Changes 
Addition: 
 Added content regarding the Tolerability Questionnaire Interview. 
 Added serum biochemistry and haematology parameters. 
 Added that TEAEs will be presented separately. 
Changed: 
 The GE Healthcare UK address and Medical Director details were updated. 
 Updated the dose of “111 MBq” and “range from 100 to 122 MBq” to “111 MBq ± 10%”.  
The maximum volume was changed from 3 mL to 5 mL. 
 Clarification of study visits included in the study and timing of events was provided 
throughout. 
 Revised “abnormalities” with “tests” instead for clinical laboratory test; Remove 
“abnormalities” for physical examination and ECG, and added “results” for "physical 
examination", "clinical lab test", "Injection site monitoring", "vital signs" and "ECG". 
 Revised “all urine” to “each urine” at the sentence of “All urine excreted from 1 hour 
before administration of ioflupane (123I) injection to 48 hours after administration will be 
collected as voided.” 
 Updated with information from the DaTSCAN™ IB and the study Imaging Manual, 
including removal of 2.5 mL DaTSCAN™ vials. 
 Updated the enrolment start date from 2018 to 2020. 
 Updated exclusion criteria to keep consistence with Study GE-001-024 and align with 
current standards. 
 Updated handling of withdrawals for AEs. 
 Updated thyroid blocking procedures. 
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 AE monitoring and reporting of AEs were updated. 
Deletion: 
 Removed inclusion of Japanese healthy volunteer data for comparison. 
 Removed 5 mL of plasma samples. 
 Removed prior medications and pre-treatment AEs. 
 Removed age requirement that half of the subjects would be in the 50-70 years category. 
 Removed the maximum blood volume for sample collection; removed “central laboratory”. 
 
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6,*1$785(3$*(
Date / Name
Justification / Role
Signed By: Shamsul Mohammed Alam
Date of signature: 03-Feb-2020 21:18:57 GMT+0000
Justification: Approved
Role: Head of Biometrics
Signed By: Francois Tranquart
Date of signature: 04-Feb-2020 07:24:28 GMT+0000
Justification: Approved
Role: Head of Clinical Development
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