Clinical trial NCT05636852
Conditions: Parkinson Disease Movement Disorders
Keywords: SPECT Altropane Parkinson's disease Parkinsonian syndromes movement disorders striatum dopamine transporter
Sponsor: GE Healthcare
Start date: 2023-04-24; Completion date: 2024-06-08
Enrollment: 15 participants; Allocation: NA; Intervention model: SEQUENTIAL

Brief summary:
Previous studies showed that a dose of 8 millicuries of Altropane was appropriate for imaging patients with suspected Parkinson's disease. This study determined if a lower dose (5 millicuries) would suffice.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Altropane (123I) Injection
Intervention descriptions: intervention 1: Each participant received a single intravenous (IV) administration of 5 millicuries (mCi) (185 megabecquerels \[MBq\]) of Altropane (123I) Injection on Day 1. Altropane SPECT images were acquired for 30 minutes starting 15 to 20 minutes after administration with Altropane. These images were visually interpreted by 5 expert independent blinded readers.

Protocol documents:
Prot_000.pdf: 
GE HealthCare Confidential 
Page 1 of 88 
Clinical Study Protocol 
GE HealthCare 
GE-278-001 
Title: An open-label multicenter Phase 2 dose-evaluation study of Altropane (123I) Injection for 
striatal dopamine transporter visualization using SPECT brain imaging 
REVISED TO INCORPORATE AMENDMENT A02 
Sponsor 
GE HealthCare Ltd. and its Affiliates (hereinafter referred to as the “Sponsor”) 
GE HealthCare 
251 Locke Drive 
Marlborough, MA 01752 USA 
IND NUMBER: 052079 
Medical Director 
Clinical Development 
GE HealthCare Life Sciences 
251 Locke Drive 
Marlborough, MA 01752 
Mobile: 
Email: 
GE HealthCare Confidentiality Statement 
This protocol is provided for conducting a clinical research study. The information contained in 
this document is confidential and cannot be disclosed without written authorization of GE 
HealthCare, except to the extent necessary to obtain informed consent or IRB approval, or 
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. 
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023
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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 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
Title of Study:  An open-label multicenter Phase 2 dose-evaluation study of Altropane (123I) Injection for 
striatal dopamine transporter visualization using SPECT brain imaging  
Protocol Number:  GE-278-001 
Investigators and Study Centers: Up to 5 centers in the United States 
Phase of Development: 2 
Objectives:  
Note: Altropane (123I) Injection is hereafter referred to as Altropane. 
Primary Objective: 
•
To determine whether a 5-mCi dose of Altropane is acceptable for visualizing the right and left striata.
Secondary Objectives: 
•
To evaluate the safety of Altropane (using the endpoints adverse event [AE] and serious AE [SAE]
frequency, and changes from baseline in vital signs, physical examination, electrocardiogram [ECG], and
laboratory parameters).
Study Design:  
Altropane is a diagnostic radiopharmaceutical under development for striatal dopamine transporter (DAT) 
visualization using single photon emission computed tomography (SPECT) brain imaging, to assist in the 
evaluation of adult patients with suspected Parkinsonian syndromes (PS). Data from a prior clinical study show 
that an 8-mCi (296-MBq) Altropane dose provides images of diagnostic quality in patients with suspected PS. 
This open-label Phase 2 dose evaluation study will determine if a 5-mCi (185-MBq) dose would also result in 
diagnostic-quality images. The study will evaluate a 5-mCi dose in up to 2 groups of subjects, in up to 2 parts. 
In Part 1, consenting subjects who have a DaTscan image showing normal striatal uptake and who have a 
consistent clinical diagnosis will be scheduled to undergo striatal SPECT with 5 mCi of Altropane 
administered intravenously. If the visual interpretation of the striatal images of these subjects is concluded not 
to be acceptable, then Part 2 will not be conducted, the study will end, and the 8-mCi dose will be selected for 
further clinical development. However, if the visual interpretation is acceptable, then the study will proceed to 
Part 2. 
In Part 2, consenting subjects who have a DaTscan image showing abnormal striatal uptake and who have a 
consistent clinical diagnosis (degenerative PS [dPS]) will be scheduled to undergo striatal SPECT with 5 mCi 
of Altropane administered intravenously. If the visual interpretation of the striatal images from the dPS 
subjects is not acceptable, then the 8-mCi dose will be selected. However, if the visual interpretation is 
acceptable, then the 5-mCi dose will be selected. 
At least 10 subjects with normal striatal uptake on DaTscan images will be recruited in Part 1. If Part 2 
proceeds (dependent on the results of Part 1), then additionally at least 20 subjects with abnormal striatal 
uptake on DaTscan images (dPS subjects) will be recruited. Thus, the total number of subjects will be at least 
10, or, if Part 2 is conducted, at least 30. 
Altropane SPECT images will be acquired for 30 minutes starting 15 to 20 minutes after dosing. Safety will be 
monitored continuously throughout the study and at a 24-hour follow-up telephone call after Altropane 
imaging. The anticipated effective radiation dose of Altropane from a 5-mCi dose is 4.09 mSv. 
Visual interpretation of the Altropane SPECT images will be conducted by 5 independent expert readers who 
are blinded to each subject’s clinical information, and who are not otherwise involved in the study. Their visual 
image interpretations will be a forced choice between normal (caudate and putamen fully visible on left and 
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Name of Sponsor/Company: 
GE HealthCare Ltd. and its Affiliates 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
right, or with small insignificant defects) or abnormal (unilateral or bilateral reduced) striatal uptake. Readers 
will also evaluate their confidence in striatal visualization, rating it as high, medium, or low, and will assess 
image quality (as excellent, good, fair, poor, or unevaluable). 
The dose selection decision will be based on consideration of all of the available data acquired within the 
study. 
Selection of Subjects: 
Inclusion Criteria: 
Patients may be included in the study if they meet all of the following criteria: 
(1) For Part 1: a) the patient has a DaTscan image, obtained within 1 year (preferably within 6 months) 
before screening, that shows normal striatal uptake and b) the patient has a clinical diagnosis (made by a 
board-certified neurologist who is qualified by training and experience in the diagnosis of movement 
disorders) that is consistent with the DaTscan image.  
For Part 2 (if applicable): a) the patient has a DaTscan image, obtained within 1 year (preferably within 6 
months) before screening, that shows abnormal (unilateral or bilateral reduced) striatal uptake and b) the 
patient also has a confirmed clinical diagnosis of a dPS (such as Parkinson’s disease, multiple system 
atrophy, corticobasal degeneration, progressive supranuclear palsy, etc.) made by a board-certified 
neurologist who is qualified by training and experience in the diagnosis of movement disorders, and c) the 
diagnosis is consistent with the DaTscan image. 
(2) The patient is male or female, ≥18 years of age, of any race and ethnicity. 
(3) The patient is able and willing to comply with study procedures and signed and dated informed consent is 
obtained.  
(4) If the patient is a woman of childbearing potential*, she must use a highly effective method of 
contraception** from Screening until 30 days after the last administration of Altropane, and the results of 
a serum or urine human chorionic gonadotropin pregnancy test, performed at Screening and on the day of 
Altropane administration (with the result known before Altropane administration), must be negative. 
(5) If the patient is a male*** with a sexual partner who is a woman of childbearing potential*, he and his 
partner must use adequate contraception** from Screening until 30 days after the last administration of 
Altropane.  
* A woman of childbearing potential is neither post-menopausal nor surgically sterile. Post-menopausal means
having had no menses for at least 12 months without an alternative medical cause. Surgically sterile means 
having had a documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or any 
combination of these. 
** A highly effective method of contraception is one that has a failure rate of less than 1% per year when used 
consistently and correctly; such methods include combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only 
hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine 
device; intrauterine hormone-releasing system; bilateral tubal ligation/occlusion; vasectomized partner (with 
medical confirmation of success); and abstinence from heterosexual intercourse involving a woman of 
childbearing potential.  
*** A male is considered fertile after puberty unless permanently sterile by bilateral orchidectomy, or 
vasectomized with confirmation of success. 
Exclusion Criteria: 
Patients must be excluded from participating in this study if they meet any of the following criteria: 
(1) The patient was previously included in this study. 
(2) Fewer than 7 disintegration half-lives have elapsed between the patient’s last procedure (therapeutic or 
diagnostic) involving a radioisotope and Visit 2 (altropane SPECT imaging). 
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Name of Sponsor/Company: 
GE HealthCare Ltd. and its Affiliates 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
(3) Including participation in this study, the patient’s total exposure to radiation during medical 
procedures/tests in the past year would exceed 50 mSv. 
(4) The patient has participated in an investigational drug or device clinical trial within 30 days before the 
date of informed consent. 
(5) The patient has any clinically significant or unstable physical or psychological illness, structural brain 
abnormality, abnormal laboratory results, or abnormal ECG (based on medical history or physical 
examination at Screening), as determined by the Principal Investigator, that would interfere with study 
participation. 
(6) The patient has any history of drug or alcohol abuse in the 2 years prior to the date of informed consent. 
(7) The patient has a positive urine screen for drugs of abuse at Screening. 
(8) The patient is a pregnant or breast-feeding female, or is a female of child-bearing potential that is not 
using appropriate birth control. 
(9) The patient is unable to lie supine for 1 hour. 
(10) The patient has any thyroid disease other than adequately treated hypothyroidism. 
(11) The patient has known or suspected allergy/hypersensitivity to any ingredient in Altropane or to the 
thyroid blocking medication to be used before imaging. 
(12) The patient is currently taking any of the medications/treatments listed in the Concomitant Medication 
List as disallowed and cannot or will not discontinue use at least 12 hours prior to SPECT exam.  
(13) The patient was referred to DaTscan imaging for evaluation of possible cognitive impairment including 
dementia. 
Number of Subjects/Centers Planned: At least 10 subjects with normal striatal uptake on DaTscan images 
will be recruited in Part 1. If Part 2 proceeds (dependent on the results of Part 1), then additionally at least 20 
subjects with abnormal striatal uptake on DaTscan images (dPS subjects) will be recruited. Thus, the total 
number of subjects will be at least 10, or, if Part 2 is conducted, at least 30. Up to 5 centers in the United States 
will be utilized for the study. 
Treatment of Subjects 
Investigational Medicinal Product: Altropane (123I) Injection (referred to as Altropane), 5 mCi, administered 
intravenously.  
Control: None. 
Adjunctive Drugs: Thyroid blocking medication will be administered orally at least 1 hour ± 15 minutes 
before administration of Altropane, unless institutional protocols dictate otherwise.  
Duration of Treatment: The study will require 2 visits for each subject. Each subject will attend a screening 
visit (Visit 1) within 30 days before the SPECT visit (Visit 2).  There will be a 24-hour safety follow-up phone 
call after Visit 2. 
Efficacy and Safety Variables 
Part 1: 
Primary Efficacy Endpoint:  
•
Striatal visualization, reported as a forced choice of either normal (caudate and putamen fully visible on
left and right, or with small insignificant defects) or abnormal (unilateral or bilateral reduced) striatal
uptake.
Secondary Efficacy Endpoints 
•
Reader confidence in striatal visualization
•
Reader assessment of image quality
•
Inter-reader agreement
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Name of Sponsor/Company: 
GE HealthCare Ltd. and its Affiliates 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
Secondary Safety Endpoints: 
•
Subjects reporting 1 or more AE
•
Adverse drug reaction (ADR) frequency
•
Changes from baseline in vital signs, physical examination, ECG, or laboratory parameters.
Part 2 (if applicable): 
Primary Efficacy Endpoint: 
•
Striatal visualization, reported as a forced choice of either normal (caudate and putamen fully visible on
left and right, or with small insignificant defects) or abnormal (unilateral or bilateral reduced) striatal
uptake
Secondary Efficacy Endpoints 
•
Reader confidence in striatal visualization
•
Reader assessment of image quality
•
Inter-reader agreement
•
Intra-reader reproducibility (including the images from Part 1)
Secondary Safety Endpoints: 
•
Subjects reporting 1 or more AE
•
ADR frequency
•
Changes from baseline in vital signs, physical examination, ECG, or laboratory parameters
Statistical Methods and Planned Analysis:  
Sample Size Calculation: 
Based on prior experience with an approved DAT imaging agent (DaTscan), it is expected that the probability 
of a correct subject classification based on Altropane images will be 92% in Part 1 and 91% in Part 2 (if it is 
conducted). 
In Part 1, 10 subjects with normal striatal uptake will be sufficient to determine whether or not the 5-mCi 
Altropane dose provides acceptable visualization of normal striatal uptake. Ten subjects with normal striatal 
uptake can achieve 62% power to detect whether the 5-mCi dose can result in a rate of correct subject 
classification of 70% or higher by a 1-sided exact test at a target significance level of 0.04. These results 
assume that the true rate of correct subject classification under the null hypothesis is 92% in Part 1.  
If Part 2 proceeds, then 20 subjects with abnormal striatal uptake will be sufficient to determine whether or not 
to proceed with the 5-mCi dose in Phase 3. Twenty subjects with abnormal striatal uptake will have 76% power 
to detect whether the 5-mCi dose can result in a rate of correct subject classification of 75% or higher under the 
assumption that the true rate of correct subject classification is 91%. 
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Name of Sponsor/Company: 
GE HealthCare Ltd. and its Affiliates 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
Analysis Populations: 
The Safety Analysis Set is defined as all subjects who receive any amount of Altropane. 
The Full Analysis Set is defined as all subjects who receive any amount of Altropane and have an Altropane 
image interpretation.   
For Part 1 the dose-evaluation (efficacy) analysis will be based on the Full Analysis Set. For Part 2 (if 
conducted) the dose-evaluation (efficacy) will also be based on the Full Analysis Set. 
Primary Efficacy Analyses: 
•
Number and percentage of correct classifications of 5-mCi Altropane images from subjects with normal
striatal uptake (Part 1)
•
Number and percentage of correct classifications of 5-mCi Altropane images from subjects with abnormal
striatal uptake (Part 2, if applicable)
The correctness of image classification will be determined from the majority interpretation of the 5 expert 
blinded readers (at least 3 of 5 readers). 
The 5-mCi dose will be considered to show acceptable striatal visualization if the percentage of correct 
majority classifications is greater than 70% in Part 1 and 75% in Part 2 (if applicable). 
Secondary Efficacy Analyses: 
Reader Assessment of Image Quality 
•
Number and percentage of Part 1 subjects with 5-mCi Altropane image quality judged as excellent or good
•
Number and percentage of subjects in Part 2 (if applicable) with 5-mCi Altropane image quality judged as
excellent or good
The quality will be graded as excellent, good, fair, poor, or unevaluable. The results of this secondary analysis 
will be considered consistent with the results of the primary analysis if the percentage of images with excellent 
or good majority ratings is greater than 70%.  
Reader Confidence in Striatal Visualization 
•
Number and percentage of Part 1 subjects with high confidence ratings for their 5-mCi Altropane images
•
Number and percentage of Part 2 subjects (if applicable) with high confidence ratings for their 5-mCi
Altropane images
The confidence level will be graded as high, medium, or low. The results of this secondary analysis will be 
considered consistent with the results of the primary analysis if the percentage of images with high majority 
ratings of confidence is at least 70%.  
Inter-Reader Agreement 
•
Number and percentage of images for which 5, 4, and 3 readers, respectively, are in agreement on the
subject classification for Part 1, and, if applicable, Part 2.
Intra-Reader Reproducibility (Part 2 Only) 
•
Number and percentage of subjects for whom each reader’s second image interpretation agrees with
his/her first image interpretation.
If Part 2 is conducted, each reader will read all images (including the images from Part 1) at least twice to 
determine intra-reader reproducibility. 
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Name of Sponsor/Company: 
GE HealthCare Ltd. and its Affiliates 
Name of Finished Product: 
Altropane (123I) Injection 
Name of Active Ingredient: 
[123I]Altropane 
Secondary Safety Analyses: 
The following applies to Part 1, and, if conducted, to Part 2. Safety analyses will be performed for treatment-
emergent AEs, treatment-emergent SAEs, ADRs, serious ADRs, vital signs, physical examination, ECG, and 
laboratory tests.  
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2 
TABLE OF CONTENTS 
2.1 
Overall Table of Contents 
Page Number 
1 
SYNOPSIS ..................................................................................................................... 3 
2 
TABLE OF CONTENTS ............................................................................................... 9 
2.1 
Overall Table of Contents .................................................................................. 9 
2.2 
List of Tables .................................................................................................... 12 
2.3 
List of Figures ................................................................................................... 12 
3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................. 13 
4 
BACKGROUND INFORMATION ............................................................................. 14 
5 
STUDY OBJECTIVES AND ENDPOINTS ............................................................... 16 
5.1 
Objectives ......................................................................................................... 16 
5.2 
Study Endpoints ................................................................................................ 16 
5.2.1 
Study Endpoints for Part 1 ............................................................. 16 
5.2.2 
Study Endpoints for Part 2 (If applicable) ...................................... 17 
6 
STUDY DESIGN ......................................................................................................... 18 
6.1 
Overall Study Design and Plan ......................................................................... 18 
6.2 
Scientific Rationale for Study Design .............................................................. 21 
6.3 
Study Timeframe .............................................................................................. 24 
6.4 
End of Study Definition .................................................................................... 24 
6.5 
Risks and Benefits to Subjects.......................................................................... 24 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS................................................ 26 
7.1 
Procedures for Enrollment ................................................................................ 26 
7.2 
Inclusion Criteria .............................................................................................. 26 
7.3 
Exclusion Criteria ............................................................................................. 27 
7.4 
Screen Failures ................................................................................................. 28 
7.5 
Withdrawal and Termination Criteria............................................................... 28 
7.5.1 
Subject Withdrawal ........................................................................ 28 
7.5.2 
Subject Lost to Follow-Up ............................................................. 29 
7.5.3 
Study or Site Termination .............................................................. 29 
8 
TREATMENT OF SUBJECTS .................................................................................... 30 
8.1 
Investigational Medicinal Products .................................................................. 30 
8.1.1 
Investigational Medicinal Product: Altropane (123I) Injection ....... 30 
8.1.2 
Comparator ..................................................................................... 31 
8.1.3 
Adjunctive Product: Thyroid Blocking Medication ....................... 31 
8.1.4 
Altropane Accountability ............................................................... 31 
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8.1.5 
Registration of Product Complaints ............................................... 32 
8.2 
Method of Numbering Subjects ........................................................................ 32 
8.3 
Selection of Doses and Timing ......................................................................... 32 
8.4 
Randomization and Blinding ............................................................................ 33 
8.5 
Prior and Concomitant Medications or Procedures .......................................... 33 
8.5.1 
Prohibited Medications ................................................................... 33 
8.6 
Contraception and Pregnancy Avoidance Procedure ....................................... 34 
8.7 
Treatment Compliance ..................................................................................... 35 
9 
STUDY PROCEDURES .............................................................................................. 36 
9.1 
Screening Visit (Visit 1) ................................................................................... 39 
9.2 
SPECT Imaging Visit (Visit 2) ......................................................................... 39 
9.3 
24-hour Follow-Up (Visit 3) ............................................................................ 41 
9.4 
Unscheduled Visits ........................................................................................... 41 
10 
EFFICACY, SAFETY, AND OTHER ASSESSMENTS ............................................ 42 
10.1 
Efficacy Assessments ....................................................................................... 42 
10.1.1 
Image Acquisition .......................................................................... 42 
10.1.2 
Image Interpretation and Correlation with Standard of Truth ........ 42 
10.2 
Safety Assessments .......................................................................................... 42 
10.2.1 
Clinical Laboratory Evaluation ...................................................... 43 
10.2.2 
Vital Signs ...................................................................................... 44 
10.2.3 
Electrocardiograms ......................................................................... 44 
10.2.4 
Limited Physical Examination ....................................................... 44 
10.2.5 
Adverse Events and Serious Adverse Events ................................. 45 
10.2.6 
Urgent Safety Measures.................................................................. 51 
10.2.7 
Pregnancy Reporting ...................................................................... 51 
10.3 
Other Variables ................................................................................................. 52 
10.3.1 
Demographic Data .......................................................................... 52 
10.3.2 
Medical and Surgical History ......................................................... 52 
10.3.3 
Prior and Concomitant Medication................................................. 53 
10.3.4 
Drug Screening ............................................................................... 53 
10.4 
Appropriateness of Measurements ................................................................... 53 
11 
DATA HANDLING AND QUALITY ASSURANCE ................................................ 54 
11.1 
Clinical Data Management ............................................................................... 54 
11.2 
Completing and Signing Case Report Forms ................................................... 54 
11.3 
Data Quality Assurance .................................................................................... 54 
11.4 
Record Retention .............................................................................................. 55 
12 
STATISTICAL METHODS AND PLANNED ANALYSIS ...................................... 56 
12.1 
General Statistical Considerations .................................................................... 56 
12.2 
Populations for Analysis ................................................................................... 56 
12.3 
Subject Demographics/Other Baseline Characteristics .................................... 56 
12.4 
Study Treatments .............................................................................................. 57 
12.5 
Primary Efficacy Analysis ................................................................................ 57 
12.5.1 
Primary Efficacy Analyses ............................................................. 57 
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12.5.2 
Statistical Hypothesis and Method of Analysis .............................. 57 
12.5.3 
Handling of Missing Values/Censoring/Discontinuations ............. 57 
12.5.4 
Handling of Uninterpretable Images .............................................. 58 
12.6 
Secondary Efficacy Analyses ........................................................................... 58 
12.6.1 
Reader Assessment of Image Quality ............................................. 58 
12.6.2 
Reader Confidence in Striatal Visualization .................................. 58 
12.6.3 
Inter-Reader Agreement ................................................................. 58 
12.6.4 
Intra-Reader Reproducibility (Part 2 Only) .................................... 58 
12.7 
12.8 
Secondary Safety Analyses .............................................................................. 59 
12.8.1 
Secondary Safety Variables and Analyses ..................................... 59 
12.8.2 
Adverse Events ............................................................................... 59 
12.8.3 
Clinical Laboratory Evaluation ...................................................... 59 
12.8.4 
Vital Signs ...................................................................................... 60 
12.8.5 
Electrocardiograms ......................................................................... 60 
12.8.6 
Limited Physical Examination ....................................................... 61 
12.9 
Subgroup Analyses ........................................................................................... 61 
12.10 Interim Analysis ............................................................................................... 61 
12.11 Sample Size Calculation ................................................................................... 61 
12.12 Procedures for Missing, Unused and Spurious Data ........................................ 61 
12.13 Rules for Excluding Subjects from Analysis .................................................... 62 
12.14 Procedures for Reporting Deviations from Original Statistical Plan ............... 62 
13 
SPECIAL REQUIREMENTS AND PROCEDURES ................................................. 63 
13.1 
Regulatory and Ethical Considerations ............................................................ 63 
13.2 
Investigator’s Responsibilities .......................................................................... 63 
13.2.1 
Overall Responsibilities .................................................................. 63 
13.2.2 
Subject Informed Consent .............................................................. 64 
13.2.3 
Source Data/Documents ................................................................. 64 
13.2.4 
Confidentiality Regarding Study Subjects ..................................... 65 
13.2.5 
Data Protection ............................................................................... 65 
13.2.6 
Dissemination of Clinical Study Data ............................................ 65 
13.3 
Protocol Deviations .......................................................................................... 65 
13.4 
Study Monitoring .............................................................................................. 66 
13.5 
Audit and Inspection ......................................................................................... 66 
13.6 
Financial Disclosure ......................................................................................... 66 
13.7 
Insurance ........................................................................................................... 66 
13.8 
Publication Policy ............................................................................................. 66 
14 
REFERENCES ............................................................................................................. 68 
15 
APPENDICES .............................................................................................................. 70 
15.1 
Information on Investigational and Registered Products ................................. 70 
15.2 
Normal Limits for Vital Signs and ECG Intervals ........................................... 70 
16 
CLINICAL PROTOCOL AMENDMENT SUMMARIES .......................................... 71 
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16.1 
Amendment A01 .............................................................................................. 71 
16.1.1 
Reasons for Amendment ................................................................ 71 
16.1.2 
Description of Changes .................................................................. 71 
16.2 
Amendment A02 .............................................................................................. 76 
16.2.1 
Reasons for Amendment ................................................................ 76 
16.2.2 
Description of Changes .................................................................. 77 
2.2 
List of Tables 
Table 1 
Concomitant Medication List ................................................................................... 33 
Table 2 
Study Schedule of Events ......................................................................................... 37 
Table 3 
Clinical Laboratory Parameters ................................................................................ 43 
Table 4 
Criteria for Normal Limits for Vital Signs ............................................................... 70 
Table 5 
Criteria for Normal Limits for ECGs ....................................................................... 70 
2.3 
List of Figures 
Figure 1 
Overall 2-Part Study Diagram .................................................................................. 20 
Figure 2 
Subject Study Procedures ......................................................................................... 21 
Figure 3 
Figure 4 
Normal DAT SPECT Image ..................................................................................... 22 
Figure 5 
Partial Loss of Activity in Striata, with Greater Loss on the Left Side .................... 22 
Figure 6 
Complete Loss of Striatal Activity on the Left Side and Near Complete Loss on 
the Right Side ........................................................................................................... 23 
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3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation/Term 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse event 
Altropane (123I) Injection 
Drug product; referred to as Altropane in this protocol 
BIE 
Blinded Image Evaluation 
BP 
Blood pressure 
CIOMS 
Council for International Organizations of Medical Sciences 
CRF 
Case report form 
CRO 
Contract research organization 
DAT 
Dopamine transporter 
dPS 
Degenerative Parkinsonian Syndrome(s) 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
hCG 
Human chorionic gonadotropin 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation (formerly International 
Conference on Harmonisation) 
IMP 
Investigational medicinal product 
IRB 
Institutional/Independent Review Board 
IV 
Intravenous 
PD 
Parkinson’s Disease 
PS 
Parkinsonian syndrome(s) 
SAE 
Serious adverse event 
SBR 
Striatal binding ratio 
SOP 
Standard operating procedure 
SPECT 
Single photon emission computed tomography 
UTI 
Urinary tract infection 
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4 
BACKGROUND INFORMATION 
Movement disorders are common in elderly adults, yet arriving at a specific diagnosis can be 
difficult even for movement disorder experts [Abdo et al. 2010]. A subgroup of movement 
disorders includes the Parkinsonian syndromes (PS; also called Parkinsonism), of which the 
most common type is Parkinson’s disease (PD) [Abdo et al. 2010]. A PS is a clinical syndrome 
that includes bradykinesia in combination with rest tremor, rigidity, or both [Postuma et al. 
2015]. PS are very common in people aged 65 and older, ranging from 15% in the 65-to-74 
year age group to 52% in people aged 85 years and older [Bennett et al. 1996].  
Some types of PS, such as PD, are neurodegenerative, i.e., they involve nigrostriatal 
neurodegeneration, an irreversible loss of dopaminergic nigrostriatal neurons, which is 
responsible for the symptoms and signs in these disorders [Fahn 2003]. In evaluating patients 
with suspected PS, it is therefore helpful to differentiate between neurodegenerative PS (PD, 
progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and others) 
and non-neurodegenerative PS and other movement disorders (drug-induced PS, psychogenic 
PS, mimics of PS [such as depression, obsessive slowness, spasticity, dystonic tremor, frozen 
shoulder, slowing due to normal aging, and catatonia], and essential tremor) [Abdo et al. 2010]. 
In neurodegenerative PS, the reduction in nigrostriatal neurons is accompanied by a reduction 
in the presynaptic membrane expression of the dopamine transporter (DAT) protein. DAT 
facilitates dopamine removal from the synapse and its re-uptake into presynaptic nerve 
endings. Along with the reduction in DAT, there is a decrease in dopamine concentration. 
Thus, DAT can be considered a surrogate marker for the integrity of the nigrostriatal neuron 
bundle [Bannon et al. 2005].  
Based on evidence from human autopsies and a non-human primate model of PD, it is believed 
that a loss of at least 30% to 60% of nigrostriatal neurons must occur before symptoms begin 
[Bezard et al. 2001]. Once symptoms do begin, the degree of DAT loss is directly associated 
with the severity of symptoms [Ma et al. 1997]. 
The ability to visualize striatal DAT (or its loss) during life using diagnostic imaging is a 
valuable adjunct to clinical examination of patients with suspected Parkinsonian symptoms. 
The development of radiolabeled tropane derivatives with high binding affinity for the DAT, 
such as [123I]ioflupane (also known as [123I]FP-CIT and marketed as DaTscan® by GE 
HealthCare), [99mTc]TRODAT-1, [123I]β-CIT, and [123I]altropane, which act as functional 
tracers for DAT, make it possible to use single photon emission computed tomography 
(SPECT) imaging to visualize the distribution and density of nigrostriatal DAT [Brooks 2010] 
[Kung et al. 2007] [Marshall et al. 2009]. Indeed, DAT loss, as reflected by decreased striatal 
uptake of the radioligand, has been seen in the earliest clinical presentations of idiopathic PD 
and increases with the duration and severity of the disease [Chou et al. 2004] [Marshall and 
Grosset 2003].  
Although DAT imaging does not distinguish PD from other neurodegenerative PS, a normal 
DAT SPECT image does rule out nigrostriatal degeneration as a cause of the patient’s 
movement disorder. Thus, it would suggest an alternate diagnosis (such as essential tremor) 
that does not involve nigrostriatal neurodegeneration. Accurate diagnosis is important because 
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it affects disease management decisions. One meta-analysis showed that the use of 
[123I]ioflupane for SPECT imaging of the DAT in suspected cases of PS led to a change in 
management for 54% of patients [Bega et al. 2021]. 
[123I]β-CIT is a SPECT DAT imaging agent commonly used in clinical research. It has slow 
brain uptake kinetics and must be administered 24 hours before imaging [Bega et al. 2021]. 
[123I]Ioflupane is the only DAT tracer currently approved for use in the European Union (where 
it is marketed as DaTSCAN) and in the United States and Canada (where it is marketed as 
DaTscan®). Its brain uptake kinetics are faster than those of [123I]β-CIT, but it still must be 
administered 3 to 6 hours before imaging, limiting the timing and number of procedures at an 
imaging center. A tracer with even faster kinetics would be preferable for patient convenience 
and improved delivery of care.  
One such tracer is Altropane (123I) Injection (hereafter referred to as Altropane). It is being 
developed by GE HealthCare as a striatal SPECT imaging agent as an alternative to DaTscan. 
An important potential advantage of Altropane over DaTscan is the rapid uptake of the 
molecule resulting in significantly decreased time from injection to imaging (15 minutes with 
Altropane [Seibyl and Marek 2007] [Seibyl et al. 2008] vs. 3 to 6 hours with DaTscan 
[DaTscan Package Insert]). In addition, Altropane requires only 30 minutes of time in the 
scanner [Seibyl and Marek 2007] compared to the need to acquire 1.5 million counts for 
DaTscan (approximately 45 minutes) [DaTscan Package Insert]. 
To date, 10 clinical investigations of Altropane have been completed. These include 3 Phase 1 
studies, 4 Phase 2 studies, and 3 Phase 3 studies (for more details, please refer to the Altropane 
Investigator’s Brochure). These prior studies indicated that an 8-mCi dose of Altropane would 
be appropriate for clinical use. However, the question arose whether a 5-mCi dose (closer to 
the approved dose range of 3 to 5 mCi for DaTscan) would also be acceptable.  
This is a dose-evaluation study to determine if a 5-mCi Altropane dose would be acceptable for 
subsequent clinical studies including a Phase 3 study. This study has 2 parts: Part 1, which will 
definitely be conducted, and Part 2, which will only be conducted if Part 1 shows the 5-mCi 
dose to be acceptable.  
In Part 1, subjects with known normal striatal uptake on DaTscan images obtained within 1 
year (preferably within 6 months) before study enrollment and who have a clinical diagnosis 
(made by a movement disorder expert) that is consistent with the DaTscan images will undergo 
striatal SPECT imaging following intravenous (IV) administration of 5 mCi of Altropane. In a 
blinded image evaluation (BIE), 5 trained expert blinded readers will interpret, in random 
order, the Altropane 5-mCi images collected in this study along with normal and abnormal 8-
mCi Altropane images collected in prior studies; the 8-mCi images will be included to reduce 
the potential for bias if the blinded readers read only normal images. Endpoints that will be 
evaluated visually in the BIE are striatal visualization, reader confidence in striatal 
visualization, and image quality. Inter-reader agreement will be determined. The value of 
quantitative image data (striatal binding ratios [SBRs]) will be explored as well. If the 5-mCi 
dose of Altropane is found to be acceptable in Part 1, then Part 2 will be initiated; otherwise, 
the study will end after Part 1 and the 8-mCi dose will be selected for subsequent clinical 
studies. If Part 2 is conducted, then an additional endpoint will be intra-reader reproducibility.  
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5 
STUDY OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
The primary and secondary objectives of the study are as follows: 
Primary: 
•
To determine whether a 5-mCi dose of Altropane is acceptable for visualizing the right
and left striata.
The results will be used in deciding whether a 5-mCi or an 8-mCi dose will be recommended 
for subsequent clinical studies. The decision will be based first on whether a 5-mCi dose of 
Altropane is acceptable to visualize the striata in subjects with normal striatal uptake. If it is 
acceptable, then it will be additionally determined whether a 5-mCi dose of Altropane is 
acceptable to visualize the striata in subjects with abnormal striatal uptake (subjects with 
confirmed degenerative PS [dPS]).  
Secondary: 
•
To evaluate the safety of Altropane (using the endpoints adverse event [AE] and serious
AE [SAE] frequency, and changes from baseline in vital signs, physical examination,
electrocardiogram [ECG], and laboratory parameters).
5.2 
Study Endpoints 
5.2.1 
Study Endpoints for Part 1 
5.2.1.1 
Part 1 Primary Efficacy Endpoint 
•
Striatal visualization, reported as a forced choice of either normal (caudate and
putamen fully visible on left and right, or with small insignificant defects) or abnormal
(unilateral or bilateral reduced) striatal uptake.
5.2.1.2 
Part 1 Secondary Efficacy Endpoints 
•
Reader confidence in striatal visualization
•
Reader assessment of image quality
•
Inter-reader agreement
5.2.1.3 
Part 1 Secondary Safety Endpoints 
•
Subjects reporting 1 or more AE
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•
Adverse drug reaction (ADR) frequency
•
Changes from baseline in vital signs, physical examination, ECG, or laboratory
parameters
5.2.1.4 
5.2.2 
Study Endpoints for Part 2 (If applicable) 
5.2.2.1 
Part 2 Primary Efficacy Endpoint 
•
Striatal visualization, reported as a forced choice of either normal (caudate and
putamen fully visible on left and right, or with small insignificant defects) or abnormal
(unilateral or bilateral reduced) striatal uptake.
5.2.2.2 
Part 2 Secondary Efficacy Endpoints 
•
Reader confidence in striatal visualization
•
Reader assessment of image quality
•
Inter-reader agreement
•
Intra-reader reproducibility (including the images from Part 1)
5.2.2.3 
Part 2 Secondary Safety Endpoints 
•
Subjects reporting 1 or more AE
•
ADR frequency
•
Changes from baseline in vital signs, physical examination, ECG, or laboratory
parameters
5.2.2.4 
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6 
STUDY DESIGN 
6.1 
Overall Study Design and Plan 
Altropane is a diagnostic radiopharmaceutical under development for striatal DAT 
visualization using SPECT brain imaging, to assist in the evaluation of adult patients with 
suspected PS. Data from a prior clinical study show that an 8-mCi (296-MBq) Altropane dose 
provides images of diagnostic quality in patients with suspected PS. This open-label Phase 2 
dose evaluation study will determine if a 5-mCi (185-MBq) dose would also result in 
diagnostic-quality images. The study will evaluate a 5-mCi dose in up to 2 groups of subjects, 
in up to 2 parts.  
In Part 1, consenting subjects who have a DaTscan image showing normal striatal uptake and 
who have a consistent clinical diagnosis will be scheduled to undergo striatal SPECT with 5 
mCi of Altropane administered intravenously. If the visual interpretation of the striatal images 
of these subjects is concluded not to be acceptable, then Part 2 will not be conducted, the study 
will end, and the 8-mCi dose will be selected for further clinical development. However, if the 
visual interpretation is acceptable, then the study will proceed to Part 2. 
In Part 2, consenting subjects who have a DaTscan image showing abnormal striatal uptake 
and who have a consistent clinical diagnosis (dPS) will be scheduled to undergo striatal SPECT 
with 5 mCi of Altropane administered intravenously. If the visual interpretation of the striatal 
images from the dPS subjects is not acceptable, then the 8-mCi dose will be selected. However, 
if the visual interpretation is acceptable, then the 5-mCi dose will be selected. Figure 1 presents 
an overview of the 2-part study design and Figure 2 presents an overview of study procedures. 
At least 10 subjects with normal striatal uptake on DaTscan images will be recruited in Part 1. 
If Part 2 proceeds (dependent on the results of Part 1), then additionally at least 20 subjects 
with abnormal striatal uptake on DaTscan images (dPS subjects) will be recruited. Thus, the 
total number of subjects will be at least 10, or, if Part 2 is conducted, at least 30. Up to 5 
centers in the United States will be utilized for the study. 
Altropane SPECT images will be acquired for 30 minutes starting 15 to 20 minutes after 
dosing. Safety will be monitored continuously throughout the study and at a 24-hour follow-up 
telephone call after Altropane imaging. The anticipated effective radiation dose of Altropane 
from a 5-mCi dose is 4.09 mSv. 
Visual interpretation of the Altropane SPECT images will be conducted by 5 independent 
expert readers who are blinded to each subject’s clinical information, and who are not 
otherwise involved in the study. Their visual image interpretations will be a forced choice 
between normal (caudate and putamen fully visible on left and right, or with small insignificant 
defects) or abnormal (unilateral or bilateral reduced) striatal uptake. Readers will also evaluate 
their confidence in striatal visualization, rating it as high, medium, or low, and will assess 
image quality (as excellent, good, fair, poor, or unevaluable). 
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The dose selection decision will be based on consideration of all of the available data acquired 
within the study.  
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Figure 1 Overall 2-Part Study Diagram 
Dx=diagnosis;  PS = Parkinsonian syndrome 
The conduct of Part 2 is dependent on the results of Part 1. 
Choose 8-mCi
dose and stop 
study
Part 2
20 subjects with known abnormal
striatal uptake on DaTscan images
and consistent clinical Dx of
degenerative PS
Is 5-mCi dose
acceptable?
Image with 5-
mCi dose of
Altropane
No
Yes
Yes
Choose 8-mCi
dose
Part 1
10 subjects with known normal
striatal uptake on DaTscan images
and consistent clinical Dx
Image with 5-
mCi dose of
Altropane
Is 5-mCi dose
acceptable?
Start
No
Choose 5-mCi
dose
Blinded image
evaluation
Blinded image
evaluation
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Figure 2 Subject Study Procedures 
6.2 
Scientific Rationale for Study Design 
Altropane is an investigational DAT imaging agent that is under development for striatal DAT 
visualization using SPECT brain imaging to assist in the evaluation of adult patients with 
suspected PS. Its mechanism of action is similar to that of the approved agent DaTscan 
(ioflupane).  
DAT imaging agents bind reversibly with high affinity to the DAT protein, which is present on 
presynaptic dopaminergic nigrostriatal neurons. Radioactive decay of the attached tracer (I 123 
in the case of Altropane and ioflupane) releases photons that are suitable for imaging, allowing 
visualization of the striata.
Figure 3 
Visit 1: Screening 
(≤30 days prior to Visit 2) 
Visit 2: SPECT imaging 
(≤30 days after Visit 1) 
Administration of Altropane and imaging 
24-hour Safety Follow-Up Phone Call 
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In transaxial images, normal striatal DAT images are characterized by 2 symmetric comma- or 
crescent-shaped focal regions of activity mirrored about the median plane. Striatal activity is 
distinct relative to surrounding brain tissue. An example image, made using the DAT imaging 
agent DaTscan, is shown in Figure 4. 
Figure 4 Normal DAT SPECT Image 
Ref: [DaTscan Package Insert] 
Degenerative forms of PS such as PD result in loss of neurons, and concomitant loss of the 
DAT, which reduces binding of DAT imaging agents. Therefore, DAT SPECT images show 
reduced or absent activity where it would normally be expected. Depending on the extent of 
loss of nigrostriatal neurons, abnormal images may show partial (Figure 5) to complete (Figure 
6) loss of activity in the caudate and/or putamen.
Figure 5 Partial Loss of Activity in Striata, with Greater Loss on the Left Side 
Ref: [DaTscan Package Insert] 
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Figure 6 Complete Loss of Striatal Activity on the Left Side and Near Complete Loss on 
the Right Side 
Ref: [DaTscan Package Insert] 
From the above discussion, it should be evident that the dose of DAT imaging agent must be 
sufficient to completely visualize both striata when they are normal. Insufficient doses may 
result in incomplete visualization of either or both striata, which could result in a false-positive 
interpretation (i.e., apparent loss of activity in normal striatal uptake). Therefore, the first 
criterion for dose selection for a DAT imaging agent is acceptable visualization of normal 
striatal uptake.  
The second criterion is that the dose is able to visualize abnormal striatal uptake when there is 
at least some remaining DAT density. However, disease management depends on the 
normal/abnormal interpretation and not on the degree of abnormality, so as long as the dose 
results in the correct image classification (normal or abnormal) it is less important that it be 
able to categorize degrees of abnormality at this time.  
This study will evaluate a 5-mCi dose of Altropane for possible selection for Phase 3 instead of 
an 8-mCi dose. In accordance with the discussion above, it will first be determined (in Part 1) 
if a 5-mCi dose of Altropane results in acceptable visualization of normal striatal uptake. If it 
does not, then it would be unnecessary to test it in subjects with abnormal striatal uptake, in 
which case unnecessary exposure of subjects to radiation could be avoided.  
To avoid potential bias from having readers interpret only (or mostly) normal 5-mCi images in 
Part 1, some normal and abnormal Altropane images previously collected with 8-mCi doses 
will be included in random order in the BIE, and will serve as active control data. It should be 
noted, however, that the 8-mCi images will be from different subjects, so a direct intra-subject 
comparison of the 5-mCi and 8-mCi images will not be possible in this study.  
The design of this Phase 2 study supports the above aims and is consistent with standards 
typical for the study of a diagnostic imaging agent. The planned safety surveillance in this 
study is justifiable and adequate in view of the following: 
•
It permits within-subject comparison of safety variables pre- and post-administration of
Altropane.
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•
It allows a comparison of this study’s safety data set with similar data from other
studies.
•
The 24-hour follow-up for safety monitoring permits detection and evaluation of
late-appearing (or late-progressing) AEs.
•
The measures used to assess safety are well-defined and reliable, and the proposed
safety analyses are adequate to assess the effects of Altropane.
6.3 
Study Timeframe 
The study is expected to begin enrollment in 2Q 2023. The expected duration of each subject’s 
participation is up to approximately 32 days, with the precise duration dependent on the timing 
of the screening visit and the scheduling of study visits.  
6.4 
End of Study Definition 
The end of the study is defined as the date of the last visit/follow-up contact of the last subject 
in the study.  
6.5 
Risks and Benefits to Subjects 
All medical procedures carry some inherent risk. The known risks of Altropane administration 
include exposure to radiation, site injection effects (such as pain, redness, and or bruising), 
facial flushing, and headache. Other, as yet unknown, risks may be discovered with additional 
experience.  
Of 573 subjects administered Altropane in previous clinical trials, 206 subjects (36%) 
experienced at least 1 treatment-emergent AE. AEs considered by the investigator to be related 
to study drug were reported for 79 subjects (14%). One related AE (blood pressure increased) 
was considered severe; all others were considered to be mild or moderate in intensity, and most 
resolved within 24 hours. Headache was the most common ADR and was reported by 14 
subjects (2%). 
Four SAEs occurred: balance disorder, myocardial infarction, urinary tract infection (UTI), and 
transient ischemic attack. Of these events, only the UTI (of moderate intensity) was judged by 
the investigator to be possibly treatment related. GE HealthCare is unaware of a plausible 
mechanism by which Altropane could cause a UTI. No SAE was fatal. 
No clinically significant abnormalities in vital signs, laboratory parameters, ECG parameters, 
or physical or Mini-Mental State Examinations (MMSE®) were attributed to Altropane 
administration in previous clinical trials. 
Altropane is a radiopharmaceutical product and is therefore radioactive, emitting gamma 
radiation. Appropriate safety measures should be used when handling Altropane to avoid 
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unnecessary radiation exposure to the subject, occupational workers, clinical personnel, and 
other persons. Radiopharmaceuticals should be used by or under the control of physicians who 
are qualified by specific training and experience in the safe use and handling of radionuclides. 
Altropane contains the iodine radioisotope 123I; to prevent accumulation of 123I by the thyroid, 
thyroid blocking medication should be administered at least 1 hour ± 15 minutes before 
administration of Altropane, unless institutional practice dictates otherwise. 
It is recommended with the use of most radiopharmaceutical products to drink ample amounts 
of water and void frequently after the procedure and this is also recommended for Altropane. 
Altropane is an investigational drug product, meaning that it has not been approved by the 
Food and Drug Administration (FDA) to treat or diagnose a disease or syndrome. There is no 
anticipated direct benefit to the study subject from Altropane administration other than the 
opportunity to assist future patients who may receive the product for diagnostic purposes if it is 
approved by the FDA.  
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of Altropane may be found in the Investigator’s Brochure. 
Nonclinical Safety Studies of Altropane 
The nonclinical toxicology program included acute testing in rats and rabbits, single- and 
repeated-dose toxicity studies in Sprague Dawley rats, and 3 studies (including 2 in vitro 
studies and 1 in vivo study) designed to assess mutagenic potential. The non-radioactive form 
of the active ingredient of Altropane ([127I]-E-IACFT) did not result in any acute effects in rats 
or rabbits at a dose of 51 ng/kg (a human equivalent dose at least 35-fold higher, based on 
relative body surface areas, than the highest dosage of [123I]altropane considered for clinical 
use (9 mCi [approximately 16 ng]). In the 5-day repeated-dose study in rats, daily doses of 
6 µg/kg [127I]-E-IACFT for 5 consecutive days were well tolerated. This dosage, which is 
approximately 4000 times the highest dosage of Altropane considered for clinical use (9 mCi; 
16 ng), can be considered a no-observed adverse effect level dose. 
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7 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1 
Procedures for Enrollment 
In Part 1, subjects with normal striatal uptake on prior DaTscan images will be recruited at 
each study center. Potentially eligible subjects will be asked by study personnel about their 
willingness to participate in this study. 
Sites may identify subjects with abnormal striatal uptake (dPS subjects) for Part 2 but may not 
enroll them unless the decision is made by GE HealthCare to proceed with Part 2.  
7.2 
Inclusion Criteria 
Patients may be included in the study if they meet all of the following criteria: 
(1) 
For Part 1: a) the patient has a DaTscan image, obtained within 1 year (preferably 
within 6 months) before screening, that shows normal striatal uptake and b) the patient 
has a clinical diagnosis (made by a board-certified neurologist who is qualified by 
training and experience in the diagnosis of movement disorders) that is consistent with 
the DaTscan image.  
For Part 2 (if applicable): a) the patient has a DaTscan image, obtained within 1 year 
(preferably within 6 months) before screening, that shows abnormal (unilateral or 
bilateral reduced) striatal uptake and b) the patient also has a confirmed clinical 
diagnosis of a dPS (such as Parkinson’s disease, multiple system atrophy, corticobasal 
degeneration, progressive supranuclear palsy, etc.) made by a board-certified 
neurologist who is qualified by training and experience in the diagnosis of movement 
disorders, and c) the diagnosis is consistent with the DaTscan image. 
(2) 
The patient is male or female, ≥18 years of age, of any race and ethnicity. 
(3) 
The patient is able and willing to comply with study procedures and signed and dated 
informed consent is obtained.  
(4) 
If the patient is a woman of childbearing potential*, she must use a highly effective 
method of contraception** from Screening until 30 days after the last administration of 
Altropane, and the results of a serum or urine human chorionic gonadotropin (hCG) 
pregnancy test, performed at Screening and on the day of Altropane administration 
(with the result known before Altropane administration), must be negative.  
(5) 
If the patient is a male*** with a sexual partner who is a woman of childbearing 
potential*, he and his partner must use adequate contraception** from Screening until 
30 days after the last administration of Altropane.  
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* A woman of childbearing potential is neither post-menopausal nor surgically sterile. Post-menopausal means
having had no menses for at least 12 months without an alternative medical cause. Surgically sterile means having 
had a documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or any combination of these. 
** A highly effective method of contraception is one that has a failure rate of less than 1% per year when used 
consistently and correctly; such methods include combined (estrogen and progestogen containing) hormonal 
contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen-only 
hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine 
device; intrauterine hormone-releasing system; bilateral tubal ligation/occlusion; vasectomized partner (with 
medical confirmation of success); and abstinence from heterosexual intercourse involving a woman of 
childbearing potential.  
*** A male is considered fertile after puberty unless permanently sterile by bilateral orchidectomy, or 
vasectomized with confirmation of success. 
7.3 
Exclusion Criteria 
Patients must be excluded from participating in this study if they meet any of the following 
criteria: 
(1) 
The patient was previously included in this study. 
(2) 
Fewer than 7 disintegration half-lives have elapsed between the patient’s last procedure 
(therapeutic or diagnostic) involving a radioisotope and Visit 2 (altropane SPECT 
imaging). 
(3) 
Including participation in this study, the patient’s total exposure to radiation during 
medical procedures/tests in the past year would exceed 50 mSv. 
(4) 
The patient has participated in an investigational drug or device clinical trial within 30 
days before the date of informed consent. 
(5) 
The patient has any clinically significant or unstable physical or psychological illness, 
structural brain abnormality, abnormal laboratory results, or abnormal ECG (based on 
medical history or physical examination at Screening), as determined by the Principal 
Investigator, that would interfere with study participation. 
(6) 
The patient has any history of drug or alcohol abuse in the 2 years prior to the date of 
informed consent. 
(7) 
The patient has a positive urine screen for drugs of abuse at Screening. 
(8) 
The patient is a pregnant or breast-feeding female, or is a female of child-bearing 
potential that is not using appropriate birth control. 
(9) 
The patient is unable to lie supine for 1 hour. 
(10) 
The patient has any thyroid disease other than adequately treated hypothyroidism. 
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(11) 
The patient has known or suspected allergy/hypersensitivity to any ingredient in 
Altropane or to the thyroid blocking medication to be used before imaging. 
(12) 
The patient is currently taking any of the medications/treatments listed in the 
Concomitant Medication List (Table 1) as disallowed and cannot or will not discontinue 
use at least 12 hours prior to SPECT exam.  
(13) 
The patient was referred to DaTscan imaging for evaluation of possible cognitive 
impairment including dementia. 
7.4 
Screen Failures 
Screen failures are subjects who consent to participate in the clinical study but do not meet all 
inclusion and exclusion criteria within 30 days before Visit 2. Demographic and other data will 
be collected for all screen failures (see Section 9.1). Screen failures may be rescreened using 
their original screening number if there is a reasonable expectation that the reason(s) for the 
prior screen failure have resolved.  
7.5 
Withdrawal and Termination Criteria 
7.5.1 
Subject Withdrawal 
There are no formal withdrawal criteria for this study. During the conduct of the study, the 
Sponsor and Investigator 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 investigational medicinal 
product (IMP; i.e., Altropane), 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 evaluation at the time of the subject’s withdrawal 
should be made and an explanation given of why the subject is withdrawing or is being 
withdrawn from the study.  
The reason for withdrawal must be noted in the electronic case report form (eCRF). If the 
reason for withdrawal is an AE, monitoring will continue until the outcome is evident. The 
specific event or test result(s) must be recorded in the eCRF. 
To meet the study objectives, enrollment will continue to replace subjects who withdraw prior 
to completing SPECT scanning with Altropane.  
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7.5.2 
Subject Lost to Follow-Up 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
•
The site must attempt to contact the subject and reschedule the missed visit/follow-up
as soon as possible, counsel the subject on the importance of maintaining the assigned
visit schedule and ascertain whether or not the subject wishes to and/or should continue
in the study.
•
A subject will be considered lost to follow-up if he or she repeatedly fails to participate
in scheduled follow-up and cannot be contacted by the study site. Before a subject is
deemed lost to follow up, the investigator or designee must make every effort to regain
contact with the subject (where possible, 3 telephone calls and, if necessary, a certified
letter to the subject’s last known mailing address [or local equivalent methods]). These
contact attempts should be documented in the subject’s medical record.
•
Should the subject continue to be unreachable, he/she will be considered to have
withdrawn from the study.
7.5.3 
Study or Site Termination 
There are no formal termination criteria for this study. The Sponsor reserves the right to 
terminate the study or any site at any time for any reason. 
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8 
TREATMENT OF SUBJECTS 
8.1 
Investigational Medicinal Products 
8.1.1 
Investigational Medicinal Product: Altropane (123I) Injection 
Altropane, [123I]-2β-carbomethoxy-3β-(4-fluorophenyl)-N-((E)-3-iodoallyl) nortropane (also 
known as [123I]E-IACFT), will be provided as a sterile solution in a single-use vial as a 
formulation suitable for human IV administration. It contains excipients previously approved 
by the FDA for other IV products. Altropane is a clear, colorless solution. It should be stored at 
room temperature with appropriate radiation shielding. 
The drug substance (Altropane) is made with no carrier added. The molecular formula is 
C18H21FINO2. The anhydrous formula weight is 425 Da. The chemical mass of drug substance 
in a 5-mCi (185-MBq) dose is not more than 9 ng. The radioactive isotope of the drug 
substance, 123I, emits a 159-keV gamma ray which is readily detected by suitable SPECT 
cameras. The radioisotope has a disintegration half-life of 13.2 hours.  
Altropane will be manufactured and handled according to the applicable Good Manufacturing 
Practice at a qualified production facility. Before release, each batch of Altropane will be 
assessed by a number of quality control tests according to methods approved by the Sponsor. 
The batch produced must meet pre-specified criteria for color, clarity, radionuclidic identity 
and purity, radiochemical identity and purity, chemical purity, radioactive concentration, total 
vial radioactivity, pH, bacterial endotoxin level, and autoclave requirements. Results from 
sterility testing will not be available until after administration of Altropane. The final product 
will be formulated as a sterile solution for IV injection. All manufacturing, quality control 
testing, and documentation will be controlled and documented by the responsible person at the 
production site.  
Altropane is currently classified as a Schedule II controlled substance. The institution and/or 
relevant personnel must have a current Drug Enforcement Administration license for handling 
Schedule II substances. The site must also comply with the relevant FDA regulation (21 CFR 
312.69), which states, in part: 
“The investigator shall take adequate precautions, including storage of the 
investigational drug in a securely locked, substantially constructed cabinet, or other 
securely locked, substantially constructed enclosure, access to which is limited, to 
prevent theft or diversion of the substance into illegal channels of distribution.” 
Additional details of the chemical and pharmaceutical properties and formulation are described 
in the current Investigator’s Brochure. Sites will be provided with the Investigator’s Brochure 
for Altropane.  
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Administration of Altropane 
Altropane is a clear, colorless solution. When possible, the solution should be inspected 
visually for particulate matter and discoloration and not administered if either are seen.  
For administration of Altropane, access into a large peripheral vein (e.g., antecubital vein) 
should be established using a suitable IV catheter (22 gauge or larger diameter). To avoid 
extravasation of Altropane, correct localization of the catheter must be ensured by a test 
injection of normal saline prior to Altropane injection. 
Each subject will receive a single IV administration of 5 mCi (185 MBq) Altropane. The exact 
radioactive dose administered must be determined by calculating the difference between the 
radioactivity in the syringe and delivery system immediately before and after injection. After 
the dose is delivered, the syringe will be filled with a volume of saline equal to the 
administered dose volume and the syringe will be recounted under the same conditions as used 
to determine the dose; separately, the delivery system will be placed in a suitably sized plastic 
container and counted in the dose calibrator using the same parameters used for the dose. 
Measured radioactivity values, times of measurement, and total injected volume will be 
documented in the source documents and recorded in the eCRF. 
8.1.2 
Comparator 
There is no direct comparator in this study. 
8.1.3 
Adjunctive Product: Thyroid Blocking Medication 
Thyroid blocking medication (e.g., potassium iodide) will be administered orally at least 1 hour 
± 15 minutes before administration of Altropane, unless institutional protocols dictate 
otherwise. This should be recorded on the appropriate eCRF page.  
8.1.4 
Altropane Accountability 
Each investigator is responsible for ensuring that deliveries of Altropane and other study 
materials from the Sponsor are correctly received, recorded, handled, and stored safely and 
properly in accordance with all applicable regulatory guidelines (including those pertaining to 
radioactive products and Schedule II controlled substances), and used in accordance with this 
protocol. 
All Altropane containers (opened, unopened, or empty) must be destroyed on site after the 
study (following local institutional policies for disposal of hazardous waste), and after overall 
drug accountability has been completed by the Sponsor or representative. Radioactive 
containers, syringes, and delivery systems should be allowed to decay to background levels 
prior to disposal. See the Altropane handling procedures or similar document (e.g., Pharmacy 
Manual) for further details on receipt, recording, handling and accountability procedures 
related to Altropane. 
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A list of Altropane and other materials that were returned, or 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. 
8.1.5 
Registration of Product Complaints 
In the event of an Altropane complaint (e.g., breakage, leakage, particulate matter, 
discoloration), the investigator or recipient of Altropane is requested to report the problem on 
the shipping documentation (e.g., ‘Delivery Note for Product’, Drug Shipping and Receiving 
Form, or equivalent form). This should be promptly forwarded to the person indicated on the 
shipping documentation. The Responsible Person at the Sponsor 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. 
Lack of Efficacy: Any unusual/unexpected failure in diagnostic efficacy of Altropane should 
be reported by the investigator to the Sponsor immediately. The Sponsor will report unusual 
failure in efficacy of Altropane as required by regulatory authorities.  
8.2 
Method of Numbering Subjects 
A unique allocation number will be assigned to each subject at each center in successive order 
of entering the study after signing the informed consent form (ICF). No subject may be entered 
into the study more than once. The allocation number will be unique for each subject in the 
study and will consist of 7 digits in total: 3 digits for the center identification and 4 digits for 
the subject identification at the center (e.g., 002-0001: first subject in center No. 2). 
Once a subject number is assigned, it cannot be reassigned even if the subject is deemed 
ineligible or withdraws consent. To preserve the scientific integrity of the study, numbers must 
be assigned in numeric order.  
A subject who has given informed consent (or for whom informed consent has been given) but 
does not fulfil, within 30 days before Visit 2, the criteria to participate in the study will receive 
a subject number and will be logged as a screening failure. If the screen failure becomes 
eligible at a later time, the original number assigned for that subject will be used. 
The subject will also be documented on the Screening Log by using the subject’s initials 
(where permitted) and subject number.  
8.3 
Selection of Doses and Timing 
This is a dose-evaluation study. Each subject will undergo SPECT imaging with 5 mCi of 
Altropane.  The 5-mCi dose of Altropane was selected for the study because it is similar to the 
approved dose of DaTscan (3 to 5 mCi).  
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8.4 
Randomization and Blinding 
In this study, each subject will receive one 5-mCi dose of Altropane. No blinding of the 
Altropane will be performed.  
In the BIE, images will be presented in randomized order and readers will be blinded to clinical 
information, the identity of the tracer and tracer doses used to image subjects, and to this 
protocol. The BIE will be performed as described in Section 10.1 and the study Independent 
Review Charter. 
8.5 
Prior and Concomitant Medications or Procedures 
Any medications taken by the subject or medical procedures performed at Screening, 
Altropane administration, and up to the 24-hour safety follow-up after Visit 2 will be recorded 
in the eCRF along with the indication and dosage. Either the generic or the trade name may be 
recorded. The Sponsor/contract research organization (CRO) will encode all therapy and 
medication according to a current well-recognized dictionary of medical codes. 
8.5.1 
Prohibited Medications 
In accordance with Exclusion Criterion #12, subjects are not eligible for the study if they are 
currently taking any of the disallowed medications/treatments listed in the Concomitant 
Medication List (Table 1) and cannot or will not discontinue use at least 12 hours prior to the 
SPECT exam. 
Table 1 
Concomitant Medication List 
Allowed During Imaging: 
Disallowed During Imaging: 
Adrafinil 
Amantadine 
Amisulpride 
Apomorphine 
Benserazide 
Bromocriptine 
Cabergoline 
Carbidopa 
Citalopram 
Clozapine 
Deanxit 
Dihydroergotamine 
Domperidone 
Entacapone 
Escitalopram 
Haloperidol 
Levodopa 
Alpha methyldopa 
Amphetamine and its derivatives, including 
methamphetamine 
Benztropine 
Bupropion 
Ephedrine 
Methylphenidate 
Metoclopramide 
Modafinil 
Norephedrine 
Phentermine 
Reserpine 
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Table 1 
Concomitant Medication List 
Allowed During Imaging: 
Disallowed During Imaging: 
Lisuride 
Madopar 
Melperone 
Munuca pruriens (velvet bean) 
Olanzapine 
Paroxetine 
Pergolide 
Pramipexole 
Quetiapine 
Rasagiline 
Risperidone 
Ropinirole 
Rotigotine 
Safinamide 
Selegiline 
Sertraline 
Sinemet 
Stalevo 
Tiapride 
Tolcapone 
Venlafaxine 
Ziprasidone 
Ref: GE HealthCare Data on File 
8.6 
Contraception and Pregnancy Avoidance Procedure 
Altropane contains 123I, a source of gamma radiation that is potentially harmful to a fetus. 
Therefore, care should be taken to avoid enrolling women of childbearing potential who may 
be or plan to become pregnant, and to ensure that women of childbearing potential who enroll 
in the study do not become pregnant during the study. Therefore, if the subject is a woman of 
childbearing potential, she must use a highly effective method of contraception from Screening 
until 30 days after the administration of Altropane, and the results of a serum or urine hCG 
pregnancy test, performed at Screening and on the day of Altropane administration (with the 
result known before Altropane administration), must be negative. 
A woman of childbearing potential is neither post-menopausal nor surgically sterile. Post-
menopausal means having had no menses for at least 12 months without an alternative medical 
cause [CTFG Guidance 2020]. Surgically sterile means having had a documented 
hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or any combination of these. 
A highly effective method of contraception is one that has a failure rate of less than 1% per 
year when used consistently and correctly; such methods include combined (estrogen and 
progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, 
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intravaginal, or transdermal); progestogen-only hormonal contraception associated with 
inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine 
hormone-releasing system; bilateral tubal ligation/occlusion; vasectomized partner (with 
medical confirmation of success); and abstinence from heterosexual intercourse involving a 
woman of childbearing potential. 
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy, 
or vasectomized with confirmation of success.  
Subjects will be provided with information on acceptable methods of contraception as part of 
the subject informed consent process. Women of child-bearing potential must have a negative 
result for a urine or serum hCG pregnancy test at the time points detailed in Table 2. 
8.7 
Treatment Compliance 
Subjects will receive Altropane under direct supervision of study personnel. Each 
administration volume and the total radioactivity injected will be checked and the vial code and 
volume per administration will be recorded in each subject’s eCRF. Administered doses that 
are more than 10% outside of the target dose of 5 mCi must be reported as protocol deviations 
(see Section 13.3). 
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9 
STUDY PROCEDURES 
All efficacy and safety measurements obtained during the course of the study are summarized 
in the Study Schedule of Events (Table 2). 
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Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
Obtain written informed consent1 
X 
Assess and record inclusion and exclusion criteria 
X 
Record demographic information 
X 
Record medical/surgical history 
X 
Obtain clinical diagnosis provided by referring physician 
X 
Obtain most recent prior DaTscan images 
X 
Record prior/concomitant medications 
X 
Measure and record vital signs (temperature, heart rate, respiration rate, BP)3 
X 
X 
X 
Perform and record limited physical examination4
X 
X 
X 
Record 12-lead ECG5 
X 
X 
X 
Obtain blood samples for clinical laboratory tests (serum biochemistry and hematology)6
X 
X 
X 
Obtain urine drug screen for drugs of abuse 
X 
X 
Perform serum or urine hCG pregnancy test (women of childbearing potential only)7 
X 
X 
Inspect IV catheter site8 
X 
X 
Administer approved thyroid blocking medication orally at least 1 hour ± 15 minutes 
before Altropane injection unless institutional protocols dictate otherwise 
X 
Insert IV catheter (22 gauge or larger) 
X 
Draw Altropane into sterile syringe, measure activity 
X 
Administer Altropane via IV catheter 
X 
Measure residual activity in syringe and delivery system (immediately after injection); 
record administered activity 
X 
Perform SPECT imaging2 
X 
Monitor for adverse events/serious adverse events 
X 
X 
X 
BP = blood pressure; ECG = electrocardiogram; hCG = human chorionic gonadotropin; IV = intravenous; SPECT = single photon emission computed tomography 
1Must be obtained before any other screening is done.  
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Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
2Imaging should start 15 to 20 minutes after injection and last 30 minutes.  
3Vital signs determined at screening, within 3 hours before injection, and within 60 minutes after imaging. 
4Limited physical examination (assessment of general appearance, lungs and heart) at screening, within 3 hours before injection and within 60 minutes after imaging. 
512-Lead ECG obtained at screening, within 3 hours before injection, and within 60 minutes after imaging.  
6Blood samples are collected at screening, within 3 hours before injection, and within 60 minutes after imaging. 
7Women of childbearing potential must have a negative pregnancy test (serum or urine hCG) result at screening and within 3 hours before injection.  
8Inspect IV catheter site and record findings within 30 minutes before injection and within 60 minutes after imaging. 
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9.1 
Screening Visit (Visit 1) 
A Screening visit (Visit 1) will take place up to 30 days before the SPECT imaging visit (Visit 
2). Signed and dated informed consent must be obtained from all subjects prior to their entering 
the study and any screening procedures being performed. All subjects must satisfy all the 
inclusion criteria and none of the exclusion criteria listed in Sections 7.2 and 7.3. 
At the Screening visit, the following data will be obtained and recorded on the relevant pages 
of the eCRF: 
•
Inclusion and exclusion criteria
•
Demographic information
•
Medical/surgical history
•
Most recent prior DaTscan images (obtained within 1 year (preferably 6 months) before
screening) showing normal striatal uptake (Part 1) or abnormal striatal uptake (Part 2, if
applicable)
•
Baseline clinical diagnosis provided by the referring physician, which must be
consistent with the DaTscan images
•
Prior/concomitant medications
•
Vital signs (temperature, heart rate, respiration rate, blood pressure [BP]))
•
Limited physical examination (general appearance, lungs and heart)
•
12-lead ECG
•
Urine sample (for testing for drugs of abuse)
•
Blood for laboratory parameters (hematology and serum biochemistry)
•
Serum or urine hCG pregnancy test (for women of child-bearing potential)
•
AEs/SAEs
Waivers or protocol exceptions will not be granted by the Sponsor under any circumstances. 
Any exceptions to protocol-specified requirements will be considered as protocol deviations. 
9.2 
SPECT Imaging Visit (Visit 2) 
The Altropane SPECT Imaging Visit (Visit 2) will take place within 30 days after the 
Screening visit. If DaTscan imaging was conducted recently, the Altropane SPECT imaging 
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should occur at least 4 full days after the DaTscan imaging, to allow for elimination of 
DaTscan activity. 
The subject will be continuously monitored for the occurrence of AEs/SAEs during the visit. In 
addition, the following procedures will be performed, and the indicated data obtained and 
recorded, within the specified time windows: 
Within 3 hours before Altropane injection 
•
Limited physical examination (general appearance, lungs and heart)
•
Update prior/concomitant medications
•
Urine drug screen (for testing for drugs of abuse)
•
Vital signs (temperature, heart rate, respiration rate, BP)
•
12-lead ECG
•
Insert IV catheter (22 gauge or larger-diameter)
•
Serum or urine hCG pregnancy test (for women of child-bearing potential)
•
Blood sampling for serum biochemistry, hematology and pregnancy test (if opting
for serum test); may be done at the time of IV catheter insertion.
1 hour ± 15 minutes before injection 
•
Administer an approved thyroid blocking medication orally, unless institutional
protocols dictate other methods of thyroid blockade. Record on appropriate eCRF
page.
Within 30 minutes before injection 
•
Inspect IV catheter site and record findings
Subjects will be administered Altropane (5 mCi [185 MBq]) via the IV catheter, followed by a 
saline flush; the actual administered activity will be determined and recorded. SPECT imaging 
will be performed as detailed in the GE-278-001 Imaging Manual (Altropane). Imaging should 
start 15 to 20 minutes after Altropane injection and last for 30 minutes (the total time from 
injection until the end of imaging will be approximately 45 to 50 minutes).  
Within 60 minutes after imaging: 
•
Inspect IV catheter site and record findings
•
Update prior/concomitant medications
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•
Vital signs (temperature, heart rate, respiration rate, BP)
•
Limited physical examination (general appearance, lungs and heart)
•
12-lead ECG
•
Blood sampling for serum biochemistry and hematology
9.3 
24-hour Follow-Up (Visit 3) 
Subjects will be contacted by telephone 24 ± 6 hours after Visit 2 dosing, and AEs/SAEs and 
any changes in concomitant medications will be recorded. 
9.4 
Unscheduled Visits 
Unscheduled visits can be arranged at the discretion of the investigator. At a minimum, the 
date and reason for the visit will be captured. Any procedures performed will also be captured 
in the eCRF.  
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10 
EFFICACY, SAFETY, AND OTHER ASSESSMENTS 
10.1 
Efficacy Assessments 
Primary, secondary, and exploratory endpoints are provided in Section 5.2. 
10.1.1 
Image Acquisition 
Altropane SPECT images will be acquired for 30 minutes starting 15 to 20 minutes after 
injection. Further details of Altropane SPECT imaging requirements are provided in the GE-
278-001 Imaging Manual.  
10.1.2 
Image Interpretation and Correlation with Standard of Truth 
Altropane SPECT images will be visually interpreted by 5 expert blinded readers who are 
blinded to the Altropane dose as well as to each subject’s clinical information. Readers will 
interpret images independently of each other and will not be allowed to communicate with each 
other or be aware of any other reader’s findings. Caudate and putamen will be assessed 
individually in the left and right sides. Visual image interpretations will be a forced choice 
between normal (caudate and putamen fully visible on left and right, or with small insignificant 
defects) or abnormal (unilateral or bilateral reduced) striatal uptake.  
Readers will also rate their confidence in striatal visualization for the Altropane images as 
high, medium, or low, and evaluate image quality as excellent, good, fair, poor, or unevaluable. 
The BIE will be conducted in accordance with the study Independent Review Charter. 
10.2 
Safety Assessments 
The investigator(s) and the Sponsor/CRO will review the safety data. The following safety data 
will be collected and evaluated: 
•
Clinical laboratory parameters: serum biochemistry and hematology (Table 3).
•
Vital signs (temperature, heart rate, respiration rate, BP)
•
12-lead ECG (heart rate, PR interval, QRS interval, QT interval, QTc interval, notation
of abnormalities such as arrhythmias, infarct, etc.)
•
Limited physical examination (general appearance, lungs and heart)
•
AEs and SAEs
Pre-specified normal limits for vital signs and ECG intervals are provided in Section 15.2. 
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10.2.1 
Clinical Laboratory Evaluation 
Clinical laboratory parameters assessed in this study are displayed in Table 3. 
Table 3 
Clinical Laboratory Parameters 
Serum Biochemistry 
Hematology 
Urine Screenings 
•
Alanine aminotransferase
(ALAT)
•
Albumin
•
Alkaline phosphatase
•
Amylase
•
Aspartate aminotransferase
(ASAT)
•
Bicarbonate
•
Bilirubin (total, direct,
indirect)
•
Calcium
•
Chloride
•
Creatine phosphokinase
(CPK), total
•
Creatinine
•
Gamma-
glutamyltransferase (G-GT)
•
Glucose
•
Lactate dehydrogenase
•
Phosphorous
•
Potassium
•
Protein (total)
•
Sodium
•
Urea nitrogen
•
Uric acid
•
Red blood cell
(RBC) count
•
Platelet count
•
White blood cell
(WBC) count
Drugs of Abuse 
•
Amphetamine
•
Barbiturate
•
Benzodiazepine
•
Buprenorphine
•
Cocaine
•
Fentanyl
•
Tetrahydrocannabinol (THC)
•
3,4-methylenedioxymethamphetamine
(MDMA; “Molly”)
•
Methadone
•
Methamphetamine
•
Opiates
•
Oxycodone
•
Tricyclic Antidepressants
Pregnancy 
•
Human chorionic gonadotropin (hCG; unless
serum tested)
The signed and interpreted laboratory results will be kept at the site. 
Blood samples will be obtained for screening and for pre- and post-Altropane assessments of 
serum biochemistry and hematology parameters within the time point ranges described in 
Table 2. It is anticipated that the maximum amount of blood taken will not be more than 20 mL 
for all the samples taken during the subject’s study participation. Samples will be analyzed at a 
central clinical laboratory (for parameters, see Table 3).  
All blood samples will be processed and handled per standard laboratory procedures. All 
retained samples will be destroyed following institutional procedures after completion of the 
study. 
A urine screening for drugs of abuse will be performed at the time points described in Table 2; 
the drugs targeted by the drug screen are listed in Table 3.  
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 
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be followed up until the outcome is known. Also, additional diagnostic tests may be indicated 
to determine a more precise diagnosis of the subject’s condition (e.g., ordering a white blood 
cell differential to characterize a high or low white blood cell count, or ordering a 
determination of red cell indices to characterize a low hematocrit).  
10.2.2 
Vital Signs 
Vital signs (temperature, heart rate, respiration rate, BP) will be monitored at screening, and 
pre- and post-imaging, according to the study Schedule of Events (Table 2). Before vital signs 
are measured, the subject should rest for at least 5 minutes (if possible). The same position 
(e.g., seated) will be used each time vital signs are measured for a given subject, and blood 
pressure will be measured from the arm contralateral to the site of Altropane administration 
whenever possible. 
10.2.3 
Electrocardiograms 
A standard 12-lead ECG will be obtained at screening and at the pre- and post-imaging time 
points in Table 2. ECGs can be obtained on any local ECG machine. ECG clocks should be 
synchronized with imaging equipment. ECGs will be interpreted by the investigator or by a 
designee who is qualified by the institution to read ECGs and report the data at the 
investigative site.  Subject management decisions may be based on the 12-lead ECG findings. 
Each 12-lead ECG at each time point (and any derived data such as intervals and 
interpretations) must be identified with the subject’s initials and the subject’s study number, 
must show the date and time of recording, must be signed by the investigator with the date of 
his/her interpretation, and must be retained in the investigator’s study record for each subject. 
Any data required to be entered into the eCRF must be entered promptly.  
The investigator will not be expected to calculate QTc intervals. Pre-specified normal limits for 
12-lead ECG intervals that will be used by the Sponsor in data analysis are provided in 
Section 15.2. 
10.2.4 
Limited Physical Examination 
A qualified physician or a non-physician medically certified individual who is permitted by 
State/National law to perform physical examinations will conduct physical examinations 
according to the Schedule of Events (Table 2). Ideally, 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, lungs, and heart, and inspection of the IV catheter site before and after imaging. 
Abnormal injection site findings may include, but are not limited to: extravasation, bleeding, 
hematoma, redness, and infection. Abnormal injection site findings are to be recorded as AEs 
in the eCRF.  
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A new abnormal physical finding is one that occurs when a subject’s normal baseline physical 
examination becomes abnormal post-baseline. A worsening abnormal physical finding is one 
that was present at baseline (pre-dosing) that later becomes worse. New abnormal physical 
findings and worsening abnormal physical findings should be reported as AEs.  
10.2.5 
Adverse Events and Serious Adverse Events 
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 at least 30 minutes after tracer dosing. Treatment of SAEs should be primarily 
supportive of vital functions. 
10.2.5.1 
Definition of Adverse Event 
AE Definition: An AE is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An AE can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of an IMP, whether or not considered related to that 
product. 
Events Meeting the AE Definition 
•
Any abnormal laboratory test results (hematology, clinical biochemistry, or urinalysis)
or other safety assessments (e.g., ECG, vital-sign measurements), including those that
worsen from baseline, considered clinically significant in the medical and scientific
judgment of the investigator (i.e., not related to progression of underlying disease)
•
Exacerbation of a chronic or intermittent pre-existing condition including either an
increase in frequency and/or intensity of the condition
•
A new condition detected or diagnosed after IMP administration even though it may
have been present before the start of the study
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of IMP or a
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is
an intentional overdose taken with possible suicidal/self-harming intent. Such
overdoses should be reported regardless of sequelae.
Treatment-emergent AE: A treatment-emergent AE is an AE that begins or worsens between 
the start of IMP administration and the end of the follow-up period.   
Adverse Drug Reaction (ADR): An AE that is caused by the IMP. 
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Suspected Adverse Drug Reaction: An AE for which there is a reasonable possibility that the 
IMP caused the AE. “Suspected” implies a lesser degree of certainty about causality than 
adverse drug reaction.  
Serious Unexpected Suspected Adverse Drug Reaction: Any suspected ADR that is not in 
agreement with the Reference Safety Information, in nature or severity.  In this study the 
Reference Safety Information will be the Investigator’s Brochure. 
10.2.5.2 
Definition of Serious Adverse Event 
If an event is not an AE per the above definition, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a) Results in death
b) Is life-threatening
•
The term 'life-threatening' in the definition of 'serious' refers to an event in which the
subject was at risk of death at the time of the event.  It does not refer to an event, which
hypothetically might have caused death, if it were more severe.
c) Requires inpatient hospitalization or prolongation of existing hospitalization
•
In general, hospitalization signifies that the subject has been detained (usually involving
at least an overnight stay) at the hospital or emergency ward for observation and/or
treatment that would not have been appropriate in the physician’s office or outpatient
setting.  Complications that occur during hospitalization are AEs.  If a complication
prolongs hospitalization or fulfils any other serious criteria, the event is serious.  When
in doubt as to whether “hospitalization” occurred or was necessary, the AE should be
considered serious.
•
Hospitalization for elective treatment of a pre-existing condition that did not worsen
from baseline is not considered an AE.
d) Results in persistent disability/incapacity
•
The term disability means a substantial disruption of a person’s ability to conduct
normal life functions.
e) Is a congenital anomaly/birth defect
f)
Is another medically important event:
•
Medical or scientific judgment should be exercised in deciding whether SAE reporting
is appropriate in other situations, such as important medical events that may not be
immediately life-threatening or result in death or hospitalization but may jeopardize the
subject or may require medical or surgical intervention to prevent 1 of the other
outcomes listed in the above definition. These events should usually be considered
serious.
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•
Examples of such events include invasive or malignant cancers, intensive treatment in
an emergency room or at home for allergic bronchospasm, blood dyscrasias, or
convulsions that do not result in hospitalization, or development of drug dependency or
drug abuse.
Subjects will report all AEs to the investigator and/or qualified designee. 
10.2.5.3 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the 24-hour follow-up 
phone call at the time points specified in the Schedule of Events (Table 2). 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. The investigator will submit any updated SAE data 
to the Sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after conclusion of a subject’s 
study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and the investigator considers the 
event to be reasonably related to the IMP or study participation, then investigator must 
promptly notify the Sponsor. 
10.2.5.4 
Adverse Event and Serious Adverse Event Recording and Evaluation 
Adverse Event and Serious Adverse Event Recording: 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the IMP or study procedures, or that 
cause the subject to discontinue the study. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. 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. Open-ended and non-leading verbal questioning 
of the subject (e.g., “How do you feel?”) is the preferred method to inquire about 
AE occurrences. Subjects will be instructed to immediately report any symptoms and signs to 
the study staff (i.e., between formal observations). 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. The investigator will then record all relevant AE/SAE information in the 
eCRF and/or the SAE reporting form.  
It is not acceptable for the investigator to send photocopies of the subject’s medical records to 
the Sponsor/CRO in lieu of completion of the AE/SAE eCRF page/reporting form. However, 
there may be instances when copies of medical records for certain cases are requested by the 
Sponsor/CRO. In this case, all subject identifiers, with the exception of the subject number, 
will be redacted on the copies of the medical records before submission to the Sponsor/CRO. 
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The investigator will attempt to establish a diagnosis of the AE based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity (Severity): 
The investigator will make an assessment of the highest intensity for each AE and SAE 
reported during the study and assign it to 1 of the following categories:  
•
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and
not interfering with everyday activities.
•
Moderate: An event that causes sufficient discomfort and interferes with normal
everyday activities.
•
Severe: An event that prevents normal everyday activities. Note that a severe AE is not
the same as a Serious AE. Severe is a category utilized for rating the intensity of an
event; and both AEs and SAEs can be assessed as severe.
Assessment of Causality: 
The investigator is obligated to assess whether there is a reasonable possibility of a causal 
relationship between the IMP (Altropane) and each occurrence of each AE/SAE. A “reasonable 
possibility” of a relationship means that there are facts, evidence, and/or arguments to suggest a 
causal relationship, rather than a relationship cannot be ruled out. The investigator will use 
clinical judgment to assess the possibility of a causal relationship.  
Causality should be assessed as Related or Not related (Unrelated) to Altropane. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to IMP administration will be considered and 
investigated. The investigator will also consult the Investigator’s Brochure in his/her 
assessment to determine whether or not the AE was expected. 
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. Therefore, for each AE/SAE, the investigator must document in the medical 
notes that he/she has reviewed the AE/SAE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to the Sponsor/CRO.  However, it is very important 
that the investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor/CRO. 
The investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
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10.2.5.5 
Follow-Up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the 
event is otherwise explained, or the subject is lost to follow-up (as defined in Section 7.5.2).  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor/CRO 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation 
with other health care professionals. New or updated information will be recorded in the 
originally completed eCRF.  
The investigator will submit any updated SAE data to the Sponsor/CRO within 24 hours of 
receipt of the information. 
10.2.5.6 
Reporting Requirements for SAEs 
Prompt notification by the investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of an IMP 
under clinical investigation are met. Study centers are instructed to report all SAEs to the 
Sponsor/CRO within 24 hours.  
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of an IMP under clinical investigation. The Sponsor will 
comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional/Independent Review Boards (IRB), and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs or a MedWatch/Council for International 
Organizations of Medical Sciences [CIOMS]) from the sponsor will review and then file it in 
the site study file along with the Investigator’s Brochure and will notify the IRB if appropriate 
according to local requirements. 
SAE Reporting via an Electronic Data Collection Tool 
•
The primary mechanism for reporting an SAE to the Sponsor/CRO will be the
electronic data collection tool.
•
If the electronic system is unavailable, then the site will use the paper SAE data
collection tool (see next section) in order to report the event within 24 hours.
•
The site will enter the SAE data into the electronic system as soon as it becomes
available.
•
After the study is completed at a given site, the electronic data collection tool will be
taken off-line to prevent the entry of new data or changes to existing data.
•
If a site receives a report of a new SAE from a study subject or receives updated data on
a previously reported SAE after the electronic data collection tool has been taken off-
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line, then the site can report this information on a paper SAE form (see next section) or 
to the Sponsor/CRO by telephone. 
Contacts for SAE reporting are: 
Parties 
Email address 
Fax Number 
Phone Number 
GE HealthCare 
Pharmacovigilance 
SAE Reporting via Paper CRF 
•
Facsimile (fax) transmission or emailing of a scanned copy of the SAE paper case
report form (CRF) is the back-up method to transmit this information to the
Sponsor/CRO.
•
In rare circumstances and in the absence of facsimile/scanning equipment, notification
by telephone is acceptable with a copy of the SAE data collection tool sent by overnight
mail or courier service.
•
Initial notification via telephone does not replace the need for the investigator to
complete and sign the SAE CRF pages within the designated reporting time frames.
•
If an SAE is reported via paper CRF, the site will enter the SAE data into the electronic
system as soon as it becomes available.
An investigator who receives a safety report describing an SAE or other specific safety 
information (e.g., summary or listing of SAEs or a MedWatch/CIOMS) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the IRB, if 
appropriate according to local requirements. 
Emergency Contact Information 
Study sites are encouraged to provide subjects with study personnel contact information on 
wallet-sized cards informing them what to do in case of an emergency. In case of a clinical-
study related emergency, subjects should call 911 or study personnel, as appropriate to the 
situation.  
For any protocol or safety-related questions site personnel may contact: 
GE HealthCare Life Sciences 
251 Locke Drive, Marlborough, MA 01752 
Mobile: 
Email:
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10.2.6 
Urgent Safety Measures 
In accordance with the principles of Good Clinical Practice (GCP) as laid out in International 
Council for Harmonisation (ICH) E6, the investigator(s) has/have primary responsibility for 
assuring subject safety throughout the performance of study procedures. An urgent safety 
measure is any measure which an investigator may need to implement which is a deviation 
from, or a change in, the protocol to eliminate one or more immediate hazards to study subjects 
without prior IRB approval. 
The investigator may take appropriate urgent safety measures in order to protect the subjects of 
a clinical study 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 regulatory authority and the relevant IRB of the 
measures taken and the circumstances giving rise to those measures. 
All urgent safety measures must be reported to the Sponsor/CRO 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. 
10.2.7 
Pregnancy Reporting 
This process is aimed at ensuring the appropriate monitoring of the potential risk related to 
IMP exposure of pregnant women and/or fetuses 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. 
10.2.7.1 
Female Study Subjects 
Each female study subject must be advised by the investigator to inform him/her immediately 
if she suspects she may have become pregnant during the 30 days after IMP administration.  
When a female study subject reports a pregnancy that occurred within 30 days post-IMP 
administration, the investigator will arrange a confirmatory pregnancy test for her if the 
pregnancy has not been confirmed by another healthcare provider. The investigator will collect 
pregnancy information, record it on the appropriate form, and submit it to the sponsor within 
24 hours of learning of the subject’s pregnancy.  
The subject will be followed to determine the outcome of the pregnancy. The investigator will 
collect follow-up information on the subject 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 the estimated delivery date. Any termination of pregnancy will be reported, 
regardless of fetal status (presence or absence of anomalies) or indication for the procedure. 
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Any female subject who becomes pregnant while participating in the study will 
cancel/discontinue IMP administration and/or be withdrawn from the study. 
10.2.7.2 
Male Study Subjects 
Each male study subject must be advised by the investigator to inform him/her immediately if 
he suspects his partner may have become pregnant within 30 days after the subject was 
administered with the IMP.  
When a study subject reports a partner’s pregnancy that occurred within 30 days post-IMP 
administration, the investigator will attempt to obtain the partner’s informed consent for 
reporting the pregnancy, will arrange a pregnancy test for the study subject’s partner if the 
pregnancy has not been confirmed by another healthcare provider, and will attempt to collect 
and submit pregnancy information to the sponsor (within 24 hours of learning of the 
pregnancy.  
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. Generally, 
the follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure.  
10.2.7.3 
Pregnancy-Related Adverse Events 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE.  
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth (occurring 
at >22 weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy-related SAE considered reasonably related to the IMP by the 
investigator will be reported to the sponsor as described in Section 10.2.7. While the 
investigator is not obligated to actively seek this information in former study subjects, he or she 
may learn of an SAE through spontaneous reporting. 
10.3 
Other Variables 
10.3.1 
Demographic Data 
Subject demographic data (age, race, ethnicity, gender, weight, and height) will be recorded at 
Screening. Body mass index will be calculated from height and weight. 
10.3.2 
Medical and Surgical History 
Each subject’s relevant medical and surgical history will be recorded at Screening. 
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10.3.3 
Prior and Concomitant Medication 
Each subject’s prior/concomitant medications will be recorded at Screening, Visit 2, and the 
24-hour follow-up call (post-Visit 2). The thyroid blocking agent administered prior to 
Altropane SPECT should be recorded separately on the appropriate eCRF page.  
10.3.4 
Drug Screening 
A urine drug screen for drugs of abuse will be performed at Screening (Visit 1) and prior to 
imaging at Visit 2. Please refer to Table 2 for details.  
10.4 
Appropriateness of Measurements 
All assessments and measurements are appropriate and generally regarded as standard medical 
practice.  
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11 
DATA HANDLING AND QUALITY ASSURANCE 
11.1 
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. Full details of 
procedures for data handling will be documented in the Data Management Plan. 
11.2 
Completing and Signing Case Report Forms 
For electronic CRFs, data will be entered by trained site personnel with reasons given for any 
missing data. 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 
and the reason for the correction. The appropriate electronic signature will be provided. 
Any data recorded directly in the CRF, for which no other written or electronic record will be 
maintained in the subject’s medical record, will be considered source data and should be signed 
by the investigator(s) (e.g., results of physical examinations, vital-sign testing, or the IMP 
administration procedure). 
11.3 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic CRFs unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF. 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The investigator must permit study-related monitoring, audits, IRB review, and regulatory 
agency inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), 
methods, responsibilities and requirements, including handling of noncompliance issues and 
monitoring techniques (central, remote, or on-site monitoring) are provided in the Monitoring 
Plan.  
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
The Sponsor assumes accountability for actions delegated to other individuals (e.g., CROs). 
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Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of subjects are being protected; and that the study is being 
conducted in accordance with the currently approved protocol and any other study agreements, 
ICH GCP, and all applicable regulatory requirements. 
11.4 
Record Retention 
All study documentation at the investigator site and Sponsor site will be retained in accordance 
with ICH E6 GCP and the Sponsor/CRO’s quality standards and standard operating procedures 
(SOPs). 
All study records and documentation at the Investigator site and Sponsor site will be retained 
for a minimum of 15 years following study completion or discontinuation of the study, unless 
notified otherwise by the Sponsor or a longer period is required by local legislation.  The 
investigator must request written agreement from the Sponsor before destruction of archived 
study documentation. No records may be transferred to another location or party without 
written notification to the Sponsor. 
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12 
STATISTICAL METHODS AND PLANNED ANALYSIS 
The data will be analyzed 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. 
Data from participating centers in this protocol will be combined so that an adequate number of 
subjects will be available for analysis. The data will be summarized with respect to 
demographic and baseline characteristics, efficacy observations and measurements, and safety 
observations and measurements. 
12.1 
General Statistical Considerations 
Tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed using SAS software (Version 9.4 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 eCRF and entered into the database will 
be provided in separate data listings showing individual subject values. Summary tables and 
data listings will be presented overall, separated by clinical diagnosis at baseline and by study 
part (Part 1 and Part 2 [if applicable]). The planning and reporting of statistical analysis will be 
carried out as described in the Sponsor/CRO’s SOPs governing clinical studies and will be 
described in further detail in the Statistical Analysis Plan. 
12.2 
Populations for Analysis 
The Safety Analysis Set is defined as all subjects who receive any amount of Altropane. 
The Full Analysis Set is defined as all subjects who receive any amount of Altropane and have 
an Altropane image interpretation. 
For Part 1 the dose-evaluation (efficacy) analysis will be based on the Full Analysis Set. For 
Part 2 (if conducted) the dose-evaluation (efficacy) will also be based on the Full Analysis Set. 
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 Full Analysis Set.
•
Number of subjects included in the Safety Analysis Set.
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•
Number of subjects included in the dose-evaluation analysis set.
•
Number of subjects withdrawn from the study and the reason for withdrawal.
Demographic information (age, height, weight, and body mass index) will be summarized 
using descriptive statistics. Gender and race will be summarized by counts and percentages. 
Medical and surgical histories will be summarized by counts and percentages. Prior and 
concomitant medications will be recorded and coded using a standard classification system and 
grouped by primary and secondary classes, if applicable. 
12.4 
Study Treatments 
Administered doses of Altropane will be summarized by volume and radioactivity 
administered in Part 1 and, if applicable, in Part 2.  
The amount and type of medication used for thyroid blockade for each subject will also be 
summarized. 
12.5 
Primary Efficacy Analysis 
12.5.1 
Primary Efficacy Analyses 
•
Number and percentage of correct classifications of 5-mCi Altropane images from
subjects with normal striatal uptake (Part 1)
•
Number and percentage of correct classifications of 5-mCi Altropane images from
subjects with abnormal striatal uptake (Part 2, if applicable)
The correctness of image classification will be determined from the majority interpretation of 
the 5 expert blinded readers (at least 3 of 5 readers). 
12.5.2 
Statistical Hypothesis and Method of Analysis 
The 5-mCi dose will be considered to show acceptable striatal visualization if the percentage of 
correct majority classifications is greater than 70% in Part 1 and 75% in Part 2 (if applicable). 
12.5.3 
Handling of Missing Values/Censoring/Discontinuations 
The efficacy (dose-evaluation) analysis is based on the Full Analysis Set; all subjects in that 
analysis set will have an image. Other missing values will not be imputed, and only observed 
values will be used in data analyses and reports, unless otherwise specified in the Statistical 
Analysis Plan. 
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12.5.4 
Handling of Uninterpretable Images 
Not applicable. During the BIE the determination of striatal visibility will be forced so all 
images are considered 'interpretable' with respect to the primary objective. 
12.6 
Secondary Efficacy Analyses 
12.6.1 
Reader Assessment of Image Quality 
•
Number and percentage of Part 1 subjects with 5-mCi Altropane image quality judged
as excellent or good
•
Number and percentage of subjects in Part 2 (if applicable) with 5-mCi Altropane
image quality judged as excellent or good
The quality will be graded as excellent, good, fair, poor, or unevaluable. The results of this 
secondary analysis will be considered consistent with the results of the primary analysis if the 
percentage of images with excellent or good majority ratings is greater than 70%.  
12.6.2 
Reader Confidence in Striatal Visualization 
•
Number and percentage of Part 1 subjects with high confidence ratings for their 5-mCi
Altropane images
•
Number and percentage of Part 2 subjects (if applicable) with high confidence ratings
for their 5-mCi Altropane images
The confidence level will be graded as high, medium, or low. The results of this secondary 
analysis will be considered consistent with the results of the primary analysis if the percentage 
of images with high majority ratings of confidence is at least 70%.  
12.6.3 
Inter-Reader Agreement 
•
Number and percentage of images for which 5, 4, and 3 readers, respectively, are in
agreement on the subject classification for Part 1, and, if applicable, Part 2.
12.6.4 
Intra-Reader Reproducibility (Part 2 Only) 
•
Number and percentage of subjects for whom each reader's second image interpretation
agrees with his/her first image interpretation.
If Part 2 is conducted, each reader will read all images (including the images from Part 1) at 
least twice to determine intra-reader reproducibility. 
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12.7 
12.7.1 
12.8 
Secondary Safety Analyses 
The following sections apply to Part 1, and, if conducted, to Part 2. 
12.8.1 
Secondary Safety Variables and Analyses 
Safety analyses will be performed for treatment-emergent AEs, treatment-emergent SAEs, 
ADRs, serious ADRs, vital signs, physical examination, ECG, and laboratory tests.  
12.8.2 
Adverse Events 
AEs and SAEs will be coded using the Medical Dictionary for Regulatory Activities and all 
reported events will be listed for the Safety Analysis Set. The number and percentage of 
subjects with 1 or more treatment-emergent AEs will be summarized by system organ class and 
preferred term by Part 1 (and, if applicable, Part 2) and overall. Summaries will also be 
presented by AE intensity and judged relationship to IMP. Treatment-emergent SAEs will also 
be presented by Part 1 (and, if applicable, Part 2) and overall. Similar analyses will be 
performed for ADRs.  
12.8.3 
Clinical Laboratory Evaluation 
Descriptive statistics will be displayed for the observed values and changes from baseline in 
lab parameters. In addition, for each clinical laboratory variable and each time point, the 
following safety endpoints will be summarized by counts and percentages overall and by dose 
group: 
•
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 (Section 15.2)
(not applicable to qualitative parameters). Shift tables based on the normal range will be
prepared.
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12.8.4 
Vital Signs 
Descriptive statistics will be displayed for the observed values and changes from baseline in 
vital signs. For each vital-sign variable and each time point, the following safety endpoints will 
be summarized by counts and percentages overall and by dose group: 
•
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 BP, 10 mm Hg for
diastolic BP, 10 beats per minute for heart rate, 1.5oC for body temperature, or 10
breaths per minute for respiration rate).
•
The occurrence of post-administration values outside the normal limits (Section 15.2).
Shift tables based on the normal range will be prepared.
12.8.5 
Electrocardiograms 
Descriptive statistics will be displayed for the observed values and changes from baseline in 
ECG data. For each ECG variable and each time-point, the following safety endpoints will be 
summarized by counts and percentages overall and by dose group: 
•
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 15.2). Shift tables based on the normal range will be
prepared.
ECGs for which the overall interpretation was abnormal will be summarized overall and by 
dose group by counts and percentages at each post-administration time point. 
QTc correction: 
Two correction formulae will be employed in analyzing 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 
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12.8.6 
Limited 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 overall and by dose group. Shift tables will be prepared.  
12.9 
Subgroup Analyses 
Subgroup analyses by race, gender, and age category (e.g., <65 vs. ≥65) may be conducted as 
appropriate to the data.  
12.10 
Interim Analysis 
Results from Part 1 will be analyzed and based on the results a decision will be made whether 
or not to proceed to Part 2.  
12.11 
Sample Size Calculation 
Based on prior experience with an approved DAT imaging agent (DaTscan), it is expected that 
the probability of a correct subject classification based on Altropane images will be 92% in 
Part 1 and 91% in Part 2 (if it is conducted). 
In Part 1, 10 subjects with normal striatal uptake will be sufficient to determine whether or not 
the 5-mCi Altropane dose provides acceptable visualization of normal striatal uptake. Ten 
subjects with normal striatal uptake can achieve 62% power to detect whether the 5-mCi dose 
can result in a rate of correct subject classification of 70% or higher by a 1-sided exact test at a 
target significance level of 0.04. These results assume that the true rate of correct subject 
classification under the null hypothesis is 92% in Part 1.  
If Part 2 proceeds, then 20 subjects with abnormal striatal uptake will be sufficient to determine 
whether or not to proceed with the 5-mCi dose in Phase 3. Twenty subjects with abnormal 
striatal uptake will have 76% power to detect whether the 5-mCi dose can result in a rate of 
correct subject classification of 75% or higher under the assumption that the true rate of correct 
subject classification is 91%.  
12.12 
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.  
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12.13 
Rules for Excluding Subjects from Analysis 
Subjects will be included in the analysis sets as indicated in Section 12.2 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 a 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. 
12.14 
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 and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
•
Consensus ethical principles derived from international guidelines including the
Declaration of Helsinki and CIOMS International Ethical Guidelines
•
Applicable ICH GCP Guidelines
•
Applicable laws and regulations
Before starting this study, the protocol, ICF, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB and reviewed and approved by 
the IRB. The protocol will also be submitted to regulatory bodies/local health authorities in 
accordance with local regulations as required. The study will not start before the IRB gives 
written approval in accordance with ICH E6-GCP and all applicable regulatory bodies/local 
health authorities give approval as required. 
Any amendments to the protocol will require IRB approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study subjects (see Section 10.2.6). 
The investigator will be responsible for the following: 
•
Providing written summaries of the status of the study to the IRB annually or more
frequently in accordance with the requirements, policies, and procedures established by
the IRB
•
Notifying the IRB of SAEs or other significant safety findings as required by IRB
procedures
•
Providing oversight of the conduct of the study at the site and adherence to
requirements of 21 CFR, ICH guidelines, the IRB, and all other applicable local
regulations
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 
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regarding any investigational centers 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. The investigator or his/her representative will explain the nature of the 
study to the subject and/or his/her legally authorized representative and answer all questions 
regarding the study. 
Subjects must be informed that their participation is voluntary and 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.  
Subjects or their legally authorized representative will be required to sign and date a statement 
of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act requirements, where 
applicable, and the IRB or study center. Each subject’s signed ICF must be obtained before any 
procedures or assessments are done and after the aims, methods, anticipated benefits, potential 
hazards, and insurance arrangements in force are explained.  
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
The investigator(s) will keep the original consent forms. A copy of the signed ICF(s) must be 
provided to the subject or the subject’s legally authorized representative. 
Subjects who are rescreened are required to sign a new ICF. 
13.2.3 
Source Data/Documents 
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
The monitor(s), auditor(s), authorized personnel of the Sponsor/CRO, health authority 
inspector(s) or their agents, and authorized members of 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. 
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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 eCRFs 
and other documents or image material (including materials from all examinations, 
(e.g., SPECT 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 scrutinized for the purpose of verifying data recorded in 
the eCRF. This may be done by the monitor(s), properly authorized persons on behalf of the 
Sponsor, the quality assurance unit, or regulatory authorities. Personal medical information will 
always be treated as confidential. 
13.2.5 
Data Protection 
Subjects will be assigned a unique identifier by the sponsor. Any subject records or datasets 
that are transferred to the sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
The subject must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject who will be required to give consent for their data to be used as 
described in the informed consent.  
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB members, and by inspectors from regulatory authorities. 
13.2.6 
Dissemination of Clinical Study Data 
Clinical study results will be published on www.ClinicalTrials.gov. The results of this study 
may be published or presented at scientific meetings as described in Section 13.8.  
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 preventive 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 by the Sponsor under any circumstances. 
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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. 
13.6 
Financial Disclosure 
According to 21 CFR, Part 54, the Sponsor is required to completely and accurately disclose or 
certify to the FDA information concerning the financial interests of a clinical investigator (or 
investigating institution) who is not a full-time or part-time employee of the Sponsor. 
Therefore, the investigator(s) (or investigating institution) must provide the Sponsor with 
sufficient, accurate financial certification that none of the following financial arrangements 
(further defined in 21CFR Part 54.2) exist with the Sponsor or fully disclose the nature of the 
arrangement. This financial disclosure also applies to any financial arrangements that exist 
between the Sponsor and the investigator’s spouse(s) or dependent children: 
•
Compensation for participation in the study is affected by the outcome of the study.
•
Significant equity (greater than $50,000) interest in the Sponsor’s company.
•
Proprietary interest in the tested product.
•
Significant payments of other sorts, exceeding a monetary value of $25,000.
13.7 
Insurance 
This study is covered under the Sponsor’s Liability Insurance Policy. A Certificate of 
Insurance can be provided upon request. 
13.8 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before 
submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
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The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
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14 
REFERENCES 
[Abdo et al. 2010] 
Abdo WF, van de Warrenburg BPC, Burn DJ, et al. The clinical approach to movement 
disorders. Nat Rev Neurol. 2010;6(1):29-37.  
[Bannon et al. 2005] 
Bannon MJ. The dopamine transporter: role in neurotoxicity and human disease. Toxicology 
and Applied Pharmacology. 2005;204:355-60. 
[Bega et al. 2021] 
Bega D, Kuo PH, Chalkidou A, et al. Clinical utility of DaTscan in patients with suspected 
Parkinsonian syndrome: a systematic review and meta-analysis. NPJ Parkinsons Dis. 
2021;7(1):43. 
[Bennett et al. 1996] 
Bennett DA, Beckett LA, Murray AM, et al. Prevalence of parkinsonian signs and associated 
mortality in a community population of older people. N Engl J Med. 1996;334(2):71-6. 
[Bezard et al. 2001] 
Bezard E, Dovero S, Prunier C, et al. Relationship between the appearance of symptoms and 
the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine-lesioned macaque model of Parkinson's disease. J Neurosci. 
2001;21(17):6853-61. 
[Brooks 2010] 
Brooks DJ. Imaging approaches to Parkinson disease. Journal of nuclear medicine : official 
publication, Society of Nuclear Medicine 2010;51:596-609. 
[Chou et al. 2004] 
Chou KL, Hurtig HI, Stern MB, et al. Diagnostic accuracy of [99mTc]TRODAT-1 SPECT 
imaging in early Parkinson's disease. Parkinsonism Relat Disord. 2004;10:375-9. 
[CTFG Guidance 2020] 
Clinical Trial Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. Version 1.1. 2020. 
[DaTscan Package Insert] 
DaTscan™ Ioflupane I 123 Injection [package insert]. Arlington Heights, IL: GE Healthcare, 
Medi-Physics, Inc.; 2020. 
[Fahn 2003] 
Fahn S. Description of Parkinson’s disease as a clinical syndrome. Ann NY Acad Sci. 
2003;991:1-14. 
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[Gunther 1997] 
Günther I, Hall H, Halldin C, et al. [125I] beta-CIT-FE and [125I] beta-CIT-FP are superior to 
[125I] beta-CIT for dopamine transporter visualization: autoradiographic evaluation in the 
human brain. Nucl Med Biol. 1997 Oct;24(7):629-34.  
[Kung et al. 2007] 
Kung HF, Kung MP, Wey SP, et al. Clinical acceptance of a molecular imaging agent: a long 
march with [99mTc]TRODAT. Nuclear Medicine and Biology. 2007;34:787-9. 
[Ma et al. 1997] 
Ma SY, Roytta M, Rinne JO, et al. Correlation between neuromorphometry in the substantia 
nigra and clinical features in Parkinson’s disease using disector counts. J Neurol Sci. 
1997;151:83-7. 
[Marshall and Grosset 2003] 
Marshall V, Grosset D. Role of dopamine transporter imaging in routine clinical practice. Mov 
Disord. 2003;18:1415-23. 
[Marshall et al. 2009] 
Marshall VL, Reininger CB, Marquardt M, et al. Parkinson's disease is overdiagnosed 
clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study 
with repeat [123I]FP-CIT SPECT. Mov Disord. 2009;24:500-8. 
[Postuma et al. 2015] 
Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. 
Mov Disord. 2015;30(12):1591-601. 
[Seibyl and Marek 2007] 
Seibyl JP, Marek K. Optimizing the performance of ALTROPANE® SPECT imaging in 
Parkinson disease and control subjects: Phase II Clinical Report: Molecular NeuroImaging, 
LLC; 2007. 
[Seibyl et al. 2008] 
Seibyl J, Jennings D, Zubal G, Marek K. ALTROPANE SPECT in Parkinson’s disease patients 
and healthy controls (poster). Abstracts of The Movement Disorder Society's Twelfth 
International Congress of Parkinson's Disease and Movement Disorders: Movement Disorders; 
2008:Poster no. 194. 
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15 
APPENDICES 
15.1 
Information on Investigational and Registered Products 
The reference document for Altropane in this study is the Investigator’s Brochure for 
Altropane. The reference document provides up-to-date information on the efficacy and safety 
of Altropane, 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 
Normal Limits for Vital Signs and ECG Intervals 
Table 4 
Criteria for Normal Limits for Vital Signs 
Vital Sign Parameter 
Normal Limits
Low 
High 
Systolic BP (mmHg) 
85 
139 
Diastolic BP (mmHg) 
60 
89 
Heart Rate (bpm) 
60 
100 
Respiration Rate (rpm) 
12 
22 
Body Temperature 
36.4C (97.5F) 
37.7C (99.5F) 
Oxygen Saturation (%) 
93 
100 
Table 5 
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 
(gender not specified) 
- 
440 
QTc intervala
(gender not specified) 
- 
440 
a No lower boundary set for QTc. 
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16 
CLINICAL PROTOCOL AMENDMENT SUMMARIES 
16.1 
Amendment A01 
16.1.1 
Reasons for Amendment 
•
Typographical errors where the timing of some safety assessments were based on
timing of the Altropane injection were corrected to be based on the timing of the
imaging.
•
The start of study enrollment was updated to current expectations.
•
Minor typographical corrections.
•
GE Healthcare has been formatted to GE HealthCare throughout the protocol for
consistency with company branding following spin off. This minor formatting change is
not detailed further below.
Where appropriate, the changes documented below are also made in the synopsis. Where 
appropriate the changes are indicated in italics. 
16.1.2 
Description of Changes 
Section 6.3, Study Timeframe, first sentence 
Previously read: 
The study is expected to begin enrollment in 3Q 2022. 
Now reads: 
The study is expected to begin enrollment in 2Q 2023. 
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Section 9, Study Procedures, Table 2 (Study Schedule of Events) 
Previously read: 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
dosing) 
Pre-Imaging Imaging2 Post-Imaging 
Obtain written informed consent1 
X 
Assess and record inclusion and exclusion criteria 
X 
Record demographic information 
X 
Record medical/surgical history 
X 
Obtain clinical diagnosis (ET for Part 1; dPS for Part 2) provided by referring physician 
X 
Obtain most recent prior DaTscan images 
X 
Record prior/concomitant medications 
X 
Measure and record vital signs (temperature, heart rate, respiration rate, BP)3 
X 
X 
X 
Perform and record limited physical examination4
X 
X 
X 
Record 12-lead ECG 
X 
X 
X 
Obtain blood samples for clinical laboratory tests (serum biochemistry and hematology)5
X 
X 
X 
Obtain urine drug screen for drugs of abuse 
X 
X 
Perform serum or urine hCG pregnancy test (women of childbearing potential only)6 
X 
X 
Inspect IV catheter site7 
X 
X 
Administer approved thyroid blocking medication orally at least 1 hour ± 15 minutes 
before Altropane injection unless institutional protocols dictate otherwise 
X 
Insert IV catheter (22 gauge or larger) 
X 
Draw Altropane into sterile syringe, measure activity 
X 
Administer Altropane via IV catheter 
X 
Measure residual activity in syringe and delivery system (immediately after injection); 
record administered activity 
X 
Perform SPECT imaging2 
X 
Monitor for adverse events/serious adverse events 
X 
X 
X 
BP = blood pressure; dPS = Degenerative Parkinsonian Syndrome; ECG = electrocardiogram; ET = essential tremor; hCG = human chorionic gonadotropin; IV = 
intravenous; SPECT = single photon emission computed tomography 
1Must be obtained before any other screening is done.  
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Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
dosing) 
Pre-Imaging Imaging2 Post-Imaging 
2Imaging should start 15 to 20 minutes after injection and last 30 minutes.  
3Vital signs determined within 3 hours before injection and within 60 minutes after injection. 
4Limited physical examination (assessment of general appearance, lungs and heart) at screening, within 3 hours before and within 60 minutes after imaging. 
5Blood samples collected at screening, within 3 hours before Altropane injection, and within 60 minutes after injection. 
6Women of childbearing potential must have a negative pregnancy test (serum or urine hCG) result at screening and within 3 hours before radiopharmaceutical 
injection.  
7Inspect IV catheter site and record findings within 30 minutes before injection and within 60 minutes after imaging. 
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Now reads: 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
Obtain written informed consent1 
X 
Assess and record inclusion and exclusion criteria 
X 
Record demographic information 
X 
Record medical/surgical history 
X 
Obtain clinical diagnosis (ET for Part 1; dPS for Part 2) provided by referring physician 
X 
Obtain most recent prior DaTscan images 
X 
Record prior/concomitant medications 
X 
Measure and record vital signs (temperature, heart rate, respiration rate, BP)3 
X 
X 
X 
Perform and record limited physical examination4
X 
X 
X 
Record 12-lead ECG5 
X 
X 
X 
Obtain blood samples for clinical laboratory tests (serum biochemistry and hematology)6
X 
X 
X 
Obtain urine drug screen for drugs of abuse 
X 
X 
Perform serum or urine hCG pregnancy test (women of childbearing potential only)7 
X 
X 
Inspect IV catheter site8 
X 
X 
Administer approved thyroid blocking medication orally at least 1 hour ± 15 minutes 
before Altropane injection unless institutional protocols dictate otherwise 
X 
Insert IV catheter (22 gauge or larger) 
X 
Draw Altropane into sterile syringe, measure activity 
X 
Administer Altropane via IV catheter 
X 
Measure residual activity in syringe and delivery system (immediately after injection); 
record administered activity 
X 
Perform SPECT imaging2 
X 
Monitor for adverse events/serious adverse events 
X 
X 
X 
BP = blood pressure; dPS = Degenerative Parkinsonian Syndrome; ECG = electrocardiogram; ET = essential tremor; hCG = human chorionic gonadotropin; IV = 
intravenous; SPECT = single photon emission computed tomography 
1Must be obtained before any other screening is done.  
2Imaging should start 15 to 20 minutes after injection and last 30 minutes.  
3Vital signs determined at screening, within 3 hours before injection, and within 60 minutes after imaging. 
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Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
4Limited physical examination (assessment of general appearance, lungs and heart) at screening, within 3 hours before injection and within 60 minutes after imaging. 
512-Lead ECG obtained at screening, within 3 hours before injection, and within 60 minutes after imaging.  
6Blood samples collected at screening, within 3 hours before injection, and within 60 minutes after imaging. 
7Women of childbearing potential must have a negative pregnancy test (serum or urine hCG) result at screening and within 3 hours before injection.  
8Inspect IV catheter site and record findings within 30 minutes before injection and within 60 minutes after imaging. 
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Section 10.2.2, Vital Signs, First sentence 
Previously read: 
Vital signs (temperature, heart rate, respiration rate, BP) will be monitored at screening, and 
pre- and post-administration, according to the study Schedule of Events (Table 2). 
Now reads: 
Vital signs (temperature, heart rate, respiration rate, BP) will be monitored at screening, and 
pre- and post-imaging, according to the study Schedule of Events (Table 2). 
Section 10.2.3, Electrocardiograms, First sentence 
Previously read: 
A standard 12-lead ECG will be obtained at screening and at the pre- and post-administration 
time points in Table 2. 
Now reads: 
A standard 12-lead ECG will be obtained at screening and at the pre- and post-imaging time 
points in Table 2. 
16.2 
Amendment A02 
16.2.1 
Reasons for Amendment 
Feedback from the study sites has indicated that few patients with essential tremor undergo 
DaTscan imaging, and that, although there is a high proportion of DaTscan images that are 
negative (about 50% at one site), relatively few of these have essential tremor. As a result, 
enrollment has been slow in Part 1. Therefore, the protocol is being amended to allow patients 
with negative DaTscan images to be considered for Part 1 (provided they meet all other 
inclusion and exclusion criteria).  
Where appropriate, the changes documented below are also made in the synopsis. Where 
appropriate the changes are indicated in italics. In addition, minor typographical edits were 
made for clarity or as a result of these edits. 
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16.2.2 
Description of Changes 
Section 4, Background Information, Last Paragraph, First Sentence 
Previously read: 
In Part 1, subjects with known normal striatal uptake on DaTscan images obtained within 1 
year (preferably within 6 months) before study enrollment and who have a clinical diagnosis of 
ET will undergo striatal SPECT imaging following intravenous (IV) administration of 5 mCi of 
Altropane. 
Now reads: 
In Part 1, subjects with known normal striatal uptake on DaTscan images obtained within 1 
year (preferably within 6 months) before study enrollment and who have a clinical diagnosis 
(made by a movement disorder expert) that is consistent with the DaTscan images will undergo 
striatal SPECT imaging following intravenous (IV) administration of 5 mCi of Altropane. 
Section 5.1, Objectives, Primary Paragraph 
Previously read: 
The results will be used in deciding whether a 5-mCi or an 8-mCi dose will be recommended 
for subsequent clinical studies. The decision will be based first on whether a 5-mCi dose of 
Altropane is acceptable to visualize the striata in subjects with normal striatal uptake (who 
have confirmed ET). If it is acceptable, then it will be additionally determined whether a 5-mCi 
dose of Altropane is acceptable to visualize the striata in subjects with abnormal striatal uptake 
(subjects with confirmed degenerative PS [dPS]). 
Now reads: 
The results will be used in deciding whether a 5-mCi or an 8-mCi dose will be recommended 
for subsequent clinical studies. The decision will be based first on whether a 5-mCi dose of 
Altropane is acceptable to visualize the striata in subjects with normal striatal uptake. If it is 
acceptable, then it will be additionally determined whether a 5-mCi dose of Altropane is 
acceptable to visualize the striata in subjects with abnormal striatal uptake (subjects with 
confirmed degenerative PS [dPS]). 
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Section 6.1, Overall Study Design and Plan, 2nd and 4th Paragraphs 
Previously read: 
… 
In Part 1, consenting subjects who have a DaTscan image showing normal striatal uptake and 
who have a consistent clinical diagnosis (ET) will be scheduled to undergo striatal SPECT with 
5 mCi of Altropane administered intravenously. If the visual interpretation of the striatal 
images of these subjects is concluded not to be acceptable, then Part 2 will not be conducted, 
the study will end, and the 8-mCi dose will be selected for further clinical development. 
However, if the visual interpretation is  acceptable, then the study will proceed to Part 2. 
… 
At least 10 subjects with normal striatal uptake on DaTscan images (ET subjects) will be 
recruited in Part 1. If Part 2 proceeds (dependent on the results of Part 1), then additionally at 
least 20 subjects with abnormal striatal uptake on DaTscan images (dPS subjects) will be 
recruited. Thus, the total number of subjects will be at least 10, or, if Part 2 is conducted, at 
least 30. Up to 5 centers in the United States will be utilized for the study. 
… 
Now reads: 
… 
In Part 1, consenting subjects who have a DaTscan image showing normal striatal uptake and 
who have a consistent clinical diagnosis will be scheduled to undergo striatal SPECT with 5 
mCi of Altropane administered intravenously. If the visual interpretation of the striatal images 
of these subjects is concluded not to be acceptable, then Part 2 will not be conducted, the study 
will end, and the 8-mCi dose will be selected for further clinical development. However, if the 
visual interpretation is  acceptable, then the study will proceed to Part 2. 
… 
At least 10 subjects with normal striatal uptake on DaTscan images will be recruited in Part 1. 
If Part 2 proceeds (dependent on the results of Part 1), then additionally at least 20 subjects 
with abnormal striatal uptake on DaTscan images (dPS subjects) will be recruited. Thus, the 
total number of subjects will be at least 10, or, if Part 2 is conducted, at least 30. Up to 5 
centers in the United States will be utilized for the study. 
… 
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Page 79 of 88 
Section 6.1, Overall Study Design and Plan, Figure 1 
Previously read: 
Figure 1 Overall 2-Part Study Diagram 
Dx=diagnosis; ET = essential tremor; PS = Parkinsonian syndrome 
The conduct of Part 2 is dependent on the results of Part 1. 
Now reads: 
Figure 1 Overall 2-Part Study Diagram 
Dx=diagnosis; PS = Parkinsonian syndrome 
The conduct of Part 2 is dependent on the results of Part 1. 
Choose 8-mCi 
dose and stop 
study
Part 2
20 subjects with known abnormal
striatal uptake on DaTscan images 
and consistent clinical Dx of 
degenerative PS
Is 5-mCi dose 
acceptable?
Image with 5-
mCi dose of 
Altropane
No
Yes
Yes
Choose 8-mCi 
dose 
Part 1
10 subjects with known normal
striatal uptake on DaTscan 
images and clinical Dx of ET
Image with 5-
mCi dose of 
Altropane
Is 5-mCi dose 
acceptable?
Start
No
Choose 5-mCi 
dose
Blinded image 
evaluation
Blinded image 
evaluation
Choose 8-mCi
dose and stop 
study
Part 2
20 subjects with known abnormal
striatal uptake on DaTscan images
and consistent clinical Dx of
degenerative PS
Is 5-mCi dose
acceptable?
Image with 5-
mCi dose of
Altropane
No
Yes
Yes
Choose 8-mCi
dose
Part 1
10 subjects with known normal
striatal uptake on DaTscan images
and consistent clinical Dx
Image with 5-
mCi dose of
Altropane
Is 5-mCi dose
acceptable?
Start
No
Choose 5-mCi
dose
Blinded image
evaluation
Blinded image
evaluation
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023


GE HealthCare Confidential 
Page 80 of 88 
Section 7.1, Procedures for Enrollment, First Paragraph 
Previously read: 
In Part 1, subjects with normal striatal uptake (ET subjects) on prior DaTscan images will be 
recruited at each study center. Potentially eligible subjects will be asked by study personnel 
about their willingness to participate in this study. 
Now reads: 
In Part 1, subjects with normal striatal uptake on prior DaTscan images will be recruited at 
each study center. Potentially eligible subjects will be asked by study personnel about their 
willingness to participate in this study. 
Section 7.2, Inclusion Criteria #1 
Previously read: 
(1) 
For Part 1: a) the patient has a DaTscan image, obtained within 1 year (preferably 
within 6 months) before screening, that shows normal striatal uptake and b) the patient 
has a clinical diagnosis of ET made by a board-certified neurologist who is qualified by 
training and experience in the diagnosis of movement disorders, and c) the diagnosis is 
consistent with the DaTscan image.  
For Part 2 (if applicable): a) the patient has a DaTscan image, obtained within 1 year 
(preferably within 6 months) before screening, that shows abnormal (unilateral or 
bilateral reduced) striatal uptake and b) the patient also has a confirmed clinical 
diagnosis of a dPS (such as Parkinson’s disease, multiple system atrophy, corticobasal 
degeneration, progressive supranuclear palsy, etc.) made by a board-certified 
neurologist who is qualified by training and experience in the diagnosis of movement 
disorders, and c) the diagnosis is consistent with the DaTscan image. 
Now reads: 
(1) 
For Part 1: a) the patient has a DaTscan image, obtained within 1 year (preferably 
within 6 months) before screening, that shows normal striatal uptake and b) the patient 
has a clinical diagnosis (made by a board-certified neurologist who is qualified by 
training and experience in the diagnosis of movement disorders)that is consistent with 
the DaTscan image.  
For Part 2 (if applicable): a) the patient has a DaTscan image, obtained within 1 year 
(preferably within 6 months) before screening, that shows abnormal (unilateral or 
bilateral reduced) striatal uptake and b) the patient also has a confirmed clinical 
diagnosis of a dPS (such as Parkinson’s disease, multiple system atrophy, corticobasal 
degeneration, progressive supranuclear palsy, etc.) made by a board-certified 
GE-278-001 Clinical Protocol Amendment A02
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GE HealthCare Confidential 
Page 81 of 88 
neurologist who is qualified by training and experience in the diagnosis of movement 
disorders, and c) the diagnosis is consistent with the DaTscan image. 
Section 7.3, Exclusion Criteria #2 
Previously read: 
(2) 
The patient has had any exposure to radiopharmaceutical products within 30 days 
before the date of informed consent. 
Now reads: 
(2) 
Fewer than 7 disintegration half-lives have elapsed between the patient’s last 
procedure (therapeutic or diagnostic) involving a radioisotope and Visit 2 (altropane 
SPECT imaging). 
Section 7.3, Exclusion #13 (New Criteria) 
Now reads: 
(13) 
The patient was referred to DaTscan imaging for evaluation of possible cognitive 
impairment including dementia. 
Section 7.4, Screen Failures 
Previously read: 
Screen failures are subjects who consent to participate in the clinical study but do not meet all 
inclusion and exclusion criteria. Demographic and other data will be collected for all screen 
failures (see Section 9.1). Screen failures may be rescreened using their original screening 
number if there is a reasonable expectation that the reason(s) for the prior screen failure have 
resolved. 
Now reads: 
Screen failures are subjects who consent to participate in the clinical study but do not meet all 
inclusion and exclusion criteria within 30 days before Visit 2. Demographic and other data will 
be collected for all screen failures (see Section 9.1). Screen failures may be rescreened using 
their original screening number if there is a reasonable expectation that the reason(s) for the 
prior screen failure have resolved. 
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Page 82 of 88 
Section 8.2, Method of Numbering Subjects, 3rd Paragraph 
Previously read: 
A subject who has given informed consent (or for whom informed consent has been given) but 
does not fulfil, the criteria to participate in the study will receive a subject number and will be 
logged as a screening failure. If the screen failure becomes eligible at a later time, the original 
number assigned for that subject will be used. 
Now reads: 
A subject who has given informed consent (or for whom informed consent has been given) but 
does not fulfil, within 30 days before Visit 2, the criteria to participate in the study will receive 
a subject number and will be logged as a screening failure. If the screen failure becomes 
eligible at a later time, the original number assigned for that subject will be used. 
Section 8.6, Contraception and Pregnancy Avoidance Procedure, First Paragraph 
Previously read: 
Altropane contains 123I, a source of gamma radiation that is potentially harmful to a fetus. 
Therefore, care should be taken to avoid enrolling women of childbearing potential who may 
be or plan to become pregnant, and to ensure that women of childbearing potential who enroll 
in the study do not become pregnant during the study. Therefore, if the subject is a woman of 
childbearing potential, she must use a highly effective method of contraception from Screening 
until 30 days after the last administration of radiopharmaceutical, and the results of a serum or 
urine hCG pregnancy test, performed at Screening and on the day of radiopharmaceutical 
administration (with the result known before radiopharmaceutical administration), must be 
negative. 
Now reads: 
Altropane contains 123I, a source of gamma radiation that is potentially harmful to a fetus. 
Therefore, care should be taken to avoid enrolling women of childbearing potential who may 
be or plan to become pregnant, and to ensure that women of childbearing potential who enroll 
in the study do not become pregnant during the study. Therefore, if the subject is a woman of 
childbearing potential, she must use a highly effective method of contraception from Screening 
until 30 days after the administration of Altropane, and the results of a serum or urine hCG 
pregnancy test, performed at Screening and on the day of Altropane administration (with the 
result known before Altropane administration), must be negative. 
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GE HealthCare Confidential 
Page 83 of 88 
Section 9, Study Procedures, Table 2 
Previously read: 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
Obtain written informed consent1 
X 
Assess and record inclusion and exclusion criteria 
X 
Record demographic information 
X 
Record medical/surgical history 
X 
Obtain clinical diagnosis (ET for Part 1; dPS for Part 2) provided by referring physician 
X 
Obtain most recent prior DaTscan images 
X 
Record prior/concomitant medications 
X 
Measure and record vital signs (temperature, heart rate, respiration rate, BP)3 
X 
X 
X 
Perform and record limited physical examination4
X 
X 
X 
Record 12-lead ECG5 
X 
X 
X 
Obtain blood samples for clinical laboratory tests (serum biochemistry and hematology)6
X 
X 
X 
Obtain urine drug screen for drugs of abuse 
X 
X 
Perform serum or urine hCG pregnancy test (women of childbearing potential only)7 
X 
X 
Inspect IV catheter site8 
X 
X 
Administer approved thyroid blocking medication orally at least 1 hour ± 15 minutes 
before Altropane injection unless institutional protocols dictate otherwise 
X 
Insert IV catheter (22 gauge or larger) 
X 
Draw Altropane into sterile syringe, measure activity 
X 
Administer Altropane via IV catheter 
X 
Measure residual activity in syringe and delivery system (immediately after injection); 
record administered activity 
X 
Perform SPECT imaging2 
X 
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GE HealthCare Confidential 
Page 84 of 88 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
Monitor for adverse events/serious adverse events 
X 
X 
X 
BP = blood pressure; dPS = Degenerative Parkinsonian Syndrome; ECG = electrocardiogram; ET = essential tremor; hCG = human chorionic gonadotropin; IV = 
intravenous; SPECT = single photon emission computed tomography 
1Must be obtained before any other screening is done.  
2Imaging should start 15 to 20 minutes after injection and last 30 minutes.  
3Vital signs determined at screening, within 3 hours before injection, and within 60 minutes after imaging. 
4Limited physical examination (assessment of general appearance, lungs and heart) at screening, within 3 hours before injection and within 60 minutes after imaging. 
512-Lead ECG obtained at screening, within 3 hours before injection, and within 60 minutes after imaging.  
6Blood samples collected at screening, within 3 hours before injection, and within 60 minutes after imaging. 
7Women of childbearing potential must have a negative pregnancy test (serum or urine hCG) result at screening and within 3 hours before injection.  
8Inspect IV catheter site and record findings within 30 minutes before injection and within 60 minutes after imaging. 
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023


GE HealthCare Confidential 
Page 85 of 88 
Now reads: 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
Obtain written informed consent1 
X 
Assess and record inclusion and exclusion criteria 
X 
Record demographic information 
X 
Record medical/surgical history 
X 
Obtain clinical diagnosis provided by referring physician 
X 
Obtain most recent prior DaTscan images 
X 
Record prior/concomitant medications 
X 
Measure and record vital signs (temperature, heart rate, respiration rate, BP)3 
X 
X 
X 
Perform and record limited physical examination4
X 
X 
X 
Record 12-lead ECG5 
X 
X 
X 
Obtain blood samples for clinical laboratory tests (serum biochemistry and hematology)6
X 
X 
X 
Obtain urine drug screen for drugs of abuse 
X 
X 
Perform serum or urine hCG pregnancy test (women of childbearing potential only)7 
X 
X 
Inspect IV catheter site8 
X 
X 
Administer approved thyroid blocking medication orally at least 1 hour ± 15 minutes 
before Altropane injection unless institutional protocols dictate otherwise 
X 
Insert IV catheter (22 gauge or larger) 
X 
Draw Altropane into sterile syringe, measure activity 
X 
Administer Altropane via IV catheter 
X 
Measure residual activity in syringe and delivery system (immediately after injection); 
record administered activity 
X 
Perform SPECT imaging2 
X 
Monitor for adverse events/serious adverse events 
X 
X 
X 
BP = blood pressure; ECG = electrocardiogram; hCG = human chorionic gonadotropin; IV = intravenous; SPECT = single photon emission computed tomography 
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023


GE HealthCare Confidential 
Page 86 of 88 
Table 2 
Study Schedule of Events 
Activity/Action 
Visit 1: 
Screening 
Visit 2: Altropane SPECT 
(≤30 days after Visit 1) 
Visit 3: Follow-Up 
Phone Call 
(24 ± 6 hours after 
injection) 
Pre-Imaging Imaging2 Post-Imaging 
1Must be obtained before any other screening is done.  
2Imaging should start 15 to 20 minutes after injection and last 30 minutes.  
3Vital signs determined at screening, within 3 hours before injection, and within 60 minutes after imaging. 
4Limited physical examination (assessment of general appearance, lungs and heart) at screening, within 3 hours before injection and within 60 minutes after imaging. 
512-Lead ECG obtained at screening, within 3 hours before injection, and within 60 minutes after imaging.  
6Blood samples are collected at screening, within 3 hours before injection, and within 60 minutes after imaging. 
7Women of childbearing potential must have a negative pregnancy test (serum or urine hCG) result at screening and within 3 hours before injection.  
8Inspect IV catheter site and record findings within 30 minutes before injection and within 60 minutes after imaging. 
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GE HealthCare Confidential 
Page 87 of 88 
Section 9.1, Screening Visit (Visit 1), 5th Bullet 
Previously read: 
•
Baseline clinical diagnosis (ET in Part 1, or dPS in Part 2, if applicable) provided by the
referring physician, which must be consistent with the DaTscan images
Now reads: 
•
Baseline clinical diagnosis provided by the referring physician, which must be
consistent with the DaTscan images
Section 9.2, SPECT Imaging Visit (Visit 2), First Paragraph 
Previously read: 
The SPECT Imaging Visit (Visit 2) will take place within 30 days after the Screening visit. 
Now reads: 
The Altropane SPECT Imaging Visit (Visit 2) will take place within 30 days after the 
Screening visit. If DaTscan imaging was conducted recently, the Altropane SPECT imaging 
should occur at least 4 full days after the DaTscan imaging, to allow for elimination of 
DaTscan activity. 
Section 10.2.1, Clinical Laboratory Evaluation, 2nd Paragraph 
Previously read: 
Blood samples will be obtained for assessment of serum biochemistry and hematology 
parameters at the pre- and post-treatment time point ranges described in Table 2. It is 
anticipated that the maximum amount of blood taken will not be more than 20 mL for all the 
samples taken during the subject’s study participation. Samples will be analyzed at a central 
laboratory (for parameters, see Table 3). All blood samples will be processed and handled per 
standard laboratory procedures. All retained samples will be destroyed following institutional 
procedures after completion of the study. 
Now reads: 
Blood samples will be obtained for screening and for pre- and post-Altropane assessments of 
serum biochemistry and hematology parameters within the time point ranges described in 
Table 2. It is anticipated that the maximum amount of blood taken will not be more than 20 mL 
for all the samples taken during the subject’s study participation. Samples will be analyzed at a 
central clinical laboratory (for parameters, see Table 3).  
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023


GE HealthCare Confidential 
Page 88 of 88 
All blood samples will be processed and handled per standard laboratory procedures. All 
retained samples will be destroyed following institutional procedures after completion of the 
study. 
Section 12.9, Subgroup Analysis 
Previously read: 
Subgroup analyses by race, gender, and age category (e.g., <65 vs. >65) may be conducted as 
appropriate to the data. 
Now reads: 
Subgroup analyses by race, gender, and age category (e.g., <65 vs. ≥65) may be conducted as 
appropriate to the data. 
Section 13.7, Insurance 
Previously read: 
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. 
Now reads: 
This study is covered under the Sponsor’s Liability Insurance Policy. A Certificate of 
Insurance can be provided upon request. 
GE-278-001 Clinical Protocol Amendment A02
Version 1.0 Approved  12 Oct 2023


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Date / Name
Justification / Role
Signed By:
Date of signature: 12-Oct-2023 04:45:08 GMT+0000
Justification: Approved
Role:
Signed By: 
Date of signature: 12-Oct-2023 07:28:45 GMT+0000
Justification: Approved
Role: 
Signed By:
Date of signature: 12-Oct-2023 08:54:53 GMT+0000
Justification: Approved
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SAP_001.pdf: 
STATISTICAL ANALYSIS PLAN 
GE HealthCare 
GE-278-001 
GE HealthCare Confidential 
Version 1.0 
Page 1 of 27 
An open-label multicenter Phase 2 dose-evaluation study of Altropane (123I) 
Injection for striatal dopamine transporter visualization using SPECT brain 
imaging 
Clinical Study Protocol: GE-278-001 
Statistical Analysis Plan 
Version 1.0 
05 September 2023 
GE-278-001 Statistical Analysis Plan
Version 1.0 Approved  06 Sep 2023
ClinicalTrials.gov ID: NCT05636852


STATISTICAL ANALYSIS PLAN 
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Version History 
Version 
Version Date 
Author/Title/Organization 
Summary of Key Changes 
1.0 
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Fortrea 
Initial Release 
 
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Document Approval 
 
Author 
Written By 
 
Signature 
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Date 
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Role 
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Approval 
Approved By 
 
Signature 
      SEE ELECTRONIC SIGNATURE 
Date 
      SEE ELECTRONIC SIGNATURE 
Role 
 GE HealthCare 
 
 
Approval 
Approved By 
 
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Date 
      SEE ELECTRONIC SIGNATURE 
Role 
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STATISTICAL ANALYSIS PLAN 
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TABLE OF CONTENTS 
1 
INTRODUCTION ................................................................................................ 8 
2 
STUDY DESIGN ................................................................................................. 8 
2.1 
Overview .................................................................................................. 8 
2.2 
Sample Size and Number of Planned Centers .......................................... 9 
2.3 
Enrollment .............................................................................................. 10 
2.4 
Screen Failure ......................................................................................... 10 
2.5 
Randomization and Blinding .................................................................. 10 
2.6 
Study Completion ................................................................................... 10 
2.7 
Study Exit ............................................................................................... 10 
3 
STUDY DATA COLLECTION SCHEDULE ................................................... 11 
3.1 
Screening Visit (Visit 1) ......................................................................... 11 
3.2 
SPECT Imaging Visit (Visit 2) ............................................................... 12 
3.2.1 
Within 3 hours before the IMP injection .............................. 12 
3.2.2 
One hour ± 15 minutes before injection ............................... 12 
3.2.3 
Within 30 minutes before injection ...................................... 12 
3.2.4 
Altropane administration ...................................................... 12 
3.2.5 
SPECT imaging .................................................................... 12 
3.2.6 
Within 60 minutes after imaging .......................................... 12 
3.3 
24-hour Follow-Up Visit (Visit 3) .......................................................... 13 
3.4 
Unscheduled Visits ................................................................................. 13 
4 
COLLECTED DATA ELEMENTS ................................................................... 13 
4.1 
Clinical Laboratory Parameters .............................................................. 13 
4.2 
Vital Signs .............................................................................................. 14 
4.3 
Electrocardiograms ................................................................................. 15 
4.4 
Limited Physical Examination................................................................ 15 
4.5 
AEs and SAEs ........................................................................................ 15 
4.6 
Demographic Data .................................................................................. 16 
4.7 
Medical and Surgical History ................................................................. 16 
4.8 
Prior/Concomitant Medication ............................................................... 16 
4.9 
Blinded Image Evaluation ...................................................................... 16 
5 
OBJECTIVES ..................................................................................................... 16 
5.1 
Primary Objective ................................................................................... 16 
5.2 
Secondary Objective ............................................................................... 16 
6 
PART 1 ENDPOINTS ........................................................................................ 17 
6.1 
Primary Endpoint .................................................................................... 17 
6.2 
Secondary Endpoints .............................................................................. 17 
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6.2.1 
Secondary Efficacy Endpoints .............................................. 17 
6.2.2 
Secondary Safety Endpoints ................................................. 17 
6.3 
 ............................................................................ 17 
6.3.1 
 ........................................... 17 
7 
PART 2 ENDPOINTS ........................................................................................ 18 
7.1.1 
Primary Efficacy Endpoint ................................................... 18 
7.1.2 
Secondary Efficacy Endpoints .............................................. 18 
7.1.3 
Secondary Safety Endpoints ................................................. 18 
7.1.4 
 ........................................... 18 
8 
ANALYSIS CONVENTIONS ........................................................................... 18 
8.1 
General Considerations ........................................................................... 18 
8.2 
Data Presentation .................................................................................... 19 
8.3 
Analysis Sets........................................................................................... 20 
8.4 
Statistical Hypothesis and Level of Significance ................................... 21 
8.5 
Handling of Missing Data ....................................................................... 21 
8.6 
Handling of Uninterpretable Images ...................................................... 21 
8.7 
Rules for Excluding Subjects from Analysis .......................................... 21 
8.8 
Interim Analysis ..................................................................................... 21 
8.9 
Subgroup Analysis .................................................................................. 21 
8.10 
Statistical Software ................................................................................. 22 
9 
STATISTICAL ANALYSES ............................................................................. 22 
9.1 
Primary Efficacy Analysis ...................................................................... 22 
9.2 
Secondary Efficacy Analyses ................................................................. 22 
9.2.1 
Reader Assessment of Image Quality ................................... 22 
9.2.2 
Reader Confidence in Striatal Visualization ........................ 22 
9.2.3 
Inter-Reader Agreement ....................................................... 23 
9.2.4 
Intra-Reader Reproducibility (Part 2 Only) .......................... 23 
9.3 
Exploratory Efficacy Analysis................................................................ 23 
9.3.1 
Supportive Analyses ............................................................. 23 
9.4 
Secondary Safety Analysis ..................................................................... 23 
9.4.1 
Analysis of Adverse Events .................................................. 23 
9.4.2 
Analysis of Clinical Laboratory Data ................................... 24 
9.4.3 
Analysis of Vital Signs ......................................................... 24 
9.4.4 
Analysis of Electrocardiograms Data ................................... 25 
9.4.5 
Analysis of Limited Physical Examination Data .................. 25 
9.5 
Subject Disposition and Population Assignment.................................... 25 
9.6 
Demographic and Baseline Characteristics ............................................ 26 
9.7 
Protocol Deviations ................................................................................ 26 
9.8 
Medical and Surgical History ................................................................. 26 
9.9 
Prior/Concomitant Medications .............................................................. 26 
9.10 
Study Drug Exposure and Compliance .................................................. 26 
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10 
DEVIATION FROM PLANNED ANALYSES ................................................ 26 
11 
CHANGES FROM THE PROTOCOL-SPECIFIED ANALYSIS .................... 26 
12 
REFERENCES ................................................................................................... 26 
 
 
 
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List of Abbreviations and Definitions of Terms 
Abbreviation/Term 
Definition 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
BIE 
Blinded Image Evaluation 
BP 
Blood Pressure 
CRF 
Case Report Form 
DAT 
Dopamine Transporter 
dPS 
degenerative Parkinsonian Syndrome(s) 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
ET 
Essential Tremor 
hCG 
Human Chorionic Gonadotropin 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation (formerly International 
Conference on Harmonisation) 
IMP 
Investigational medicinal product 
IV 
Intravenous 
PD 
Parkinson’s Disease 
PS 
Parkinsonian Syndrome(s) 
SADR 
Suspected Adverse Drug Reaction 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBR 
Striatal Binding Ratio 
SPECT 
Single Photon Emission Computed Tomography 
TEAE 
Treatment-Emergent AE 
 
 
 
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1 
INTRODUCTION 
This statistical analysis plan (SAP) describes the planned statistical methods to be used during the 
reporting and analysis of data collected under the Clinical Study Protocol, “An open-label 
multicenter Phase 2 dose-evaluation study of Altropane (123I) Injection for striatal dopamine 
transporter visualization using SPECT brain imaging”. This SAP should be read in conjunction 
with the study protocol and associated case report forms (CRFs). This version of the analysis plan 
has been developed with respect to the current approved study protocol v2.0. Any revisions to the 
protocol or CRFs that impact the planned analyses may require updates to the SAP. If there are 
any discrepancies between the SAP and the protocol, the SAP will prevail. The SAP will be 
finalized and approved (i.e., signed by all relevant parties) before the study database is locked. 
This SAP is written with consideration of the recommendations outlined in the International 
Council for Harmonisation (ICH) E3 guideline Structure and Content of Clinical Study Reports, 
ICH E8 guideline General Considerations for Clinical Trials, and ICH E9 guideline Statistical 
Principles for Clinical Trials.1,2,3 
2 
STUDY DESIGN 
2.1 
Overview 
Movement disorders are common in elderly adults, yet arriving at a specific diagnosis can be 
difficult even for movement disorder experts. A subgroup of movement disorders includes the 
Parkinsonian syndromes (PS; also called Parkinsonism), of which the most common type is 
Parkinson’s disease (PD). Some types of PS, such as PD, are neurodegenerative, i.e., they involve 
nigrostriatal neurodegeneration, an irreversible loss of dopaminergic nigrostriatal neurons. In 
neurodegenerative PS, the reduction in nigrostriatal neurons is accompanied by a reduction in the 
presynaptic membrane expression of the dopamine transporter (DAT) protein. Hence, the ability 
to visualize striatal DAT (or its loss) during life using diagnostic imaging is a valuable adjunct to 
clinical examination of patients with suspected Parkinsonian symptoms. The development of 
radiolabeled tropane derivatives with high binding affinity for the DAT, which act as functional 
tracers for DAT, make it possible to use single photon emission computed tomography (SPECT) 
imaging to visualize the distribution and density of nigrostriatal DAT in the living brain. 
One such tracer is Altropane (123I) Injection (hereafter referred to as Altropane). It is being 
developed by GE HealthCare as a striatal SPECT imaging agent as an alternative to DaTscan (an 
approved DAT imaging agent). An important potential advantage of Altropane over DaTscan is 
the rapid uptake of the molecule resulting in significantly decreased time from injection to 
imaging (15 minutes with Altropane vs. 3 to 6 hours with DaTscan). In addition, Altropane 
requires only 30 minutes of time in the scanner compared to the need to acquire 1.5 million 
counts DaTscan (approximately 45 minutes). 
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To date, 10 clinical investigations of Altropane have been completed. These include 3 Phase 1 
studies, 4 Phase 2 studies, and 3 Phase 3 studies. These prior studies indicated that an 8-mCi dose 
of Altropane would be appropriate for clinical use. However, the question arose whether a 5-mCi 
dose (closer to the approved dose range of 3 to 5 mCi for DaTscan) would also be acceptable. 
This study is a prospective, multicenter, open-label, Phase 2 dose-evaluation study to determine if 
a 5-mCi Altropane dose would be acceptable for subsequent clinical studies including a Phase 3 
study. This study has 2 parts: Part 1, which will definitely be conducted, and Part 2, which will 
only be conducted if Part 1 shows the 5-mCi dose to be acceptable.  
In Part 1, subjects with known normal striatal uptake on DaTscan images obtained within 1 year 
(preferably within 6 months) before study enrollment and who have a clinical diagnosis of 
essential tremor (ET) will undergo striatal SPECT imaging following intravenous (IV) 
administration of 5 mCi of Altropane. In a blinded image evaluation (BIE), 5 trained expert 
blinded readers will interpret, in random order, the Altropane 5-mCi images collected in this 
study along with normal and abnormal 8-mCi Altropane images collected in prior studies; the 8-
mCi images will be included to reduce the potential for bias if the blinded readers read only 
normal images. Endpoints that will be evaluated visually in the BIE are striatal visualization, 
reader confidence in striatal visualization, and image quality. Inter-reader agreement will be 
determined. 
 
 
If the 5-mCi dose of Altropane is found to be acceptable in Part 1, then Part 2 will be initiated; 
otherwise, the study will end after Part 1 and the 8-mCi dose will be selected for subsequent 
clinical studies. If Part 2 is conducted, then an additional endpoint will be intra-reader 
reproducibility. 
2.2 
Sample Size and Number of Planned Centers 
Based on prior experience with DaTscan, it is expected that the probability of a correct subject 
classification based on Altropane images will be 92% in Part 1 and 91% in Part 2 (if it is 
conducted). 
In Part 1, at least 10 subjects with normal striatal uptake will be sufficient to determine whether 
or not the 5-mCi Altropane dose provides acceptable visualization of normal striatal uptake. Ten 
subjects with normal striatal uptake can achieve 62% power to detect whether the 5-mCi dose can 
result in a rate of correct subject classification of 70% or higher by a 1-sided exact test at a target 
significance level of 0.04. These results assume that the true rate of correct subject classification 
under the null hypothesis is 92% in Part 1.  
If Part 2 proceeds, then at least 20 subjects with abnormal striatal uptake will be sufficient to 
determine whether or not to proceed with the 5-mCi dose in Phase 3. Twenty subjects with 
abnormal striatal uptake will have 76% power to detect whether the 5-mCi dose can result in a 
rate of correct subject classification of 75% or higher under the assumption that the true rate of 
correct subject classification is 91%. 
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Subjects will be enrolled at up to 5 centers in the United States.  
2.3 
Enrollment 
In Part 1, subjects with normal striatal uptake (ET subjects) on prior DaTscan images will be 
recruited at each study center. Potentially eligible subjects will be asked by study personnel about 
their willingness to participate in this study. Sites may identify subjects with abnormal striatal 
uptake (dPS subjects) for Part 2 but may not enroll them unless the decision is made by GE 
HealthCare to proceed with Part 2. 
2.4 
Screen Failure 
Screen failures are subjects who consent to participate in the clinical study but do not meet all 
inclusion criteria or meet at least one of the exclusion criteria. The subjects with screen failures 
will receive a subject number. Demographic and other data will be collected for all screen 
failures. Screen failures may be rescreened using their original screening number if there is a 
reasonable expectation that the reason(s) for the prior screen failure have resolved. 
2.5 
Randomization and Blinding 
No blinding of the investigational medicinal product (IMP) will be performed. In the BIE, images 
will be presented in randomized order and readers will be blinded to clinical information, the 
identity of the tracer and tracer doses used to image subjects, and to the study protocol.  
2.6 
Study Completion 
Subjects will have completed their involvement with the study when their 24-hour follow-up visit 
has been completed. 
2.7 
Study Exit 
Should a subject decide to withdraw after administration of the IMP (i.e., Altropane), 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 
evaluation at the time of the subject’s withdrawal should be made and an explanation given of 
why the subject is withdrawing or is being withdrawn from the study. The reason for withdrawal 
must be noted in the electronic case report form (eCRF). If the reason for withdrawal is an 
adverse event (AE), monitoring will continue until the outcome is evident. The specific event or 
test result(s) must be recorded in the eCRF. 
Furthermore, a subject will be considered lost to follow-up if he or she repeatedly fails to 
participate in scheduled follow-up and cannot be contacted by the study site. Should the subject 
continue to be unreachable, he/she will be considered to have withdrawn from the study.  
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3 
STUDY DATA COLLECTION SCHEDULE 
The study will require 3 visits for each subject: a screening visit (Visit 1) within 30 days before 
the SPECT imaging visit (Visit 2), followed by a safety follow-up phone call (Visit 3) 24 hours 
after Visit 2. 
3.1 
Screening Visit (Visit 1) 
A Screening visit will take place up to 30 days before the SPECT imaging visit (Visit 2). Signed 
and dated informed consent must be obtained from all subjects prior to their entering the study 
and any screening procedures being performed. All subjects must satisfy all the inclusion criteria 
and none of the exclusion criteria.  
At the Screening visit, the following data will be obtained and recorded on the relevant pages of 
the eCRF. Data that are collected through any source of data including Electronic Data Capture 
(EDC) device are specified below. 
▪ Inclusion and exclusion criteria 
▪ Demographic data 
▪ Medical/Surgical history 
▪ Most recent prior DaTscan images (obtained within 1 year (preferably 6 months) before 
screening) showing normal striatal uptake (Part 1) or abnormal striatal uptake (Part 2, if 
applicable). The conclusions of the assessment will be collected through EDC.  
▪ Baseline clinical diagnosis (ET in Part 1, or dPS in Part 2, if applicable) provided by the 
referring physician, which must be consistent with the DaTscan images 
▪ Prior/concomitant medications 
▪ Vital signs (temperature, heart rate, respiration rate, blood pressure [BP]) 
▪ Limited physical examination (general appearance, lungs, and heart) 
▪ 12-lead electrocardiogram (ECG) 
▪ Urine sample (for testing for drugs of abuse) 
▪ Blood for laboratory parameters (hematology and serum biochemistry) 
▪ Serum or urine human chorionic gonadotropin (hCG) pregnancy test for women of child-
bearing potential 
▪ AEs/Serious AEs (SAEs) 
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3.2 
SPECT Imaging Visit (Visit 2) 
The SPECT Imaging Visit will take place within 30 days after the Screening visit. The following 
data will be collected within the specified time windows: 
3.2.1 
Within 3 hours before the IMP injection 
▪ Limited physical examination (general appearance, lungs and heart) 
▪ Update prior/concomitant medications 
▪ Urine drug screen (for testing for drugs of abuse) 
▪ Vital signs (temperature, heart rate, respiration rate, BP) 
▪ 12-lead ECG 
▪ Serum or urine hCG pregnancy test for women of child-bearing potential 
▪ Blood sampling for serum biochemistry, hematology, and pregnancy (if opting for serum 
test) 
3.2.2 
One hour ± 15 minutes before injection 
▪ Administration of an approved thyroid blocking medication 
3.2.3 
Within 30 minutes before injection 
▪ Findings from the IV catheter site inspection (e.g., bleeding, hematoma, infection) 
3.2.4 
Altropane administration 
▪ Actual IMP administered activity 
3.2.5 
SPECT imaging 
▪ SPECT imaging to start 15 to 20 minutes after Altropane injection and last for 30 minutes 
3.2.6 
Within 60 minutes after imaging 
▪ Findings from the IV catheter site inspection 
▪ Update prior/concomitant medications 
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▪ Vital signs (temperature, heart rate, respiration rate, BP) 
▪ Limited physical examination (general appearance, lungs and heart) 
▪ 12-lead ECG 
▪ Blood sampling for serum biochemistry and hematology 
3.3 
24-hour Follow-Up Visit (Visit 3) 
Subjects will be contacted by telephone 24±6 hours after Visit 2 dosing to: 
▪ Update concomitant medications 
▪ Assess for any AEs/SAEs 
3.4 
Unscheduled Visits 
▪ Date and reason for the visit 
▪ Additional procedures will be captured through the eCRF 
4 
COLLECTED DATA ELEMENTS 
4.1 
Clinical Laboratory Parameters 
Table 1 presents the clinical laboratory parameters. Blood samples will be obtained for 
assessment of serum biochemistry and hematology parameters at the pre- and post-treatment time 
points as specified in Section 3 of this document, and urine screenings will be performed for 
drugs of abuse. In addition, serum, or urine hCG pregnancy test will be performed for women of 
childbearing potential. Any abnormal laboratory findings that constitute an AE 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. 
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Table 1 
Clinical Laboratory Parameters 
Serum Biochemistry 
Hematology 
Urine Screenings 
• 
Alanine aminotransferase 
(ALAT) 
• 
Albumin 
• 
Alkaline phosphatase 
• 
Amylase 
• 
Aspartate aminotransferase 
(ASAT) 
• 
Bicarbonate 
• 
Bilirubin (total, direct, 
indirect) 
• 
Calcium 
• 
Chloride 
• 
Creatine phosphokinase 
(CPK), total 
• 
Creatinine 
• 
Gamma-glutamyltransferase 
(G-GT) 
• 
Glucose 
• 
Lactate dehydrogenase 
• 
Phosphorous 
• 
Potassium 
• 
Protein (total) 
• 
Sodium 
• 
Urea nitrogen 
• 
Uric acid 
• 
Red blood cell 
(RBC) count 
• 
Platelet count 
• 
White blood cell 
(WBC) count 
Drugs of Abuse 
• 
Amphetamine  
• 
Barbiturate  
• 
Benzodiazepine 
• 
Buprenorphine 
• 
Cocaine 
• 
Fentanyl 
• 
Tetrahydrocannabinol (THC) 
• 
3,4-methylenedioxymethamphetamine 
(MDMA; “Molly”) 
• 
Methadone 
• 
Methamphetamine  
• 
Opiates  
• 
Oxycodone 
• 
Tricyclic Antidepressants 
 
Pregnancy 
• 
Human chorionic gonadotropin (hCG; unless 
serum tested) 
 
4.2 
Vital Signs 
Vital signs consist of temperature, heart rate, respiration rate, and blood pressure collected at time 
points as specified in Section 3 of this document. Table 2 presents the vital sign parameters and 
the normal limits. 
Table 2 
Criteria for Normal Limits for Vital Signs 
Vital Sign Parameter 
Normal Limits 
Low 
High 
Systolic BP (mmHg) 
85 
139 
Diastolic BP (mmHg) 
60 
89 
Heart Rate (bpm) 
60 
100 
Respiration Rate (rpm) 
12 
22 
Body Temperature 
36.4C (97.5F) 
37.7C (99.5F) 
 
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4.3 
Electrocardiograms 
A standard 12-lead ECG will be obtained at screening and at the pre- and post-imaging time 
points as specified in Section 3. ECGs will be interpreted by the investigator or by a designee 
who is qualified by the institution to read ECGs and report the data at the investigative site. The 
ECG variables and normal limits are presented in Table 3.  
Table 3 
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 
(Gender not specified) 
- 
≤440 
QTc intervala 
(Gender not specified) 
- 
≤440 
a No lower boundary set for QTc. 
 
4.4 
Limited Physical Examination 
The physical examination will include recording an assessment for the presence of abnormalities 
of the following: general appearance, lungs and heart, and inspection of the IV catheter site 
before and after imaging. Abnormal injection site findings may include, but are not limited to 
extravasation, bleeding, hematoma, redness, and infection. Abnormal injection site findings are to 
be recorded as AEs in the eCRF. A new abnormal physical finding is one that occurs when a 
subject’s normal baseline physical examination becomes abnormal post-baseline. A worsening 
abnormal physical finding is one that was present at baseline (pre-dosing) that later becomes 
worse. New abnormal physical findings and worsening abnormal physical findings should be 
reported as AEs.  
4.5 
AEs and SAEs 
In addition to AEs and SAEs, treatment-emergent AEs (TEAEs), adverse drug reactions (ADRs), 
suspected adverse drug reactions (SADRs), and suspected unexpected serious adverse drug 
reactions will be collected. Furthermore, the investigator will make an assessment of the highest 
intensity for each AE and SAE reported during the study and assign it to one of the following 
categories: Mild, Moderate, and Severe. The causality of the AE/SAE will be also reported as 
Related or Unrelated to the IMP. 
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4.6 
Demographic Data  
Subject demographic data to be recorded at Screening includes: age, race, ethnicity, gender, 
weight, and height. Body mass index will be calculated from height and weight. 
4.7 
Medical and Surgical History 
Each subject’s relevant medical and surgical history will be recorded at Screening. 
4.8 
Prior/Concomitant Medication 
Each subject’s prior/concomitant medications will be recorded at Screening, Visit 2, and the 
24-hour follow-up call (post-Visit 2). The thyroid blocking agent administered prior to Altropane 
SPECT should be recorded separately on the appropriate eCRF page. All therapies and 
medications will be encoded according to a current well-organized dictionary of medical codes. 
4.9 
Blinded Image Evaluation 
Visual interpretation of the Altropane SPECT images will be conducted by 5 independent expert 
readers who are blinded to each subject’s clinical information, and who are not otherwise 
involved in the study. The readers will assess: 
▪ Image interpretation (normal or abnormal) 
▪ Confidence in striatal visualization (high medium, or low) 
▪ Image quality (excellent, good, fair, poor, or unevaluable) 
 
5 
OBJECTIVES 
5.1 
Primary Objective 
▪ To determine whether a 5-mCi dose of Altropane is acceptable for visualizing the right 
and left striata. 
5.2 
Secondary Objective 
▪ To evaluate the safety of Altropane (using the endpoints AE and SAE frequency, and 
changes from baseline in vital signs, physical examination, ECG, and laboratory 
parameters). 
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6 
PART 1 ENDPOINTS  
6.1 
Primary Endpoint 
▪ Striatal visualization, reported as a forced choice of either normal (caudate and putamen 
fully visible on left and right, or with small insignificant defects) or abnormal (unilateral 
or bilateral reduced) striatal uptake.  
6.2 
Secondary Endpoints 
6.2.1 
Secondary Efficacy Endpoints 
▪ Reader confidence in striatal visualization 
▪ Reader assessment of image quality 
▪ Inter-reader agreement 
6.2.2 
Secondary Safety Endpoints 
▪ Subjects reporting 1 or more AE 
▪ ADR frequency 
▪ Changes from baseline in vital signs, physical examination, ECG, or laboratory 
parameters 
6.3 
 
6.3.1 
 
 
 
 
 
 
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7 
PART 2 ENDPOINTS  
7.1.1 
Primary Efficacy Endpoint 
▪ Striatal visualization, reported as a forced choice of either normal (caudate and putamen 
fully visible on left and right, or with small insignificant defects) or abnormal (unilateral 
or bilateral reduced) striatal uptake. 
7.1.2 
Secondary Efficacy Endpoints 
▪ Reader confidence in striatal visualization 
▪ Reader assessment of image quality 
▪ Inter-reader agreement 
▪ Intra-reader reproducibility (including the images from Part 1) 
7.1.3 
Secondary Safety Endpoints 
▪ Subjects reporting 1 or more AE 
▪ ADR frequency 
▪ Changes from baseline in vital signs, physical examination, ECG, or laboratory 
parameters 
7.1.4 
 
 
 
 
 
 
8 
ANALYSIS CONVENTIONS 
8.1 
General Considerations 
Tables and listings will be prepared in accordance with the current the International Council for 
Harmonisation (ICH) Guidelines.  The information and explanatory notes to be provided in the 
“footer” or bottom of each table and listing will include the following information: 
1. Date and time of output generation 
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2. SAS® program name, including the path that generates the output 
3. Any other output specific details that require further elaboration 
4. Source data listing number to identify the data listing(s) that are the source for the table 
In general, tables will present results for all subjects within the determined analysis set. Column 
entries will display findings associated to the topic for all subjects of the analysis set.  Row 
entries in tables are made only if data exists for at least one subject (i.e., a row with all zeros will 
not appear). Summary tables will clearly indicate the number of subjects to which the data apply 
and unknown or not performed will be distinguished from missing data.  
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 eCRF 
and entered into the database will be provided in separate data listings showing individual subject 
values. Summary tables and data listings will be presented overall, separated by clinical diagnosis 
at baseline and by study part (Part 1 and Part 2 [if applicable]).  
8.2 
Data Presentation 
The following conventions will be applied to all data presentations and analyses. 
▪ Summary statistics for categorical variables will consist of the number and percentage of 
responses in each level.  The number and percentage of responses will be presented in the 
form XX (XX.X%). 
▪ Unless specified differently, summary statistics for discrete variables will consist of the 
counts and percentages.  
▪ Unless specified differently, summary statistics for continuous variables will consist of 
the number of subjects in the analysis (n), mean, median, standard deviation (SD), 
minimum, and maximum values.  
▪ Unless specified differently, all mean and median values will be formatted to one more 
decimal place than the measured value.  Standard deviation values will be formatted to 2 
more decimal places than the measured value.  Minimum and maximum values will be 
presented with the same number of decimal places as the measured value. 
▪ All p-values, if applicable, will be rounded to 4 decimal places.  All p-values that round to 
0.0000 will be presented as ‘<0.0001’ and p-values that round to 1.0000 will be presented 
as ‘>0.9999’.  Two-sided P-values <0.05 will be considered to be statistically significant 
unless otherwise specified. 
▪ Study Day 1 is defined as the date at which the patient receives IMP.  All study days are 
determined relative to Day 1.   
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▪ Study days prior to Day 1 will be calculated as: 
Study Day = Assessment Date – Injection Date 
▪ Study days after Day 1 will be calculated as: 
Study Day = Assessment Date – Injection Date + 1. 
▪ The last non-missing observation prior to administration of IMP will be used as the 
baseline value for calculating changes from baseline after administration of IMP. 
▪ Change from baseline will be calculated as follows:  
Change = post-baseline value - baseline value 
The baseline value is defined as the most recent non-missing measurement prior to or on the 
IMP injection.  
▪ Date variables will be formatted as DDMMMYYYY for presentation. Unless complete 
dates are needed for calculation of durations or days between events, incomplete dates 
will not be imputed, but the available information will be listed (for example, 
__MAY2022 or _____2022). 
o If complete dates are needed for calculation of durations or days between events, 
but complete date was not reported/recorded, a clinically meaningful and/or 
conservative imputation will be applied to missing date parts. 
o Any imputation of incomplete dates will be included as a footnote to applicable 
tables, listings, or figures.  
▪ Time variables will be displayed as 24-hour clock time HH:MM. 
▪ Tables, figures, and listings will be presented in landscape orientation. 
8.3 
Analysis Sets 
The analysis sets are defined as follows: 
▪ Safety Analysis Set: The Safety Analysis Set is defined as all subjects who receive any 
amount of Altropane. 
▪ Full Analysis Set: The Full Analysis Set is defined as all subjects who receive any amount 
of Altropane and have an Altropane image interpretation. 
For Part 1 the dose-evaluation (efficacy) analysis will be based on the Full Analysis Set. For Part 
2 (if conducted) the dose-evaluation (efficacy) will also be based on the Full Analysis Set. 
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8.4 
Statistical Hypothesis and Level of Significance 
There are no formal tests of statistical hypotheses conducted in this study. The 5-mCi dose will 
be considered to show acceptable striatal visualization if the percentage of correct majority 
classifications is greater than 70% in Part 1 and 75% in Part 2 (if applicable).  
8.5 
Handling of Missing Data 
The efficacy (dose-evaluation) analysis is based on the Full Analysis Set; all subjects in that 
analysis set will have an image. Other missing values will not be imputed, and only observed 
values will be used in data analyses and reports, unless otherwise specified.  
8.6 
Handling of Uninterpretable Images 
During the BIE the determination of striatal visibility will be forced so all images are considered 
“interpretable” with respect to the primary objective. Therefore, no images will be categorized as 
“uninterpretable”.  
8.7 
Rules for Excluding Subjects from Analysis 
All dosed subjects will be included in the analysis sets according to the analysis sets defined in 
Section 8.3 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 a 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. 
8.8 
Interim Analysis 
Results from Part 1 will be analyzed and based on the results a decision will be made whether or 
not to proceed to Part 2. 
8.9 
Subgroup Analysis  
Subgroup analyses by race, gender, and age category (e.g., <65 vs. >65) may be conducted as 
appropriate to the data.  
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8.10 
Statistical Software 
All statistical analysis, tables, listings, and figures described in this SAP will be produced using 
SAS® software (Version 9.4 or higher) in SAS Grid Manager Environment. 
9 
STATISTICAL ANALYSES 
9.1 
Primary Efficacy Analysis 
The following primary efficacy analysis will be performed for Full Analysis Set.  
▪ Number and percentage of correct classifications of 5-mCi Altropane images from 
subjects with normal striatal uptake (Part 1) 
▪ Number and percentage of correct classifications of 5-mCi Altropane images from 
subjects with abnormal striatal uptake (Part 2, if applicable) 
The correctness of image classification will be determined from the majority interpretation of the 
5 expert blinded readers (at least 3 of 5 readers). The 5-mCi dose will be considered to show 
acceptable striatal visualization if the percentage of correct majority classifications is greater than 
70% in Part 1 and 75% in Part 2 (if applicable).  
9.2 
Secondary Efficacy Analyses 
The following secondary efficacy analyses will be performed for Full Analysis Set.  
9.2.1 
Reader Assessment of Image Quality 
▪ Number and percentage of Part 1 subjects with 5-mCi Altropane image quality judged as 
excellent or good 
▪ Number and percentage of subjects in Part 2 (if applicable) with 5-mCi Altropane image 
quality judged as excellent or good  
The quality will be graded as excellent, good, fair, poor, or unevaluable. The results of this 
secondary analysis will be considered consistent with the results of the primary analysis if the 
percentage of images with excellent or good majority ratings is greater than 70%.  
9.2.2 
Reader Confidence in Striatal Visualization 
▪ Number and percentage of Part 1 subjects with high confidence rating for their 5-mCi 
Altropane images 
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▪ Number and percentage of Part 2 subjects (if applicable) with high confidence rating for 
their 5-mCi Altropane images 
The confidence level will be graded as high, medium, or low. The results of this secondary 
analysis will be considered consistent with the results of the primary analysis if the percentage of 
images with high majority ratings of confidence is at least 70%.  
9.2.3 
Inter-Reader Agreement 
▪ Number and percentage of images for which 5, 4, and 3 readers, respectively, are in 
agreement on the subject classification for Part 1, and, if applicable, Part 2. 
9.2.4 
Intra-Reader Reproducibility (Part 2 Only) 
▪ Number and percentage of subjects for whom each reader's second image interpretation 
agrees with his/her first image interpretation. 
If Part 2 is conducted, each reader will read all images (including the images from Part 1) at least 
twice to determine intra-reader reproducibility. 
9.3 
 
  
 
 
9.3.1 
 
 
 
 
9.4 
Secondary Safety Analysis 
Safety analyses will be performed for treatment-emergent AEs, treatment-emergent SAEs, 
ADRs, serious ADRs, vital signs, physical examination, ECG, and laboratory tests. The 
secondary safety analysis will be performed using the Safety Analysis Set.  
9.4.1 
Analysis of Adverse Events 
AEs and SAEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
and all reported events will be listed for the Safety Analysis Set.  The number and percentage of 
subjects with 1 or more treatment-emergent AEs will be summarized by System Organ Class 
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(SOC) and Preferred Term (PT) by Part 1 (and, if applicable, Part 2), and overall. A TEAE will 
be defined as an AE that begins or worsens between the start of IMP administration and the end 
of the follow-up period. Summaries will also be presented by AE intensity (severity) and 
relationship to IMP (Related or Not related [Unrelated]) as assessed by the investigator. 
Treatment-emergent SAEs will also be presented by Part 1 (and, if applicable, Part 2, and 
overall). All AEs will be listed. In addition to the data recorded in the database, the listings will 
include derived onset time and duration. Onset time will be calculated from the time of the start 
of the injection for TEAEs only. Narratives for deaths, SAEs, AEs leading to discontinuation and 
other clinically meaningful TEAEs will be included in the CSR. Similar analyses will be performed 
for ADRs.  
9.4.2 
Analysis of Clinical Laboratory Data 
Descriptive statistics will be displayed for the observed values and changes from baseline in lab 
parameters. In addition, for each clinical laboratory variable and each time point, the following 
safety endpoints will be summarized by counts and percentages overall and by part 1 or part 2: 
▪ 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. 
9.4.3 
Analysis of Vital Signs 
Descriptive statistics will be displayed for the observed values and changes from baseline in vital 
signs. For each vital-sign variable and each time point, the following safety endpoints will be 
summarized by counts and percentages overall and by dose group: 
▪ 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 BP, 10 mm Hg for 
diastolic BP, 10 beats per minute for heart rate, 1.5oC for body temperature, or 10 breaths 
per minute for respiration rate). 
▪ The occurrence of post-administration values outside the normal limits. Shift tables based 
on the normal range will be prepared.  
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9.4.4 
Analysis of Electrocardiograms Data 
Descriptive statistics will be displayed for the observed values and changes from baseline in ECG 
data. For each ECG variable and each time-point, the following safety endpoints will be 
summarized by counts and percentages overall and by dose group: 
▪ 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: 
<30ms, 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. Shift tables based on the normal range will be prepared.  
ECGs for which the overall interpretation was abnormal will be summarized overall and by dose 
group by counts and percentages at each post-administration time point. 
QTc correction: 
Two correction formulae will be employed in analyzing QTc data in an attempt to reduce the bias 
resulting from over- or under-correction: 
 
Bazett’s: 𝑄𝑇𝑐𝐵=
𝑄𝑇
√𝑅𝑅 
 
Fridericia’s: 𝑄𝑇𝑐𝐹=
𝑄𝑇
√𝑅𝑅
3
 
9.4.5 
Analysis of Limited Physical Examination Data 
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 
overall and by Part 1 or Part 2. Shift tables will be prepared.  
9.5 
Subject Disposition and Population Assignment 
Subject disposition and population assignment will be listed. A summary table will be provided 
based on the Safety Analysis Set. Screen failure data summary table including the reason for 
screen failure will be provided separately, based on the screened subjects population. 
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9.6 
Demographic and Baseline Characteristics 
Demographic information (age, height, weight, and body mass index) will be summarized using 
descriptive statistics. Gender and race will be summarized by counts and percentages. The 
demographics and baseline characteristics will be presented for the Safety Analysis Set.  
9.7 
Protocol Deviations 
The protocol deviations will be listed for all screened subjects in accordance with ICH E3-GCP. 
All protocol deviations will be considered prior to database lock.  
9.8 
Medical and Surgical History 
Medical and surgical histories will be summarized by counts and percentages.  
9.9 
Prior/Concomitant Medications 
Prior and concomitant medications will be recorded and coded using a standard classification 
system and grouped by primary and secondary classes, if applicable. 
9.10 
Study Drug Exposure and Compliance 
Administered doses of Altropane will be summarized by volume (in mL) and radioactivity 
administered (in MBq) in Part 1 and, if applicable, in Part 2. The amount and type of medication 
used for thyroid blockade for each subject will also be summarized. 
10 
DEVIATION FROM PLANNED ANALYSES 
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. 
11 
CHANGES FROM THE PROTOCOL-SPECIFIED ANALYSIS 
There were no significant changes from the protocol-specified analyses.  
12 
REFERENCES  
1. ICH. ICH Harmonised Tripartite Guideline: Structure and content of clinical study reports (E3). 
30 November 1995.  
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STATISTICAL ANALYSIS PLAN 
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2. ICH. ICH Harmonised Tripartite Guideline: General considerations for clinical trials (E8). 17 
July 1997.  
3. ICH. ICH Harmonised Tripartite Guideline: Statistical principles for clinical trials (E9). 
5 February 1998.  
 
GE-278-001 Statistical Analysis Plan
Version 1.0 Approved  06 Sep 2023


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Date / Name
Justification / Role
Signed By: 
Date of signature: 06-Sep-2023 12:47:07 GMT+0000
Justification: Approved
Role: 
Signed By: 
Date of signature: 06-Sep-2023 15:31:59 GMT+0000
Justification: Approved
Role: 
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Date of signature: 06-Sep-2023 21:56:52 GMT+0000
Justification: Approved
Role: 
Signed By: 
Date of signature: 04-Oct-2023 16:30:47 GMT+0000
Justification: I hereby confirm that this Digital Copy matches
the Physical Source Document
Role: 
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