A Prospective, Non-interventional Study to Collect Subject and Physician Satisfaction During Long Term Treatment of Glabellar Lines With Dysport® in Subjects of Chinese Origin in Real Clinical Practice
Conditions: Glabellar Lines
Sponsor: Galderma R&D

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CLINICAL STUDY PROTOCOL
Clinical Trial Number (CTN): 05PF2009
CONFIDENTIAL
This document contains confidential, proprietary information
All the information provided to the Investigator and his/her staff and all data obtained through this 
Q-Med AB clinical study protocol are confidential. The Sponsor reserves all proprietary rights. No 
information may be disclosed to any third party without
prior written consent from 
Q-Med AB.
  
 
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TITLE PAGE
A Prospective, Non-interventional Study to Collect Subject and Physician Satisfaction During 
Long Term Treatment of Glabellar Lines with Dysport® in Subjects of Chinese Origin in 
Real Clinical Practice
CTN: 05PF2009
SPONSOR
Q-Med AB, part of the Galderma Group
Seminariegatan 21
SE-752 28 Uppsala, Sweden
Phone: +46 18 474 90 00
This clinical study shall be performed in compliance with the clinical trial agreement (CTA), the 
clinical study protocol (CSP), International Council for Harmonisation Good Clinical Practice (ICH
GCP), and applicable regional and national regulations. The study shall be conducted in accordance 
with the ethical principles that have their origin
in the Declaration of Helsinki
(https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-
research-involving-human-subjects/).
  
 
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INVESTIGATOR AND ADMINISTRATIVE STRUCTURE
Role
Contact Information
Investigators:
Approximately 10 study centers. 
Note: Further details on all participating Investigators and the complete administrative structure 
of the study are found in the study files. Note that administrative changes are to be documented in 
the study files without requiring a CSP amendment.
  
 
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PPD
PPD

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TABLE OF CONTENTS
TITLE PAGE..................................................................................................................................................2
INVESTIGATOR AND ADMINISTRATIVE STRUCTURE...................................................................3
TABLE OF CONTENTS...............................................................................................................................4
SYNOPSIS ......................................................................................................................................................8
CLINICAL STUDY SCHEMATIC AND FLOW CHART......................................................................12
SCHEDULE OF ASSESSMENTS..............................................................................................................14
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...........................................................15
1
BACKGROUND AND RATIONALE..............................................................................................16
1.1
Medical Background and Short Rationale for the Clinical Study............................................16
1.2
Drug Profile...................................................................................................................................16
1.3
Risk/Benefit Assessment...............................................................................................................17
2
CLINICAL STUDY OBJECTIVES.................................................................................................18
2.1
Clinical Study Objectives .............................................................................................................18
2.1.1
Primary Efficacy Objectives and Endpoints .........................................................................18
2.1.2
Secondary Efficacy Objectives and Endpoints......................................................................18
3
OVERALL CLINICAL STUDY DESCRIPTION..........................................................................20
4
CLINICAL STUDY DURATION AND TERMINATION ............................................................20
5
SELECTION AND DISPOSITION OF CLINICAL STUDY POPULATION............................21
5.1
Number of Subjects.......................................................................................................................21
5.2
Clinical Study Population Characteristics..................................................................................21
5.2.1
Inclusion Criteria.....................................................................................................................21
5.2.2
Exclusion Criteria....................................................................................................................21
5.3
Medical History.............................................................................................................................22
5.4
Previous and Concomitant Medications and Therapies............................................................22
5.5
Procedures/Reasons for Subject Discontinuation ......................................................................22
6
CLINICAL SUPPLIES......................................................................................................................23
6.1
Clinical Supply Identification and Use........................................................................................23
6.1.1
Product Description.................................................................................................................23
6.1.2
Subject Identification Number (SIN).....................................................................................23
  
 
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6.1.3
Method of Treatment Assignment..........................................................................................24
6.1.4
Randomization Number..........................................................................................................24
6.1.5
Dosage and Administration.....................................................................................................24
6.1.5.1
Post-treatment Care ...........................................................................................................25
6.1.5.2
Treatment Regimen............................................................................................................26
6.2
Product Packaging and Labeling.................................................................................................26
6.3
Supplies Management...................................................................................................................26
6.3.1
Accountability ..........................................................................................................................26
6.3.2
Storage of Study Drug(s).........................................................................................................26
6.3.3
Dispensing and Return ............................................................................................................26
6.3.4
Treatment Compliance Management and Record................................................................26
6.3.5
Product Quality Complaints...................................................................................................26
6.4
Dose Modification .........................................................................................................................27
6.5
Blinding..........................................................................................................................................27
7
EFFICACY ASSESSMENTS ...........................................................................................................28
7.1
Subject Satisfaction Questionnaire..............................................................................................28
7.2
Physician Satisfaction Questionnaire..........................................................................................28
7.3
Subject Self-Assessment of GL Severity .....................................................................................28
7.4
Physician Live Assessment of GL Severity.................................................................................28
8
SAFETY ASSESSMENTS ................................................................................................................30
8.1
Definitions......................................................................................................................................30
8.1.1
Adverse Event (AE) .................................................................................................................30
8.1.2
Adverse Drug Reaction (ADR) ...............................................................................................30
8.1.3
Unexpected Adverse Drug Reaction (UADR) .......................................................................30
8.1.4
Serious Adverse Event (SAE) .................................................................................................30
8.1.5
Special Situation (SS) Events..................................................................................................31
8.2
Severity...........................................................................................................................................31
8.3
Relationship to the Product and/or Procedure...........................................................................31
8.4
Reporting Procedures...................................................................................................................32
8.4.1
Minimum Reporting Criteria .................................................................................................33
8.5
Pregnancy ......................................................................................................................................33
  
 
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8.6
Appropriateness of Measurements..............................................................................................33
9
CLINICAL STUDY VISITS DESCRIPTIONS AND PROCEDURES ........................................35
9.1
Description of Clinical Study Visits.............................................................................................35
9.1.1
Screening (≤ 30 days of Baseline/Injection 1)........................................................................35
9.1.2
Injection Visits / Visits 1, 3 and 5 (3-6 months apart)...........................................................35
9.1.3
Follow up Visits / Visits 2, 4, and 6 (three weeks (± 7 days) from last injection 
visit)...........................................................................................................................................36
9.1.4
Final Follow up Visit / Visit 7 (3-6 months from Visit 5)......................................................36
10
STATISTICAL METHODS PLANNED .........................................................................................37
10.1
Statistical and Analytical Plans ...................................................................................................37
10.1.1
Data Transformations .............................................................................................................37
10.1.2
Populations Analyzed and Evaluability.................................................................................37
10.1.2.1
Enrolled Population............................................................................................................37
10.1.2.2
Per-protocol (PP) Population.............................................................................................37
10.1.3
Withdrawals and Deviations...................................................................................................37
10.1.4
Statistical Methods...................................................................................................................38
10.1.5
Subgroup Analysis ...................................................................................................................38
10.2
Sample Size Determination ..........................................................................................................38
10.3
Analysis..........................................................................................................................................38
11
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE ..............39
11.1
Personnel Training........................................................................................................................39
11.2
Clinical Monitoring.......................................................................................................................39
11.3
Data Management.........................................................................................................................39
11.4
Quality Assurance / Audit / Inspection .......................................................................................39
11.5
Changes in Clinical Study Conduct / Amendments...................................................................40
11.5.1
Clinical Study Conduct............................................................................................................40
11.5.2
Amendments.............................................................................................................................40
12
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS ...................41
12.1
Independent Ethics Committee (IEC).........................................................................................41
12.2
Ethical Conduct of the Clinical Study.........................................................................................41
12.3
Subject Information and Consent ...............................................................................................41
  
 
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12.4
Protection of Personal Data .........................................................................................................41
12.5
Contractual Requirements...........................................................................................................42
12.6
Data Collection and Archiving.....................................................................................................42
12.6.1
Data Collection.........................................................................................................................42
12.6.2
Source Documentation.............................................................................................................42
12.6.3
Archives ....................................................................................................................................43
12.7
Insurance .......................................................................................................................................43
12.8
Publication Policy..........................................................................................................................43
13
LITERATURE REFERENCE LIST................................................................................................45
14
APPENDICES ....................................................................................................................................46
Appendix 1
Subject Satisfaction Questionnaire ...................................................................................47
Appendix 2
Physician Satisfaction Questionnaire................................................................................50
Appendix 3
Subject Self-Assessment of GL Severity using the 4-point Categorical Scale...............52
15
SIGNED AGREEMENT OF THE CLINCAL STUDY PROTOCOL..........................................58
List of Tables
Table 1
Clinical Study Schematic...........................................................................................................12
Table 2
Schedule of Assessments...........................................................................................................14
Table 3
Description and Usage of the Study Drug .................................................................................23
Table 4
4-point Categorical Scale of GL Severity..................................................................................28
List of Figures
Figure 1 
Study Flow Chart.......................................................................................................................13
Figure 2 
Injection Sites for Treating Glabellar Lines...............................................................................25
  
 
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SYNOPSIS
Clinical Study Title: A Prospective, Non-interventional Study to Collect Subject and Physician Satisfaction During 
Long Term Treatment of Glabellar Lines with Dysport in Subjects of Chinese Origin in Real Clinical Practice
Clinical Study Phase:
Post-marketing study
Clinical Study Population: Male and female adult subjects up to 65 years of age with moderate to severe glabellar 
lines (GL).
Clinical Study Design:
This is a prospective, longitudinal, non-interventional, multi-center study to collect 
subject and physician satisfaction, and treatment experience with Dysport in real clinical 
practice in subjects of Chinese origin.
Approximately 250 subjects are planned to be included in the study to receive three 
injection cycles with Dysport in the GL. The decision by the physician to treat the 
subject with Dysport on a long term basis must be made before including the subject in 
the study, and has to be clearly separated and independent of the decision to include the 
subject in the study.
Given the non-interventional nature of the study, subject visits, treatment regimen, and 
the administration of Dysport to treat GL will be carried out according to the physician’s 
real clinical practice and the approved leaflet in China.
The study consists of three injection cycles. Each injection cycle includes an injection 
visit and a follow up visit three weeks later (± 7 days). Following the 1st injection at 
Visit 1, subsequent injections, i.e., 2nd injection and 3rd injection, will be scheduled three 
to six months apart. The final follow up visit will be held three to six months after the 
subject’s 3rd injection. 
The screening visit and the 1st injection visit may be conducted on the same day. Data 
will be collected at all visits, if held. Subjects and physicians, independent of each other,
will assess the subject’s GL severity, and will complete a questionnaire about
satisfaction with treatment outcomes at all visits. 
Injection practice details for each injection visit, including muscle(s) injected, total dose 
and volume, dose and volume per injection point, and number of injection points will be 
collected per the study objectives. 
Adverse events (AEs) will be collected during the study. 
Total Number of Subjects 
(Planned): 
Approximately 250 subjects will be included in the study. 
To avoid bias in the recruitment of subjects, physician will be asked to include all
consecutive subjects during Botulinum toxin A (BoNT-A) consultations to achieve the 
recruitment target of 20-30 subjects during a restricted and defined period. If consecutive 
inclusions are not feasible (e.g., administrative constraints), and in order not to disturb 
the medical activities in the physician’s clinic, physician will be authorized to space the 
inclusions (e.g. inclusion of one subject after every two, or three, etc.), and will follow 
the same recruitment frequency until achievement of the recruitment target. The 
modalities for recruitment will have to be determined prior to recruitment start.
Number of Clinical Study 
Centers (Planned):
10 study centers
  
 
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Region(s) / Country 
Involved (Planned):
China
Clinical Study Duration:
The planned clinical study duration is approximately 24 months. 
The planned duration of recruitment is approximately six months.
Duration of Subject 
Participation: 
In accordance with the treatment regimen and the physician’s real clinical practice, study 
participation for each subject is anticipated to be approximately nine to 18 months.
Inclusion Criteria:
1.
Adult male or female up to 65 years of age, and of Chinese origin.
2.
Moderate (grade 2) or severe (grade 3) glabellar lines at max frown as assessed 
by the physician using the 
3.
Prior to and independent of study, subject is seeking long term treatment of 
their glabellar lines. 
4.
Prior to and independent of the study participation, physician intended to treat 
the subject with Dysport.
5.
Time and ability to complete the study and comply with instructions.
6.
Understands the study requirements and signed the informed consent form 
(ICF).
Exclusion Criteria
1.
Hypersensitive to Dysport or its excipients.
2.
Presence of contraindications to Dysport treatment as specified in the approved 
leaflet in China.
3.
Subject is at risk for precautions, warnings, and/or contraindications to Dysport
as specified in the approved leaflet in China
4.
Subject has an infection in the proposed treatment area.
5.
Subjects has had treatment failure experience with other toxins. 
6.
Pregnant or breast feeding female, or female intending to get pregnant during 
the study.
7.
Participation in a clinical study, interventional or non-interventional, within 30 
days prior to study entry (signature of informed consent). 
Treatment:
This is a non-interventional study (NIS). The decision by the physician to treat the 
subject with Dysport on a long term basis must be made before including the subject in 
the study, and has to be clearly separated and independent of the decision to include the 
subject in the study. 
Commercially available Dysport will be used in the study but will not be supplied by 
the study Sponsor. The physician is free to choose Dysport modalities of administration 
in accordance with the local SmPC and the approved leaflet in China.
  
 
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Product:
Commercially available Dysport, a BoNT-A product.
Strength/Concentration: 300 units (U) per vial
Reconstitution Volume:
1.5 milliliter (mL)
Dosage (total dose per 
treatment):
50 U total (0.25 mL total)
10 U per injection site (0.05 mL per injection site)
Route:
Intramuscular injection
Treatment Regimen:
Three injection cycles, 3-6 months apart
Location of Treated 
Area:
Glabellar region
Efficacy Assessments:
Efficacy assessments include:

Subject Satisfaction Questionnaire

Subject assessment of GL severity at max frown using the 4-point Categorical 
Scale

Physician Satisfaction Questionnaire

Physician assessment of GL severity at rest and max frown using the 
Investigator’s 4-point Photographic Scale

Injection practice details
Primary Objective and 
Endpoint:
The primary objective of the study is to evaluate subject satisfaction after three injection 
cycles with Dysport in the GL.
At Visit 6 (i.e., three weeks, ± 7 days, after the 3rd injection) subjects will be asked “What 
is your overall satisfaction after three treatment cycles with Dysport?” See Appendix 1
Question 17.
Response options:

Very Satisfied

Satisfied

Dissatisfied

Very Dissatisfied
The primary endpoint will evaluate the proportion of subjects in each response category. 
Secondary Objectives and 
Endpoints:
The secondary efficacy objectives and endpoints of the study are:
1.
Objective: To evaluate physician satisfaction after three injection cycles with 
Dysport in the GL.
Endpoint: Proportion of subjects in each response category for the physician’s 
overall satisfaction with Dysport after three injection cycles will be evaluated at 
Visit 6 (i.e., three weeks, ± 7 days, after the 3rd injection). See Appendix 2, Question 
7.
2.
Objective: To evaluate subject 
 after each injection cycle 
with Dysport in the GL.
Endpoints: 
a. Proportion of subjects in each response category per question answered on 
the Subject Satisfaction Questionnaire complete at all visits. See Appendix 
1.
  
 
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Safety Assessment:
AEs will be collected during the study. AE data will be recorded in the electronic case 
report form (eCRF) for inclusion in the clinical database. 
In addition to AEs, physicians will report any Adverse Drug Reaction (ADR), 
Unexpected ADR (UADR), Serious Adverse Event (SAE), Special Situation (SS) and 
pregnancy events to 
 in accordance with regulatory 
requirements and timelines. The data will be included in the global drug safety database.
Statistical Methods:
In general, efficacy, safety, and baseline characteristics variables will be presented using 
descriptive statistics and graphs, as appropriate. Continuous endpoints will be 
summarized using descriptive statistics (e.g., mean, median, standard deviation, 
minimum and maximum values). Categorical endpoints will be presented in frequency 
tables with number and percentage of observations for each level.
95% confidence intervals (CIs) will be calculated whenever appropriate.
Sample Size:
The sample size of approximately 250 subjects is not based on a statistical calculation. 
The selected number of subjects is regarded as sufficient for an evaluation of the studied 
endpoints by using descriptive statistics.
Analysis:
Since this is an open non-interventional study, available data may be analyzed prior to 
study completion.
  
 
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CLINICAL STUDY SCHEMATIC AND FLOW CHART
Table 1
Clinical Study Schematic
Physician decision to treat the subject with Dysport on a long term basis

Screening/Baseline/1st Injection

Treatment 
Commercially available Dysport
Treatment Frequency
Three injection visits, three to six months apart 
(Visits 1, 3, 5)

Follow up Visits
A follow up visit occurs three weeks (± 7 days) after each injection visit
(Visits 2, 4, 6)
Final follow up visit occurs three to six months after the 3rd injection
(Visit 7)
  
 
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Figure 1
Study Flow Chart
  
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Term
C
Degrees Celsius
ADR
Adverse Drug Reaction
AE
Adverse Event
BoNT
Botulinum toxin
BoNT-A
Botulinum toxin serotype A
CI
Confidence interval
eCRF
electronic Case Report Forms
CRO
Contract Research Organization
CSP
Clinical Study Protocol
CTA
Clinical Trial Agreement
e.g. 
For Example (Latin: exempli gratia)
etc.
Et cetera
G
Gauge
GL
Glabellar lines
GCP 
Good Clinical Practice 
HSA
human serum albumin
ICH
International Council for Harmonisation
i.e. 
That is (Latin: id est)
IEC
Independent Ethics Committee
ICF
Informed Consent Form
mL
Milliliter
N/A
Not Applicable
NIS
Non-interventional study
NMPA
National Medical Products Administration 
p
Page(s)
PP
Per-Protocol
PQC
Product Quality Complaint
QA
Quality Assurance
RA
Regulatory Authority
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SS
Special Situation
U
Units
UADR
Unexpected Adverse Drug Reaction
Note: Physician and Investigator are synonymous and used interchangeably throughout the CSP.
  
 
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1
BACKGROUND AND RATIONALE
1.1
Medical Background and Short Rationale for the Clinical Study
Botulinum toxin (BoNT) is a potent neurotoxic protein produced by the Gram-positive anaerobic 
bacterium, Clostridium botulinum. The molecule is produced naturally by these bacteria together 
with a series of accessory proteins, forming what is termed the “toxin complex”. The neurotoxin is 
the cause of the severe and potentially fatal disease of botulism. In addition, the protein is used in 
very small quantities as a treatment modality for aesthetic and medical indications, many of which 
are characterized by increased muscle activity. Botulinum toxins occur in seven known serotypes 
(A-G) that are produced by different strains of Clostridium botulinum. Clinically important biologic 
activity is limited primarily to the A and B serotypes, of which the type A serotype (BoNT-A) is 
used widely throughout the world for the treatment of a range of clinical conditions. BoNT-A blocks 
the release of acetylcholine into the neuromuscular junction (synapse) cleft, thereby prohibiting the 
activation of acetylcholine receptors. Paresis by chemical denervation thus occurs in the target 
muscle, leading to inhibition of muscular contraction.
In the early 1990s, patients treated with BoNT-A for blepharospasm were observed to lose their 
frown lines,1, 2 and since publishing these observations, the use of BoNT-A in the aesthetic setting 
has accelerated. Injectable BoNT-A products have been investigated for multiple aesthetic 
indications in attempts to reverse the appearance of aging, especially in the facial region.1 In the 
treatment of facial lines, the effect of BoNT-A injections usually persists for approximately 
4-6 months. Facial muscle activity and severity of the facial wrinkles then returns to baseline. Full 
functionality of facial muscles is usually restored by approximately 6 months post-treatment.3
Ipsen is the marketing holder of Dysport, a BoNT-A product, which is currently licensed in over 
75 countries worldwide, and it was approved by the National Medical Products Administration of 
China (NMPA) in 2020. It is indicated for the temporary improvement in the appearance of moderate 
to severe glabellar lines (GL) caused by the activity of corrugator or musculus procerus in adult 
patients not more than 65 years of age. To achieve a clinical effect, a total of 50 units (U) is given 
intramuscularly in five equal aliquots of 10 U each into each of five sites, two in each corrugator 
muscle and one in the procerus muscle. Re-treatments should be administered no more frequently 
than every three months. 
Controlled clinical trials in China demonstrated the short and long term efficacy and safety of 
Dysport in the treatment of the GL; however, there is a lack of scientific data related to subject and 
physician reported outcomes. The rationale for the current study is to collect subject and physician 
satisfaction, and long term treatment experience with Dysport in the GL in subjects of Chinese origin
in a real-life clinical setting. 
1.2
Drug Profile
Dysport contains a neurotoxin complex that is produced by fermentation of Clostridium botulinum 
bacteria toxin type A, Hall strain. This haemagglutinin complex is composed of a number of proteins 
naturally produced along with the toxin which is believed to stabilize it but which has no apparent 
therapeutic effect in its own right. Dysport contains nominally 300 U of BoNT-A-haemagglutinin 
  
 
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Page 17 of 58
complex 
together 
with 
125 
μg 
of 
human 
serum 
albumin 
(HSA) 
and 
2.5 mg of lactose in a clear glass vial. Further details can be found in the approved leaflet in China.4
Dysport is labelled for a dose of 50 U to be injected intramuscularly in five equal aliquots of 
10 U each into each of five sites, two in each corrugator muscle and one in the procerus muscle.
Retreatment is permitted every three months.4
1.3
Risk/Benefit Assessment
In placebo-controlled clinical trials of Dysport, very common adverse reactions (> 1/10) following 
injection were injection site reactions (e.g. erythema, oedema, irritation, rash, pruritus, paraesthesia, 
pain, discomfort, stinging and haematoma), and headache. Common reactions (> 1/100) included 
eye disorders (e.g., asthenopia, eyelid ptosis, eyelid oedema, lacrimation increased, dry eye, muscle
twitching (twitching of muscles around the eyes), and facial paresis (due to temporary paresis of
facial muscles proximal to injection sites, it is predominantly manifested as brow paresis).4
Side effects related to spread of toxin distant from the site of administration have been reported, 
such as dry mouth, excessive muscle weakness, dysphagia, aspiration pneumonia, with fatal 
outcome in some very rare cases. Hypersensitivity reactions have also been reported post-marketing.
4
The dose administered and the minimum time between treatments are according to the approved 
leaflet in China. Steps to reduce complications of ptosis are outlined in Section 6.1.5. Subject will 
be provided with information on the benefits and risks of their treatment by the physician in 
accordance with their real clinical practice.
The risks associated with participation in this study are considered acceptable compared to the 
anticipated high degree of subject and physician satisfaction with treatment and the treatment 
regimen. 
  
 
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2
CLINICAL STUDY OBJECTIVES 
2.1
Clinical Study Objectives
The objectives of this study are to collect subject and physician satisfaction, and long term treatment 
experience with Dysport in the GL in subjects of Chinese origin in a real-life clinical setting.
2.1.1
Primary Efficacy Objectives and Endpoints
The primary objective of the study is to evaluate subject satisfaction after three injection cycles with 
Dysport in the GL.
At Visit 6 (i.e., three weeks, ± 7 days, after the 3rd injection) subjects will be asked “What is your 
overall satisfaction after three treatments cycles with Dysport?” See Appendix 1, Question 17.
Response options:

Very Satisfied

Satisfied

Dissatisfied

Very Dissatisfied
The primary endpoint will evaluate the proportion of subjects in each response category.
2.1.2
Secondary Efficacy Objectives and Endpoints
The secondary efficacy objectives and endpoints of the study are:
1. Objective: To evaluate physician satisfaction after three injection cycles with Dysport in the GL. 
Endpoint: Proportion of subjects in each response category for the physician’s overall 
satisfaction with Dysport after three injection cycles will be evaluated at Visit 6 (i.e., three 
weeks, ± 7 days, after the 3rd injection). See Appendix 2, Question 7. 
2. Objective: To evaluate subject 
 after each injection cycle with Dysport
in the GL.
Endpoints: 
a.
Proportion of subjects in each response category per question answered on the Subject 
Satisfaction Questionnaire complete at all visits  See Appendix 1
  
 
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3
OVERALL CLINICAL STUDY DESCRIPTION
This is a prospective, longitudinal, non-interventional, multi-center study to collect subject and 
physician satisfaction, and treatment experience with Dysport in real clinical practice in subjects of 
Chinese origin. 
Approximately 250 subjects are planned to be included in the study to receive three injection cycles 
with Dysport in the GL. The decision by the physician to treat the subject with Dysport on a long
term basis must be made before including the subject in the study, and has to be clearly separated 
and independent of the decision to include the subject in the study.
Given the non-interventional nature of the study, subject visits, treatment regimen, and the 
administration of Dysport to treat GL will be carried out according to the physician’s real clinical 
practice and the approved leaflet in China. 
The study consists of three injection cycles. Each injection cycle includes an injection visit and a 
follow up visit three weeks later (± 7 days). Following the 1st injection at Visit 1, subsequent 
injections, i.e., 2nd injection and 3rd injection, will be scheduled three to six months apart. The final
follow up visit will be held three to six months after the subject’s 3rd injection. 
The screening visit and the 1st injection visit may be conducted on the same day. Data will be 
collected at all visits, if held. Subjects and physicians, independent of each other, will assess the 
subject’s GL severity, and will complete a questionnaire about satisfaction with treatment outcomes 
at all visits. 
Injection practice details for each injection visit, including muscle(s) injected, total dose and volume, 
dose and volume per injection point, and number of injection points will be collected per the study 
objectives. 
Adverse events (AEs) will be collected during the study. 
4
CLINICAL STUDY DURATION AND TERMINATION
The planned clinical study duration is approximately 24 months. The date of end of the clinical study
is defined as the date of the last visit of the last subject.
The planned duration of recruitment is approximately six months.
In accordance with the treatment regimen and the physician’s real clinical practice, study
participation for each subject is anticipated to be approximately nine to 18 months.
The Sponsor may decide to prematurely terminate or suspend the participation of a particular clinical 
study center (for example, for lack of subject enrollment or non-compliance with clinical study
protocol, regulation, or GCP) or prematurely suspend the clinical study (for example, for safety, 
study drug(s) quality, regulatory, efficacy, or logistical reasons) at any time with appropriate 
notification.
  
 
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5
SELECTION AND DISPOSITION OF CLINICAL STUDY POPULATION
5.1
Number of Subjects
Approximately 250 subjects will be included in the study. 
To avoid bias in the recruitment of subjects, physician will be asked to include all consecutive 
subjects during Botulinum toxin A (BoNT-A) consultations to achieve the recruitment target of 20-
30 subjects during a restricted and defined period. If consecutive inclusions are not feasible (e.g., 
administrative constraints), and in order not to disturb the medical activities in the physician’s clinic, 
physician will be authorized to space the inclusions (e.g. inclusion of one subject after every two, or 
three, etc.), and will follow the same recruitment frequency until achievement of the recruitment 
target. The modalities for recruitment will have to be determined prior to recruitment start.
5.2
Clinical Study Population Characteristics
In order to be eligible for the clinical study, subjects must fulfill all of the following criteria. These 
criteria are applicable at screening/baseline. 
5.2.1
Inclusion Criteria
1.
Adult male or female up to 65 years of age, and of Chinese origin. 
2.
Moderate (grade 2) or severe (grade 3) glabellar lines at max frown as assessed by the 
physician
3.
Prior to and independent of study, subject is seeking long term treatment of their glabellar 
lines. 
4.
Prior to and independent of the study participation, physician intended to treat the subject with 
Dysport.
5.
Time and ability to complete the study and comply with instructions.
6.
Understands the study requirements and signed the informed consent form (ICF).
5.2.2
Exclusion Criteria
1.
Hypersensitive to Dysport or its excipients.
2.
Presence of contraindications to Dysport treatment as specified in the approved leaflet in 
China.
3.
Subject is at risk for precautions, warnings, and/or contraindications to Dysport as specified in 
the approved leaflet in China.
4.
Subject has an infection in the proposed treatment area.
  
 
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5.
Subjects has had treatment failure experience with other toxins. 
6.
Pregnant or breast feeding female, or female intending to get pregnant during the study.
7.
Participation in a clinical trial, interventional or non-interventional, within 30 days prior to 
study entry (signature of informed consent). 
5.3
Medical History
Relevant history of surgical events and medical conditions shall be documented using medical 
terminology according to the physician’s real clinical practice. 
5.4
Previous and Concomitant Medications and Therapies
Previous and concomitant medications and therapies shall be documented using medical 
terminology according to the physician’s real clinical practice. 
5.5
Procedures/Reasons for Subject Discontinuation
The importance of completing the entire clinical study should be explained to the subject by the 
clinical study personnel; however, any subject is free to discontinue participation in this clinical 
study at any time and for whatever reason, specified or unspecified, and without any prejudice. No 
constraints are to be imposed on the subject, and when appropriate, a subject may be treated with 
other conventional therapy.
  
 
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6
CLINICAL SUPPLIES
Commercially available Dysport will be used in the study but will not be supplied by the study 
Sponsor per the non-interventional nature of the study.
6.1
Clinical Supply Identification and Use
Dysport is a white lyophilised powder provided in a vial containing 300 U botulinum toxin type A
hemagglutinin complex, 125 μg human serum albumin, and 2.5 mg of lactose. Each vial will be 
reconstituted with 0.9% sodium chloride for injection to yield a solution containing 200 U
per mL. A total volume of 0.25 mL of reconstituted Dysport will be administered in 5 equal aliquots 
of 0.05 mL each.
The product should be stored at the recommended temperature (between 2°C and 8°C). The product 
does not contain any antimicrobial agent. Therefore, it is recommended that the product is used 
immediately after reconstitution. It should not be frozen and should be protected from light.
6.1.1
Product Description
Table 3
Description and Usage of the Study Drug
Product
Trade Name
Dysport 
Name of Drug Substance
abobotulinumtoxinA
Internal Code
N/A
Pharmaceutical Form
Lyophilised powder
Strength
300 U per vial
Packaging
Single-use vial for reconstitution with 1.5 mL 0.9% Sodium Chloride Injection
Storage conditions
2-8ºC
Reconstitution volume
1.5 mL
Dosage
50 U total (0.25 mL total)
10 U per injection site (0.05 mL per injection site)
Route
Intramuscular injection
Dose regimen 
Up to three treatment cycles, 3-6 months apart
Location of treated area
Glabellar region
6.1.2
Subject Identification Number (SIN) 
Each study participant who has signed the ICF will be entered into the electronic Case Report Forms
(eCRF) system and a subject number will be assigned via the eCRF system. Subject numbers will 
consist of the study center number followed by a consecutive number starting with 001 at each 
center. The subject numbers shall be allocated in ascending sequential order within each center. The 
reason for excluding a consenting subject from entering the study should be specified in each case. 
A screen failure should not be re-screened in the study.
  
 
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All subjects who have signed the ICF should be listed. Sufficient information to link the eCRF to 
the medical records should be recorded in the source documentation. 
For the duration of the entire study, the subject will be identified using the subject number for all 
documentation and discussion.
6.1.3
Method of Treatment Assignment
Not applicable; this is a non-interventional study.
6.1.4
Randomization Number
Not applicable; this is a non-interventional study.
6.1.5
Dosage and Administration 
This is a non-interventional study. The decision by the physician to treat the subject with Dysport 
on a long term bases must be made before including the subject in the study. The physician is free 
to choose Dysport modalities of administration in accordance with the approved leaflet in China.4
The units of Botulinum Toxin Type A are specific to the preparation and are not interchangeable 
with other preparations of botulinum toxin.
Botulinum Toxin Type A must be administered by appropriately qualified physicians with relevant 
professional knowledge and skills.
When preparing and handling Botulinum Toxin Type A solutions, the use of gloves is recommended. 
If Botulinum Toxin Type A dry powder or reconstituted solution should come into contact with the 
skin or mucous membranes, they should be washed thoroughly with water.
Dysport is supplied as a single-use vial. Each vial is intended for one treatment administration 
session for a single subject. When reconstituting the product, the exposed central portion of the 
rubber stopper should be cleaned with alcohol immediately prior to piercing the septum. A sterile 
23 gauge (G) or 25 G needle should be used. The product should be reconstituted with 1.5 mL of 
sodium chloride injection (0.9%) to yield a solution containing 200 U per mL. Appearance of 
product after reconstitution: A clear, colorless solution, free from particulate matter.
Prior to injection, remove any make-up and disinfect the skin with a local antiseptic.
Before injection, place the thumb or index finger firmly below the orbital rim in order to prevent 
extravasation below the orbital rim. The needle should be pointed upward and medially during the 
injection. 
In order to reduce the complication of ptosis, the following steps should be taken: 

Avoid injections near the levator palpebrae superioris muscle, particularly in patients with 
larger depressor supercilii. 
  
 
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
Injections in the corrugator muscle must be made into the central part of that muscle, at least 
1 cm above the orbital rim.
The recommended dose is 50 U (0.25 mL of reconstituted solution) of Dysport divided into 
five injection sites, 10 U (0.05 mL of reconstituted solution) administered intramuscularly, at right 
angles to the skin, into each of the five sites: two injections into each corrugator muscle and one 
into the procerus muscle near the nasofrontal angle as shown in Figure 2. Intramuscular injections 
performed with a sterile 29-30 G needle.
Figure 2
Injection Sites for Treating Glabellar Lines
1. Procerus    2. Corrugator   3. Lateral Corrugator/Orbicularis
Immediately after treatment of the patient, any residual Dysport which may be present in either vial 
or syringe should be inactivated with dilute hypochlorite solution (1% available chlorine).
Spillage of Dysport should be wiped up with an absorbent cloth soaked in dilute hypochlorite 
solution.
Any unused product or waste material should be disposed of in accordance with local requirements.
Discard needle and syringe in accordance with local regulations.
6.1.5.1
Post-treatment Care
Subjects should be provided with post-treatment care instructions per the physician’s real clinical 
practice. 
  
 
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6.1.5.2
Treatment Regimen
The treatment regimen will be performed according to the approved leaflet in China and the 
physician’s real clinical practice. Each enrolled subject will receive treatment with Dysport in the 
GL at Visits 1, 3, and 5, scheduled three to six months apart. 
6.2
Product Packaging and Labeling
Commercially available Dysport will be used in the study.
6.3
Supplies Management
6.3.1
Accountability
Commercially available Dysport will be used in the study. The physician is responsible for suppling 
the product used in the study, and accountability should be documented according to the physician’s 
real clinical practice.
6.3.2
Storage of Study Drug(s)
Dysport should be stored in accordance with the approved leaflet in China.
6.3.3
Dispensing and Return 
Not applicable; this is a non-interventional study.
6.3.4
Treatment Compliance Management and Record
This is a non-interventional study. The decision by the physician to treat the subject with Dysport 
on a long term bases must be made before including the subject in the study. The physician is free 
to choose Dysport modalities of administration in accordance with the approved leaflet in China.
The treatment is an injection administered by the physician. Injection practice details for each 
injection visit, including muscle(s) injected, total dose and volume, dose and volume per injection 
point, and number of injection points will be collected per the study objectives. 
6.3.5
Product Quality Complaints
Product Quality Complaints (PQCs) should be reported to 
A PQC is 
an external judgement presuming a quality defect of a product; quality issue for a product relating 
to its presentation or use, identified by a subject, a practitioner, physician, or study center personnel, 
a distributor, or anyone else involved in clinical supplies handling. Examples may include but are 
not limited to appearance issues, odor, damaged stoppers, low fills, and foreign matter in the product. 
These complaints may or may not represent a potential risk to the subject. A PQC should be clearly 
  
 
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described in an email submitted by the study center personnel to 
 within 24 hours of 
awareness. Affected study product should be quarantined, and not used, until further notice by the 
 
See Investigator and Administrative Structure for additional contact details. 
In addition to submitting the PQC, any subject reaction associated with a PQC should be documented 
and evaluated by the physician according to Section 8. 
6.4
Dose Modification 
Per real clinical practice, the physician is to administration Dysport in accordance with the approved 
leaflet in China.4
6.5
Blinding
Not applicable; this is a non-interventional study. 
  
 
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7
EFFICACY ASSESSMENTS 
7.1
Subject Satisfaction Questionnaire
Subjects will be asked to complete the Subject Satisfaction Questionnaire, all or in part as specified,
at all study visits, prior to treatment, as applicable (Appendix 1). The subject should complete the 
questionnaire independent of the physician.
7.2
Physician Satisfaction Questionnaire
Physicians will complete the Physician Satisfaction Questionnaire, all or in part as specified, at all 
study visits, prior to treatment, as applicable (Appendix 2). The physician should complete the 
questionnaire independent of the subject. 
7.3
Subject Self-Assessment of GL Severity 
Subjects will evaluate the appearance of their glabellar lines at max frown using a 4-point 
Categorical Scale. The 4-point Categorical Scale represents the severity of glabellar lines from no 
wrinkles (grade 0) to severe wrinkles (grade 3) as represented in Table 4.
The subject self-assessment of GL severity will be complete at all study visits, prior to treatment, as 
applicable, and should be made independently of the physician’s assessment. See Appendix 3 for 
additional details and subject instructions. 
Table 4
4-point Categorical Scale of GL Severity
Grade
Severity of Glabellar Lines
0
No wrinkles
1
Mild wrinkles
2
Moderate wrinkles
3
Severe wrinkles
With guidance from the physician, subjects may also reference the 
 
) when completing their self-assessment. 
7.4
Physician Live Assessment of GL Severity 
Physicians will use the 
 for direct, live 
comparison of the severity of the subject’s glabellar lines at rest and max frown at all study visits, 
prior to treatment, as applicable.
The 
 includes two grading systems: one for the 
assessments at rest, and one for the assessments at max frown. The scale represents the severity of 
glabellar lines from none (grade 0), mild (grade 1), moderate (grade 2) to severe (grade 3). Each 
grade is also depicted by an individual photograph and a descriptive text.
  
 
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Physicians will be trained on the use of the scale, and the assessment of GL severity at rest should 
be performed before the assessment at max frown. See Appendix 4 for physician instructions and 
 
  
 
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8
SAFETY ASSESSMENTS 
AEs will be recorded in the eCRF for inclusion in the clinical database. 
In addition, physicians will report all AEs non-serious, serious, and/or unexpected ADRs, and SS
events to 
in accordance with regulatory reporting requirements 
and timelines. The data will be included in the global drug safety database.
8.1
Definitions 
8.1.1
Adverse Event (AE)
Any untoward medical occurrence in a patient or clinical investigation subject administered a
pharmaceutical product and which does not necessarily 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 a medicinal product, whether or 
not related to the medicinal product.
Thus, any new sign, symptom or disease, or any clinically significant worsening of an existing sign, 
symptom or disease (including new episodes of a chronic disease) compared to the condition at the 
first visit, should be considered as an AE.
8.1.2
Adverse Drug Reaction (ADR)
For marketed medicinal products, an ADR is a response to a drug which is noxious and unintended 
and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases
or for modifications of physiological function.
8.1.3
Unexpected Adverse Drug Reaction (UADR)
An unexpected ADR is defined as an adverse reaction, the nature or severity of which is not 
consistent with the applicable study product information (e.g., medicinal package insert/summary 
of product characteristics for an approved study product).
8.1.4
Serious Adverse Event (SAE)
A SAE is any untoward medical occurrence that at any dose:

Results in death,

Is life-threatening,

Requires inpatient hospitalization or prolongation of existing hospitalization,

Results in persistent or significant disability/incapacity, or
  
 
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
Is a congenital anomaly/birth defect.
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered a SAE when, based upon appropriate medical judgment, they may jeopardize the 
safety of the subject, and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. Examples of such events are intensive treatment in an emergency room or 
at home for allergic bronchospasm, blood dyscrasia, or convulsions that do not result in 
hospitalization.
Note: The term “life-threatening” 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.
In-patient hospitalization is considered to have occurred if the subject had to stay for a night at the 
hospital. The criterion for prolongation of hospitalization is also defined as an extra night at the 
hospital. Hospitalization solely for the purpose of a diagnostic test, even if related to an AE, elective 
hospitalization for an intervention which was already planned before subject enrolment in the 
clinical study, admission to a day care facility, social admission (e.g., if the subject has no place to 
sleep), or an administrative admission (e.g., for an annual physical examination) may not itself 
constitutes sufficient grounds to be considered as SAE.
8.1.5
Special Situation (SS) Events
A Special Situation (SS) event is an incidence of overdose, off-label use, medication error, 
occupational exposure, abuse, misuse or lack of therapeutic efficacy while using the medicinal 
product, or any instance of drug exposure during pregnancy or breast-feeding. A SS should be 
reported even if it is not associated with an adverse event.
8.2
Severity
Severity is a clinical determination of the intensity of an AE and not the severity of a disease.
The physician is to classify the intensity of AEs using the following definitions as a guideline. For 
this classification, the physician will take into account the possible range of the intensity of the event 
and report the grade of intensity which is the most appropriate according to his/her medical 
judgment.
Mild
Awareness of signs or symptom, but easily tolerated.
Moderate
Discomfort, enough to cause interference with usual activity.
Severe
Incapacitating with inability to work or perform usual activity.
8.3
Relationship to the Product and/or Procedure
The physician is to determine whether there is a reasonable causal relationship between the 
occurrence of the reaction and exposure to the product and/or the injection procedure.
  
 
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Medical judgment should be used to determine the relationship, considering all relevant factors 
including the pattern of reaction, temporal relationships, relevant medical history, and confounding 
factors such as co-medication or concurrent diseases.
The expression “reasonable causal relationship” is meant to convey in general that there are facts or 
arguments to suggest a causal relationship (ICH E2A, Section IIIA 1).
The relationship assessment for a reaction is to be completed using the following definitions as a 
guidelines.
Reasonable Possibility:
According to the reporting physician, there is a reasonable possibility (i.e., suggestive evidence or 
arguments) that there is a causal relationship irrespective of the dose administered between:

The product and the reaction.

The injection procedure (injection related trauma, etc.) and the reaction. 
A two-point scale (Yes or No response) shall be used for the causality assessment. 

“Do you consider that there is a reasonable possibility that the reaction may have been caused 
by the product?”, and 

“Do you consider that there is a reasonable possibility that the reaction may have been caused 
by the injection procedure?”
If either of these questions is answered Yes, the reaction is considered related, and should be reported 
according to the procedures outlined in Section 8.4. 
No Reasonable Possibility:
No suggestive evidence or arguments can be identified regarding a causal relationship between the 
product or the procedure and the reaction.
8.4
Reporting Procedures
AE data will be recorded in the eCRF for inclusion in the clinical database and will be reported to
. 
In addition, any ADR/UADR/SAE/SS and pregnancy must be reported immediately (within 
24 hours of the physician’s knowledge of the event) to the following:
See Investigator and Administrative Structure for additional contact information. 
In order to facilitate this reporting, the physicians will be provided with Adverse Event and Special 
Situation Reporting Form If the immediate report is submitted by telephone, this must be followed 
by detailed written reports using the Adverse Event and Special Situation Reporting Form .
  
 
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8.4.1
Minimum Reporting Criteria
The following information is the minimum that must be provided to the pharmacovigilance contact 
within 24 hours of being aware of such adverse reactions:

Subject identifier

Product

AE term and description

Physician name and contact details
Any additional information included in the Adverse Event and Special Situation Reporting Form 
must be provided as soon as it is available. 
The physician should report a diagnosis or a syndrome rather than individual signs or symptoms. 
The physician should also try to separate a primary AE considered as the foremost untoward medical 
occurrence from secondary AE which occurred as complications.
8.5
Pregnancy
Pregnancy itself is not regarded as an adverse reaction unless there is a suspicion that the product 
has interfered with a contraceptive method. If pregnancy occurs while using the product, the 
outcome of the pregnancy will then need to be collected. This applies to whether or not the 
pregnancy is considered to be related to interference of the product with a contraceptive method.
Any pregnancy complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.
Abnormal pregnancy outcomes (e.g. spontaneous abortion, foetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such.
Information regarding pregnancies must be manually collected on the Drug Exposure for Pregnancy 
Form, item 1 to 19.
Outcome information should also be collected on the Drug Exposure for Pregnancy Form, item 20 
to 29. Drug Exposure for Pregnancy Form must be reported to 
 
immediately (within 24 hours of the physician’s knowledge of the event).
The physician must instruct all female subjects to inform them immediately should they become 
pregnant while using the product. The physician should counsel the subject, discussing the risks of 
continuing with the pregnancy and the possible effects on the fetus. 
8.6
Appropriateness of Measurements
The satisfaction questionnaires are tools that have been developed in order for the Sponsor to better 
understand the subject and physician needs and expectations with respect to Dysport treatment and 
the treatment regimen.
  
 
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10
STATISTICAL METHODS PLANNED
10.1
Statistical and Analytical Plans
A Statistical Analysis Plan (SAP) will be developed as a separate document. The SAP will contain 
a more detailed and technical description of specific data conventions, calculations and of statistical 
procedures for executing the analyses that are specified in the sections of the clinical study protocol 
below. The SAP will be finalized prior to FSFV.
Any change made to the finalized SAP will be documented in the Clinical Study Report (CSR).
10.1.1
Data Transformations
Not applicable. 
10.1.2
Populations Analyzed and Evaluability 
The primary analysis will be performed on the enrolled population. Analysis on the per-protocol 
(PP) population maybe performed, if needed.
The rules for the allocation of subjects to each of the analysis populations will be defined and 
documented during a data review meeting held prior to database lock.
During the data review meeting, based on minor or major protocol deviations recorded, subjects may 
be excluded from the PP population.
Subjects may be excluded from the analyses if one or more of the following deviations occur. 

Subject did not complete the study

Violation of inclusion/exclusion criteria
10.1.2.1
Enrolled Population
The enrolled population includes all subjects who are enrolled in the study treated at least once with
Dysport.
10.1.2.2
Per-protocol (PP) Population
The Per Protocol (PP) population is a subset of the enrolled subjects who have no major protocol 
deviations, as outlined above.
10.1.3
Withdrawals and Deviations
All withdrawn subjects will be listed individually, including at least subject number, date and reason 
for withdrawal, and last visit performed.
  
 
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Subjects with CSP deviations will be listed individually, including subject number and observed 
deviation. Depending on the seriousness of the deviation, the subject might be excluded from the PP 
population, which shall be documented prior to database lock.
10.1.4
Statistical Methods
In general, efficacy, safety, and baseline characteristics variables will be presented using descriptive 
statistics and graphs, as appropriate. Continuous endpoints will be summarized using descriptive 
statistics (e.g., mean, median, standard deviation, minimum and maximum values). Categorical 
endpoints will be presented in frequency tables with number and percentage of observations for each 
level.
95% confidence intervals (CIs) will be calculated whenever appropriate.
10.1.5
Subgroup Analysis
Subgroup analysis may be performed as determined and identified during the data review meeting. 
10.2
Sample Size Determination
The sample size of approximately 250 subjects is not based on a statistical calculation. The selected 
number of subjects is regarded as sufficient for an evaluation of the studied endpoints by using 
descriptive statistics.
10.3
Analysis
Since this is an open non-interventional study, available data may be analyzed prior to study 
completion.
  
 
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11
TRAINING / MONITORING / DATA MANAGEMENT / QUALITY ASSURANCE
11.1
Personnel Training
Investigators (i.e., physicians) and other responsible persons should be listed together with their 
function on the signature and delegation log. Study staff shall provide a curriculum vitae or 
equivalent, as appropriate.
It is the responsibility of the Investigator to ensure that all personnel involved in the study are fully 
informed of all relevant aspects of the study, including detailed knowledge of and documented 
training in all procedures to be followed.
11.2
Clinical Monitoring
The conduct of the clinical study will be closely monitored by representatives of the Sponsor to 
verify adherence to the clinical study protocol, ICH-GCP guidelines, national regulations, and
applicable SOPs.
The Investigator will allow the Contract Research Organization (CRO)/Sponsor’s representatives, 
to have direct access to all clinical study records, eCRFs, corresponding subject medical records, 
product(s) dispensing records, and any other documents considered source documentation.
Additionally, the CRO/Sponsor representative is to have access to the product storage area and 
clinical study facilities.
The Investigator also agrees to assist the representative if required.
11.3
Data Management
All data management procedures will be detailed in a Data Management Plan (DMP). 
11.4
Quality Assurance / Audit / Inspection
The clinical study is conducted under the sponsorship of the Sponsor in compliance with the 
applicable international and local regulatory requirements, applicable ICH guidelines, and SOPs for 
clinical study conduct and monitoring from the Sponsor and/or the CRO.
Audits of clinical study centers may be conducted by the Sponsor/CRO representatives, and 
inspection may be performed by Regulatory Authority (RA) inspectorates or Independent Ethics 
Committees (IECs) before, during, or after the clinical study.
The Investigator will allow and assist the CRO/Sponsor’s representatives, IECs and any regulatory 
agency to have direct access to all requested clinical study-related records.
For the audits performed by, or on behalf of, the Sponsor auditors, audit certificate(s) will be 
provided by Quality Assurance.
  
 
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11.5
Changes in Clinical Study Conduct / Amendments
11.5.1
Clinical Study Conduct
With the exception of eliminating an immediate hazard to a subject, the Investigator should not 
deviate from the clinical study protocol or implement any changes without written approval from 
the Sponsor and prior review and documented approval/favorable opinion from the IEC of a protocol 
amendment.
Changes that involve only logistical or administrative changes to the clinical study protocol are 
authorized. The Investigator should document and explain any deviation from the clinical study
protocol.
11.5.2
Amendments
The Sponsor may modify the clinical study protocol at any time for ethical, medical, or scientific 
reasons. Any amendments will be handled according to applicable local regulations.
The Sponsor does not have to notify non-substantial amendments to the competent authorities or the 
IEC. However, non-substantial amendments should be recorded and detailed in subsequent 
submissions e.g., in the subsequent notification of a substantial amendment.
  
 
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12
ETHICS AND GENERAL CLINICAL TRIAL CONDUCT CONSIDERATIONS
12.1
Independent Ethics Committee (IEC) 
This clinical study protocol and all amendments will be reviewed and approved by the appropriate 
IECs.
This CSP and all applicable amendments will be reviewed and approved by the appropriate IEC. It 
is the responsibility of the Investigator to obtain approval of the CSP/CSP amendment(s) from the 
IEC. The study shall not begin until the required favorable opinion from the IEC has been obtained. 
The Investigator shall file all correspondence with the IEC in the Investigator file and provide copies 
of IEC approvals to the Sponsor as required. Any additional requirements imposed by the IEC or 
RA shall be followed.
12.2
Ethical Conduct of the Clinical Study
This clinical study will be conducted in accordance with the protocol, the HELSINKI declaration 
(1964) and subsequent amendments, and the ICH GCP, and in compliance with applicable national 
regulatory requirements.
12.3
Subject Information and Consent
All subjects who participate in this clinical study are required to be fully informed about the clinical 
study in accordance with GCPs guidelines, federal regulations, and guidelines and in accordance 
with local requirements.
The ICF approved by an IEC, will be fully explained to the subject.
Prior to enrollment into the clinical study, the subject and the Investigator must sign and date the 
consent form(s). The Investigator is responsible for maintaining each subject’s consent form(s) in 
the Investigator’s site file and providing each subject with a copy of the signed and dated consent 
form(s).
12.4
Protection of Personal Data
The completion of the study involves the gathering and processing of Personal Data as specified in 
the Regulation (EU) 2016/679 on the protection of individuals with regard to the processing of 
personal data and on the free movement of such data. For the purposes of the study, Sponsor will be 
considered the Data Controller, and Investigator and Institution will both be considered Data 
Processors.
All processing of Personal Data must be carried out in accordance with national legislation 
concerning the protection of Personal Data. The Institution and Investigator are responsible for 
complying with all requirements pursuant to national legislation in the country in which the 
Institution and Investigator are located.
The Sponsor shall, to the extent feasible, protect study subject identifier information.
  
 
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The Institution and Investigator are jointly responsible for obtaining the appropriate informed 
consent of each subject for the processing of Personal Data required in order to complete the study. 
Such consent shall include the consent to the transfer of Personal Data to government authorities 
located in countries outside the China. 
The Institution and Investigator are jointly responsible for providing sufficient information to all 
subjects to enable them to give their informed consent not only to the participation in the study, but 
also to the processing of Personal Data. Such information includes information regarding the 
purposes of the processing, the length of time during which Personal Data will be stored, the right 
of access to stored Personal Data and the right to correction or purging of incorrect or obsolete 
Personal Data. A subject may also withdraw his or her consent at any time. A subject who withdraws 
his or her consent to the processing of Personal Data must be considered to have withdrawn from 
the study but the data collected until the consent was withdrawn may be used in the statistical 
analyses.
Authorized representatives from the Sponsor or a RA may visit the study center to perform 
audits/inspections, including source data verification, i.e., comparing data in the subjects’ medical 
records and the eCRF. Data and information shall be handled strictly confidential.
All collection, processing and analyses of protected health information, personal data or similar will 
be conducted in compliance with applicable local, national and international rules, regulations and 
guidelines.
12.5
Contractual Requirements
A contractual agreement will be signed between the CRO/Sponsor and each Investigator/Institution.
This document will contain supplementary information, including financial terms, confidentiality, 
the clinical study schedule, third party responsibility, and publication rights.
12.6
Data Collection and Archiving
12.6.1
Data Collection
The Investigator must maintain all required records for all subjects. Data for this clinical study will 
be recorded in the subject’s source documents and in the eCRFs provided by the Sponsor. All data 
should be recorded in the eCRFs completely and promptly.
12.6.2
Source Documentation
The eCRF is considered a data entry form and does not constitute the original (or source) medical 
records unless otherwise specified. Source documents are all documents used by the Investigator or 
hospital that relate to the subject’s medical history, verifying the existence of the subject, the 
inclusion and exclusion criteria, and all records covering the subject’s participation in the study. 
Source documents may include a subject’s medical records, hospital charts, clinic charts, the 
physician’s subject study files, as well as the results of diagnostic tests such as laboratory tests, 
electrocardiograms, etc.
  
 
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The Investigator must keep accurate separate records (other than the eCRFs) of all subject visits, 
being sure to include all pertinent clinical study-related information. A statement should be made 
indicating that the subjects have been included in this clinical study and have provided signed written 
Informed Consent. All AEs must be thoroughly documented.
Source documents shall be made available for inspection by the monitor at each monitoring visit, 
as well as during audits and/or inspections.
12.6.3
Archives
All pertinent data, samples, photographs, correspondence, and reports, the original or amended 
clinical study protocol, and all other material relating to the clinical study will be maintained 
securely in Sponsor/CRO/Investigator/Institution archives for the legally required duration for 
archiving.
The Investigator/Institution should maintain the essential clinical study documents as specified in 
Section 8 of ICH-GCP, and according to the applicable regulatory requirements.
The Investigator/Institution should take measures to prevent accidental or premature destruction of 
these documents.
If the Investigator retires, relocates, or withdraws from the responsibility of keeping the clinical 
study records for any other reasons, custody must be transferred to a person who will accept the 
responsibility. The Sponsor/CRO must be notified in writing of the name and address of the new 
custodian.
12.7
Insurance
A certificate attesting Third Party coverage of CRO/Sponsor will be provided upon request.
12.8
Publication Policy
The Institution/Investigator and the Sponsor’s obligations regarding intellectual property rights, 
confidentiality, and publications are described in detail in the Clinical Trial Agreement.
The aim is to submit the results of this study for publication in a public database (e.g., 
www.ClinicalTrials.gov) and to a medical journal for publication of the results. Everyone who is to 
be listed as an author of the results of this multicenter study shall have made a substantial, direct, 
intellectual contribution to the work. Authorship will be based on (1) substantial contributions to the 
conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; 
and (2) drafting the work or revising it critically for important intellectual content; and (3) final 
approval of the version to be published; and (4) agreement to be accountable for all aspects of the 
work in ensuring that questions related to the accuracy or integrity of any part of the work are 
appropriately investigated and resolved.a Conditions 1, 2, 3, and 4 must all be met in order to be 
                                                
a Defining the role of authors and contributors, compiled by the International Committee of Medical Journal Editors 
(ICMJE) (http://www.icmje.org).
  
 
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designated as author. Those who do not meet all four criteria will be acknowledged. Among the 
authors that fulfil the above mentioned criteria, one author will be appointed by the Sponsor to take 
primary responsibility for the overall work as primary author.
  
 
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13
LITERATURE REFERENCE LIST
1. Monheit GD, Pickett A. AbobotulinumtoxinA: A 25-Year History. Aesthet Surg J. 2017 May 
1;37(suppl_1):S4-S1.
2. Carruthers J, Carruthers A. The evolution of botulinum neurotoxin type A for cosmetic 
applications. J Cosmet Laser Ther. 2007 Sep;9(3):186-92.
3. Rzany B, Dill-Müller D, Grablowitz D, et al. Repeated botulinum toxin A injections for the 
treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. 
Dermatol Surg. 2007 Jan;33(1 Spec No.):S18-25.
4. Botulinum Toxin Type A for Injection Leaflet Dysport®. Berkshire, UK: Ipsen Biopharm Ltd: 
17 Jun 2020.
  
 
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Appendix 1
Subject Satisfaction Questionnaire
Subject #:
Visit #:
Date of questionnaire completion (DD/MM/YYYY):
Please tick the box corresponding to your preferred answer (only one box should be ticked by 
question unless otherwise specified).
Complete at Visit 1 ONLY
4. How satisfied have you been with the aesthetic outcome in the injected area after 
treatment?

Very satisfied

Satisfied

Dissatisfied

Very dissatisfied 
5. How satisfied were you with the comfort of the injection?

Very satisfied

Satisfied

Dissatisfied

Very dissatisfied 
  
 
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Complete at Visit 6 ONLY
17. What is your overall satisfaction after three treatment cycles with Dysport?

Very satisfied

Satisfied

Dissatisfied

Very dissatisfied 
  
 
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Appendix 2
Physician Satisfaction Questionnaire
Subject#:
Visit #:
Date of questionnaire completion (DD/MM/YYYY):
Please tick the box corresponding to your preferred answer (only one box should be ticked by 
question unless otherwise specified).
  
 
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Complete at Visits 6 ONLY
7. What is your overall satisfaction after three treatment cycles with Dysport?

Very satisfied

Satisfied

Dissatisfied

Very dissatisfied 
  
 
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Appendix 3
Subject Self-Assessment of GL Severity using the 4-point Categorical Scale
Subject#:
Visit #:
Date of completion (DD/MM/YYYY):
Subject Instructions: Using a mirror, evaluate your ‘glabellar lines’ (the lines between your 
eyebrows) while you are frowning. To produce a ‘max frown’ you are to raise your eyebrows, then 
bring them together as strongly as you can. You may repeat this until you are comfortable with 
frowning. Evaluate your lines at max frown according to these four categories shown below. 
These assessments will be repeated at each visit in the study center and we will ask that you make 
the max frown in exactly the same way on each occasion. Please place a mark (X) in the box that 
best describes how you think the lines between your eyebrows look when frowning today.
At max frown:
No wrinkles
(smooth skin)
Mild wrinkles
(fairly smooth skin)
Moderate wrinkles
(glabellar lines)
Severe wrinkles
(severe glabellar lines)
Please be advised that you will be using the same scale to rate the appearance of your glabellar 
lines at every visit.
Note: The subject should perform their self-assessment independently of the physician’s assessment.
Note: With guidance from the physician, subjects may also reference the 
 
 when completing their self-assessment. 
  
 
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15
SIGNED AGREEMENT OF THE CLINCAL STUDY PROTOCOL
CTN:
05PF2009
CSP Title:
A Prospective, Non-interventional Study to Collect Subject and 
Physician Satisfaction During Long Term Treatment of Glabellar 
Lines with Dysport® in Subjects of Chinese Origin in Real Clinical 
Practice
I, the undersigned, have read and understand the CSP specified above, and agree on the contents. 
The CSP, the CTA, and the additional information given in the prescribing information will serve 
as a basis for cooperation in this study.
Investigator
Printed name 
Signature
Date
Study center
  
 
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PPD