A Multicenter, Open-Label, Prospective Study of Cannula Injection of Restylane Lyft With Lidocaine for Cheek Augmentation and the Correction of Age Related Midface Contour Deficiencies
Phase: NA
Conditions: Cheek Augmentation, Midface Contour Deficiencies
Sponsor: Galderma R&D

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A  Multicenter,  Open-Label,  Prospective  Study  of  Cannula  Injection 
of Restylane® Lyft with Lidocaine for Cheek Augmentation and the 
Correction of Age Related Midface Contour Deficiencies
Study products:
Restylane® Lyft with Lidocaine
Clinical trial number (CTN):
43USC1633 
Sponsor:
Q-Med AB, a Galderma affiliate
Confidentiality Statement
This study protocol contains confidential information belonging to Q-Med AB, a Galderma 
affiliate. Except as may be otherwise agreed to in writing, by accepting or reviewing these 
materials, you agree to hold such information in confidence and neither disclose it to any 
third parties (except where required by applicable law) nor use it for any other purpose than 
in relation to the clinical study described herein. 
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Investigators and Study Administrative Structure
Sponsor:
Q-Med AB, a Galderma affiliate
Medical expert:
Clinical Project Manager:
Study Statistician:
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 clinical investigational plan (CIP) amendment.
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Sponsor Signatures
The CIP is electronically signed in the document management system within the Q-Med AB 
quality management system by the representatives listed below.
Medical Expert, Q-Med AB, 
Head of Global A&C Clinical Development, Q-Med AB
 
Clinical Project Manager, Galderma R&D, LLC
Statistician, Q-Med AB
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Signed Agreement of the Clinical Study Protocol
CTN:
43USC1633
Title of the CIP:
A  Multicenter,  Open-Label,  Prospective  Study  of  Cannula  
Injection of Restylane® Lyft with Lidocaine for Cheek Augmentation 
and the Correction of Age Related Midface Contour Deficiencies
I, the undersigned, have read and understand the CIP specified above, and agree on the 
contents. The CIP, the clinical trial agreement (CTA) and the additional information given in 
the IFU and Report of Prior Investigations (ROPI) will serve as a basis for co-operation in 
this study.
Principal Investigator
Printed name 
Signature
Date
Study site name and address
____________
Study site number
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may have facial cosmetic procedures outside the area of 
assessment (e.g., neurotoxin injections above the orbital rim, 
etc.) either before or
contemporaneously with cheek
augmentation and correction of age related midface contour 
deficiency.
5. If the subject is a female of childbearing potential, she
agrees to use an acceptable form of effective birth control 
for the duration of the study and is willing to take a urine
pregnancy test at the screening/enrollment visit, prior to 
treatment/injection, and at the exit visit.
Acceptable forms of effective birth control include:

Barrier methods of contraception: Condom or
Occlusive cap (diaphragm or cervical caps) with 
spermicidal foam/gel/film/cream/suppository;

Bilateral tubal ligation;

Combined oral contraceptives (estrogens and 
progesterone), 
implanted 
or
injectable
contraceptives on a stable dose for at least 28 
days prior to Day 1;

Hormonal intra uterine device (IUD) inserted at 
least 28 days prior to Day 1;

Vasectomised partner (in monogamous relationship) 
for at least 3 months prior to screening;

Strict abstinence (at least one month prior to baseline
and agrees to continue for the duration of the study)
6. Passed functionality and sensory tests. 
7. Negative urinary pregnancy test for women of childbearing 
potential at the screening and injection visit.
Exclusion criteria:
1. Known/previous allergy or hypersensitivity to any injectable 
hyaluronic acid gel or to gram positive bacterial proteins. 
2. History of allergy or hypersensitivity to lidocaine or other 
amide-type anaesthetics, or topical anaesthetics or nerve 
blocking agents (if such products are intended to be used for 
that subject).
3. History of severe or multiple allergies e.g., manifested by 
anaphylaxis.
4. History of or active collagen diseases or autoimmune diseases 
such as multiple sclerosis, systemic lupus erythematosus, 
rheumatoid arthritis, skin or systemic sclerosis.
5. History of radiation of or presence of cancerous or 
precancerous lesions (e.g., actinic keratosis) or tattoo in the 
treatment area.
6. History of bleeding disorders or use of concomitant 
medication that has the potential to prolong bleeding times 
such as anticoagulants or inhibitors of platelet aggregation 
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(e.g. aspirin or other non-steroidal anti-inflammatory drugs 
[NSAIDs}, omega 3 or vitamin E), within 14 days prior to 
injection.  Omega 3 and Vitamin E are acceptable only as part 
of a standard multivitamin formulation.
7. Treatment with chemotherapy, immunosuppressive agents, 
immunomodulatory therapy (e.g., monoclonal antibodies), 
systemic corticosteroids (inhaled corticosteroids are allowed) 
within 3 months before study treatment.
8. Treatment with systemic retinoids within 6 months, topical 
(facial) prescription retinoids or corticosteroids below the 
level of the lower orbital rim within 1 month before study 
treatment.
9. Have undergone prior surgery to midface including facial 
plastic surgery, lifting threads, tissue grafting, or tissue 
augmentation with permanent implants, silicone, fat, or other 
permanent or semi-permanent dermal fillers, or is planning to 
undergo any of these procedures affecting the treatment area, 
at any time during the study. 
10. History of other facial treatment/procedure in the previous 
6months below the level of the lower orbital rim that, in the 
Treating Investigator’s opinion, would interfere with the 
study injections and/or study assessments or exposes the 
subject to undue risk by study participation, e.g., dental work, 
dental root or sinus surgery, or resurfacing (laser, 
photomodulation, intense pulsed light [IPL], radio frequency, 
dermabrasion, chemical peel or other ablative/non-ablative 
procedures), or mesotherapy, or neurotoxin injections, or is 
planning to undergo any of these procedures affecting the 
treatment area, at any time during the study. 
11. Previous use of any HA based or collagen based 
biodegradable facial tissue augmentation therapy below the 
level of the lower orbital rim within 12 months prior to any 
study injections.  
12. Have received any other therapy, which, in the opinion of the 
investigator, could interfere with safety or efficacy 
evaluations.
13. History of or the presence of any disease, in the area to be 
treated which may result in changes in facial contour or 
edema of the face during the course of the study, such as 
inflammation, active or chronic infection (e.g. in mouth, 
dentals, sinuses etc.), facial psoriasis eczema, acne, rosacea, 
perioral dermatitis, herpes zoster, acanthosis, etc.
14. Have a history of prior significant trauma resulting in 
scarring, fibrosis or deformation in the area to be treated.
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(inclusive). Cannula length depends on the injection technique and
the anatomic location being treated; in general, cannula length
ranging from 1 - 2 inches long is recommended. The Treating 
Investigator should use the amount of dermal filler necessary to
achieve an optimal augmentation for each subject, however, it is
recommended that a volume not to exceed 6 mL of filler be injected. 
Optimal augmentation is defined as the best possible aesthetic result 
that can be obtained for an individual study subject, as agreed upon
by the Treating Investigator and subject.
The injection technique, including use of anesthesia, is left to the
discretion of the Treating Investigator.
Reference therapy
N/A
Schedule of Events

Screening (Day -14 to Day 1).

Treatment visit (Baseline; Day 1). Screening visit and 
baseline visit can be combined if no washout is needed

Follow-up (telephone contact) 72 hrs

Follow-up after treatment at 2, 4, 8 and 16 weeks
For subjects receiving re-treatment at the Week 16 visit:

Follow-up (telephone contact) 72 hrs

Follow-up after treatment at 2 weeks
Efficacy Assessment:
Safety Assessment:
1. Adverse Event reporting: AEs will be obtained from signs 
and symptoms reported by the subject or detected during each 
examination.
2. A subject diary will be dispensed to all subjects for daily 
completion over the first 2 weeks after treatment to record the 
presence of adverse reactions. Information from the diary will 
be presented separately from AEs.
3. Safety evaluations according to pre-defined methods, at 
baseline and at each physical follow-up visit.
Statistical Methods: 
Sample size
Sixty (60) subjects will be enrolled with the goal of 50 subjects 
completing the study. The sample size has been established based on 
the probability of detecting an AE given the true population rate of 
5%. This 5% criterion has been selected based on this value 
representing the point-estimate cut-off AE rate for inclusion in 
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Abbreviations and Definitions of Terms
AE
Adverse event 
BDDE
1,4-butanediol diglycidyl ether
CE
“Conformité  Européenne” – the quality and branding mark for products 
made or sold within the European Union.
CFR
Code of Federal Regulations
CIP
Clinical Investigational Plan
Childbearing 
Potential
A female (including pre-menopausal subjects) capable of becoming 
pregnant. This includes women on oral, injectable or mechanical 
contraception; women who are single, women whose husbands have been 
vasectomised or whose husbands have received or utilizing mechanical 
contraceptive devices.
CRF
Case report form
CTA
Clinical trial agreement
CTN
Clinical trial number
CV
Curriculum vitae
Device 
deficiency
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance (includes malfunctions, use 
errors, and inadequate labelling)
DMC
Data monitoring committee
DMP
Data management plan
eCRF
Electronic case report form
ET
Early termination
FDA
United States Food and Drug Administration
First subject 
in
First subject screened, i.e. who signs the informed consent form
First subject 
out
First subject who completed their last study visit
G
Gauge
GCP
Good clinical practice
HA
Hyaluronic acid
HIPAA
Health Insurance Portability and Accountability Act
ICH
International Conference on Harmonisation
IFU
Instructions for use
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Institution
Any public or private entity or agency or medical or dental facility where a 
clinical study is conducted.
Investigator
The Principal Investigator (PI) or other qualified person, i.e. sub-
investigator, designated and supervised by the PI at a study site to perform 
critical study-related procedures or to make important study-related 
decisions as specified on the signature and delegation log
Investigator 
file
Essential documents relating to a clinical study as defined in applicable 
GCP guidance document and maintained by the Investigator.
IRB
Institutional review board
ISO
International Organization for Standardization
ITT
Intention-to-treat
Last subject 
in
Last subject who entered the study
Last subject 
out
Last subject who completed their last study visit
MedDRA
Medical dictionary for regulatory activities
NSAID
Non-steroidal anti-inflammatory drugs
PI
Principal Investigator; qualified person responsible for conducting the study 
at a study site
PP
Per protocol
PT
Preferred term
QA
Quality assurance
RA
Regulatory authority
ROPI
Report of Prior Investigations, i.e. compilation of the current clinical and 
non-clinical information on the investigational product, relevant to the 
clinical study
SAE
Serious adverse event
SAP
Statistical Analysis Plan
SDV
Source data verification
SOC
System Organ Class
Sponsor file
Essential documents relating to a clinical study as defined in applicable 
GCP guidance document and maintained by the Sponsor.
Study files
The Investigator file and the Sponsor file
Study 
products
The investigational product and the reference product under study
Study site
Institution or site where the study is carried out
TC
Telephone Call
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Tx
Treatment
WHO
World Health Organization
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Table of Contents
SUMMARY OF CHANGES IN CLINICAL STUDY PROTOCOL FROM VERSION 1.0 TO 
VERSION 2.0
2
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE
3
SIGNED AGREEMENT OF THE CLINICAL STUDY PROTOCOL
5
SYNOPSIS
6
ABBREVIATIONS AND DEFINITIONS OF TERMS
14
LIST OF TABLES
20
LIST OF APPENDICES
20
1.
ETHICAL CONSIDERATIONS
21
1.1
Statement of ethical compliance
21
1.2
Application to independent ethics committee and/or regulatory authorities
21
2.
BACKGROUND INFORMATION
21
2.1
Indication and population description
21
2.2
Investigational product description
21
2.3
Reference product description
22
2.4
Previous experience
22
2.4.1
Non-clinical documentation
22
2.4.2
Clinical documentation
22
2.5
Study rationale
22
2.6
Justification for the design of the study
22
2.7
Risks and benefits
23
3.
OBJECTIVE(S) AND ENDPOINT(S)
23
3.1
Objectives and endpoints
23
3.1.1
Primary safety objective and endpoint
23
3.1.2
Secondary objectives and endpoints
24
4.
DESIGN OF THE STUDY
24
4.1
General outline
24
4.2
Number of subjects
24
4.3
Duration of subject participation
24
4.4
Randomisation and blinding
25
4.4.1
Randomisation
25
4.4.2
Blinding
25
4.4.3
Emergency unblinding
25
4.5
Medical history
25
4.6
Concomitant medications, treatments, and procedures
25
4.7
Schedule of events
27
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4.8
Visits
28
 
5.
SUBJECTS
32
5.1
Subject information and informed consent
32
5.2
Inclusion criteria
33
5.3
Exclusion criteria
33
5.4
Screening and subject numbers
35
5.5
Withdrawal of subjects
35
6.
STUDY PRODUCTS
36
6.1
Investigational product
36
6.2
Additional products and material
36
6.3
Packaging, labelling, and storage
37
6.3.1
Investigational product
37
6.3.2
Reference product
37
6.4
Product accountability
37
6.5
Treatment
38
6.5.1
Treatment Procedure
38
6.5.2
Recommended Injection Technique
38
6.5.3
Recommended Post- Treatment
39
6.5.4
Treatment regimen (dose and interval)
39
6.5.5
Post-trial provisions
40
6.5.6
Treatment compliance
40
7.
EFFICACY ASSESSMENTS
40
7.1
General information
40
7.2
Photography
40
8.
SAFETY ASSESSMENTS
41
8.1
Assessment of AEs by direct question to subject and evaluation of subject
41
8.2
Pre-defined, expected, post-treatment events
42
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8.3
Other Safety Assessments
42
8.4
Laboratory assessments
43
8.5
Adverse events
43
8.5.1
Definition of an adverse event
43
8.5.2
Definition of a serious adverse event
44
8.5.3
Recording instructions
44
8.5.4
Reporting of adverse events
45
8.5.5
Reporting of serious adverse events
45
8.5.6
Follow-up of ongoing related events after termination of the study and events with onset after termination of 
study (subject last visit)
47
8.5.7
Pregnancy
47
8.5.8
Anticipated adverse events
47
8.6
Device deficiencies
47
8.6.1
Definition of a device deficiency
47
8.6.2
Recording instructions
47
8.6.3
Reporting of device deficiencies
48
9.
DATA HANDLING AND MANAGEMENT
48
9.1
Data management
48
9.2
Electronic case report forms
49
9.2.1
Data entry
49
9.2.2
The query process
49
9.2.3
User identification
50
9.2.4
Audit trail
50
9.3
Source documents
50
9.4
Record keeping and access to source data
50
9.5
Document and data retention
50
10.
STATISTICAL METHODS
51
10.1
General
51
10.2
Analysis populations
51
10.3
Demographics, baseline assessments, and subject characteristics
51
10.4
Efficacy analysis
51
10.5
Safety analysis
52
10.6
Handling of missing data
52
10.7
Interim analysis
52
10.8
Data monitoring committee
52
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10.9
Withdrawals and deviations
52
10.10
Sample size
52
11.
PROTECTION OF PERSONAL DATA
53
12.
QUALITY CONTROL AND QUALITY ASSURANCE
53
12.1
Quality control
53
12.2
Quality assurance
54
12.3
Changes to the clinical study protocol
54
13.
FINANCING, INDEMNIFICATION, AND INSURANCE
54
14.
PUBLICATION POLICY
54
15.
SUSPENSION OR PREMATURE TERMINATION
55
16.
REFERENCES
56
List of Tables
List of Appendices
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
 
 
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3. History of severe or multiple allergies e.g., manifested by anaphylaxis.
4. History of or active collagen diseases or autoimmune diseases such as multiple 
sclerosis, systemic lupus erythematosus, rheumatoid arthritis, skin or systemic 
sclerosis.
5. History of radiation of or presence of cancerous or precancerous lesions (e.g., actinic 
keratosis) or tattoo in the treatment area.
6. History of bleeding disorders or use of concomitant medication that has the potential 
to prolong bleeding times such as anticoagulants or inhibitors of platelet aggregation 
(e.g. aspirin or other non-steroidal anti-inflammatory drugs [NSAIDs}, omega 3 or 
vitamin E), within 14 days prior to injection.  Omega 3 and Vitamin E are acceptable 
only as part of a standard multivitamin formulation.
7. Treatment with chemotherapy, immunosuppressive agents, immunomodulatory 
therapy 
(e.g., 
monoclonal 
antibodies), 
systemic 
corticosteroids 
(inhaled 
corticosteroids are allowed) within 3 months before study treatment.
8. Treatment with systemic retinoids within 6 months, topical (facial) prescription 
retinoids or corticosteroids below the level of the lower orbital rim within 1 month 
before study treatment.
9. Have undergone prior surgery to midface including facial plastic surgery, lifting 
threads, tissue grafting, or tissue augmentation with permanent implants, silicone, fat, 
or other permanent or semi-permanent dermal fillers, or is planning to undergo any of 
these procedures affecting the treatment area, at any time during the study. 
10. History of other facial treatment/procedure in the previous 6months below the level of 
the lower orbital rim that, in the Treating Investigator’s opinion, would interfere with 
the study injections and/or study assessments or exposes the subject to undue risk by 
study participation, e.g., dental work, dental root or sinus surgery, or resurfacing 
(laser, photomodulation, intense pulsed light [IPL], radio frequency, dermabrasion, 
chemical peel or other ablative/non-ablative procedures), or mesotherapy, or 
neurotoxin injections, or is planning to undergo any of these procedures affecting the 
treatment area, at any time during the study. 
11. Previous use of any HA based or collagen based biodegradable facial tissue 
augmentation therapy below the level of the lower orbital rim within 12 months prior 
to any study injections.  
12. Have received any other therapy, which, in the opinion of the investigator, could 
interfere with safety or efficacy evaluations.
13. History of or the presence of any disease, in the area to be treated which may result in 
changes in facial contour or edema of the face during the course of the study, such as 
inflammation, active or chronic infection (e.g. in mouth, dentals, sinuses etc.), facial 
psoriasis eczema, acne, rosacea, perioral dermatitis, herpes zoster, acanthosis, etc.
14. Have a history of prior significant trauma resulting in scarring, fibrosis or deformation 
in the area to be treated.
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8.4
Laboratory assessments
Pregnancy Test
For all women of childbearing potential, a urine pregnancy test will be performed at 
screening and baseline (prior to treatment) and at study exit. The test result will be 
documented in the source documents and eCRF.
8.5
Adverse events
8.5.1
Definition of an adverse event
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons1, 
whether or not related to the study product. 
This definition includes:
a) events related to the investigational product or the reference product
b) events related to the procedures involved
                                                
1 For users or other persons, this definition is restricted to events related to the investigational product.
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8.5.2
Definition of a serious adverse event
A serious adverse event (SAE) is an AE that:
a) led to death,
b) led to serious deterioration in the health of the subject, that either resulted in
1. a life-threatening2 illness or injury, or
2. a permanent impairment of a body structure or body function, or
3. in-patient or prolonged hospitalisation3, or
4. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function,
c) led to foetal distress, foetal death, or a congenital abnormality or birth defect
An AE does not need to be recorded as a SAE if it only represents a relapse or an expected 
change or progression of the condition that was the cause of the treatment, without the 
development of new symptoms and signs.
In cases of doubt, whether an AE fulfils a serious criterion or not, there should be a 
predisposition to report as a SAE rather than not report as such (see section 8.5.5).
8.5.3
Recording instructions
Each subject with an AE occurring after signing of the informed consent form through study 
exit should be fully recorded in the source document for further transcription to the eCRF.  
Each subject should be questioned about AEs at each study visit following the screening visit.
The question asked should be: “Since your last clinical visit have you had any health 
problems?” Information on AEs can also be obtained from signs and symptoms detected 
during each examination.  
When an AE is related to a device deficiency including technical device malfunction, the AE 
should be recorded in the AE eCRF and technical complaint should be reported separately on 
the study complaint form.  
Investigators, or other study site personnel, shall record all AEs in the eCRF, including:
a) Event term (recorded in standard medical terminology and avoiding abbreviations)
b) Description of event and affected area 
c) Start date (first day with symptoms)
d) Stop date (last day with symptoms)
e) Intensity (mild, moderate, or severe according to definition in Section 8.5.3.1)
f)
Seriousness (serious or not serious, according to definition in Section 8.5.3.2)
                                                
2 The term “life-threatening” in the definition of “serious” refers to an event in which the patient 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. (Source: ICH-E2A clinical safety data management: definitions and standards for expedited 
reporting).
3 Planned hospitalisation for a pre-existing condition, or a procedure required by the CSP, without serious 
deterioration in health, is not considered a SAE. (Source: ISO14155:2011).
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g) Causal relationship to study product or study product injection procedure (yes or no)
h) Action taken (none, medication treatment, non-medication treatment, or other 
procedures/tests, subject withdrawn)
i)
Outcome of the AE (ongoing, recovered, recovered with sequelae, death, chronic/ 
stable, not recovered at the end of the study)
The pre-defined, expected post-treatment events shall be assessed separately. These events 
shall be collected by subjects in a diary used daily for 14 days after the treatment.
8.5.3.1
Intensity
Intensity will be recorded for each reported AE. The following definitions of intensity are to 
be used:
Mild:
Awareness of symptoms or signs, but easily tolerated (acceptable)
Moderate:
Enough discomfort to interfere with usual activity (disturbing)
Severe:
Incapacity to work or to do usual activity (unacceptable)
If the intensity changes within one day, the maximum intensity of the AE during that day 
shall be recorded.
8.5.3.2
Causal relationship and seriousness
Each AE, serious as well as non-serious, shall be assessed by the Investigator for causal 
relationship with the study product and its use (the injection procedure) and for seriousness
(Yes or No) of the event. 
A two-point scale (Yes or No response) shall be used for the causality assessments. The 
Investigators shall be asked to indicate a response to each of the following questions in the 
eCRF:

“Do you consider that there is a reasonable possibility that the event may have been 
caused by the study product?”, and 

“Do you consider that there is a reasonable possibility that the event may have been 
caused by the device injection procedure?”
If any of these questions is answered Yes, the AE is considered related.
Each AE will also be assessed for causal relationship and seriousness by the Sponsor, in order 
to fulfil regulatory requirements. 
8.5.4
Reporting of adverse events 
Adverse event reporting on each subject shall start at screening visit after the signature of the 
ICF. The reporting shall continue during each follow-up visit (including telephone contacts
and extra visits between planned visits) until the last scheduled visit in the study.
All AEs, non-serious as well as serious, are to be reported as an AE in the eCRF.
8.5.5
Reporting of serious adverse events
The Investigator shall report any SAE to the Sponsor immediately but not later than 24 
hours of awareness of the event. This initial report can be made via e-mail.
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In case of difficulty to obtain all the required information within 24 hours, an initial report 
can be submitted, with the following information as a minimum, irrespective of whether 
some of it is regarded as preliminary:

CTN: 43USC1633

Subject identification (age, gender, subject number)

Adverse event description

Date when AE occurred

Date when AE became serious

Name of Investigator and original reporter (if other than the Investigator)

Name of investigational device: Restylane® Lyft with Lidocaine

Treatment specification
Follow-up information and data missing in the initial SAE reporting shall be gathered as soon 
as possible and reported immediately but not later than 24 hours of awareness of the new 
data.  Complete and adequate information on each SAE is required.  All attempts to obtain 
this information, including dates for follow-up activities, must be documented by the 
Investigator or designated study staff.
Supporting documentation to be provided with the SAE report:

Concomitant medication form

Concomitant procedure/treatment form

AE form

Medical history form

Any other relevant supporting documentation (e.g. hospital notes, death certificate, 
autopsy reports etc.)
___________________________________________________________________________
E-mail for reporting:
___________________________________________________________________________
The SAE form must be signed and dated by the Investigator.  If the initial 24-hour SAE 
report does not contain full information or if it is made without using the SAE form the fully 
completed and signed SAE form shall be e-mailed to the Sponsor. A copy of the fully 
completed SAE form shall be kept at the site.
In addition, the Investigator shall report SAEs to the responsible IRB without undue delay, if 
applicable according to national regulations.  The Investigator is responsible for checking 
what reporting procedures are applicable for his/her IRB regarding SAEs and final report of 
the outcome of the study and to comply with such reporting procedures during the study 
period.
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8.5.6
Follow-up of ongoing related events after termination of the study and events with 
onset after termination of study (subject last visit) 
All serious as well as non-serious AEs with a causal relationship to the study product or 
treatment procedure and ongoing at study end, shall be followed up after the subject's 
participation in the study is over.  Such events shall be followed-up after the last study visit 
until resolved, or assessed as chronic or stable.  All AEs assessed as related to the study 
product or treatment procedure, serious as well as non-serious, with onset after the study 
termination (last subject study visit), and that the Investigator becomes aware of, should be 
reported to Sponsor in accordance with the post-marketing procedure as agreed upon with the 
corporate device vigilance group and the safety management plan.
8.5.7
Pregnancy
Pregnancy itself is not regarded as an AE.
If there is a pregnancy after the subject has been treated, the subject must continue to be 
followed within the study and the outcome of pregnancy must be reported even if the delivery 
occurs after study completion.
A pregnancy confirmed during the study period after treatment must be reported by the 
Investigator on a pregnancy report form immediately upon acknowledgement and submitted
to the Sponsor according to contact details specified in section 8.5.5. The report can be 
prospective or retrospective. Follow-up shall be conducted to obtain outcome information on 
all prospective reports. 
Cases that led to foetal distress, foetal death or a congenital abnormality or birth defect are to 
be regarded as SAEs and shall be reported on the exposure in utero report form to the 
Sponsor immediately but no later than 24 hours after the Investigators awareness. These 
events shall be handled as SAEs during data processing. Other complications during the 
pregnancy that are related to the pregnant woman and fulfils any serious criteria, such as pre-
eclampsia requiring hospitalisation, shall be reported and handled as SAEs. Elective 
abortions without complications shall not be reported as AEs.
8.5.8
Anticipated adverse events
Information regarding anticipated AEs is included in the Instructions for Use.
8.6
Device deficiencies
8.6.1
Definition of a device deficiency
A device deficiency is defined as an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety4, or performance.
Note: Device deficiencies include malfunctions, use errors, and inadequate labelling.
8.6.2
Recording instructions
When a device deficiency is discovered, Part A of the clinical study complaint form shall be 
completed by the Investigator or qualified designee. The type of complaint shall be described 
                                                
4 Inadequacy of device safety refers to properties of the device which could have or have led to an AE.
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and injury to the subject or user or unintended exposure to study product shall be reported as 
applicable. If an injury has occurred, an AE or an SAE form shall be completed as applicable 
(refer to section 8.5.5). If no SAE was experienced as a result of the device deficiency the 
Investigator shall assess whether or not the device deficiency could have led to an SAE if:

Suitable action had not been taken,

Intervention had not been made or,

Circumstances had been less fortunate
In Part B of the clinical study complaint form the Sponsor will make the same assessment. 
8.6.3
Reporting of device deficiencies
The Investigator shall send the completed clinical study complaint form to the Sponsor using
the contact details specified in section 8.5.5. A device deficiency that led to a SAE and any 
device deficiency that could have led to a SAE shall be reported within 24 hours after the 
Investigator’s awareness in accordance to section 8.5.5
In order to fulfil regulatory reporting requirements, all deficiencies with the study product 
must be assessed by both the Investigator and the Sponsor to determine if it could have led to 
a SAE.
If a SAE has resulted from a device deficiency or if either the Investigator or the Sponsor 
assesses that the device deficiency could have led to a SAE the Sponsor is responsible for 
reporting the device deficiency to RA and the PI is responsible for reporting it to the IEC.
The deficient study product shall be kept by the study site until the QA complaints group has 
confirmed whether the product shall be returned to Sponsor for further study or if it can be 
destroyed at the study site.
9. Data Handling and Management 
9.1
Data management
Data management based on GCP refers to the activities defined to achieve safe routines to 
enter clinical data information into a database, efficiently and avoiding errors. The data 
management routine includes procedures for handling eCRFs, database set-up and 
management, data entry and verification, data validation, and documentation of the 
performed activities including information of discrepancies in the process. The data 
management process will be described in detail in the data management plan (DMP).
The database, the data entry screens and program will be designed in accordance with the CIP
and the eCRF. Data validation will be performed by computerised logical checks and manual 
review. Drugs and events will be coded in accordance with World Health Organization 
(WHO) Drug and medical dictionary for regulatory activities (MedDRA) dictionaries as 
specified in the DMP. SAEs in the clinical database will be reconciled against the data in the 
safety database.
When all efforts have been made to ensure that the data recorded in the eCRFs and entered in 
the database is as correct and complete as possible, the clinical database will be locked. Study
data will be transferred to SAS datasets which thereafter will be write-protected. Statistical
analyses will be generated in SAS using data from the locked datasets.
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9.2
Electronic case report forms
A 21 Code of Federal Regulations (CFR) Part 11-compliant electronic data capture 
application will be used to collect, modify, maintain, archive, retrieve, and transmit study 
data.  An eCRF is required and shall be completed electronically for each screen failure as 
well as enrolled subjects. 
The eCRF includes password protection and internal quality checks, such as automatic range 
checks, to identify data that appear inconsistent, incomplete, or inaccurate.  Study data shall 
be entered directly from the source documents, which are to be defined at each site before 
inclusion of the first subject.
Authorized study site personnel designated by the Investigator shall complete data collection. 
Appropriate training and security measures shall be completed with all authorized 
investigation site personnel prior to the study being initiated and any data being entered into 
the system for any subject.
The study data is the sole property of the Sponsor and shall not be made available in any form
to third parties, except for authorized representatives of appropriate RA, without written 
permission from the Sponsor.  At the end of the study, electronic data are kept at the Sponsor 
and a copy (provided by the vendor) at the study site as part of the Investigator file.
Any delegation of collection of data shall be specified in a signature and delegation log.
9.2.1
Data entry
All data shall be entered in English. The eCRFs should always reflect the latest observations 
on the subjects participating in the study. Therefore, the eCRFs shall be completed as soon as 
possible during or after the subject’s visit. The subject’s identity must always remain 
confidential, i.e. the name and address of the subjects must not be registered in the eCRFs or 
in the database. The Investigator must verify that all data entries in the eCRFs are accurate 
and correct. If some assessments are not done, or if certain information is not available, not 
applicable or unknown, the Investigator shall indicate this in the eCRF. The Investigator shall
electronically sign off the study data. By signing, the Investigator takes responsibility for the 
accuracy, completeness, and legibility of the data reported to the Sponsor in the eCRF.
9.2.2
The query process
The monitor shall review the eCRFs and evaluate them for completeness and consistency. 
Each eCRF shall be compared with the respective source documents to ensure that there are 
no discrepancies between critical data. All entries, corrections, and alterations shall be made 
by the PI or his/her authorised designee. The monitor cannot enter data in the eCRFs. Once 
study data have been submitted to the central server via the eCRF, corrections to the data 
fields will be audit trailed, meaning that the reason for change, the name of the person who 
made the change, together with time and date will be logged. Roles and rights of the site 
personnel responsible for entering study data into the eCRF shall be determined in advance. 
If discrepant data is detected during review of the data, either by the Sponsor or its 
representatives, the responsible data manager or monitor shall raise a query in the electronic 
data capture application. The query shall state the question or data to be changed and shall be 
resolved in the system by the PI or his/her authorised designee. The appropriate study site 
personnel shall answer the queries in the eCRF. This will be audit trailed by the electronic 
data capture application meaning that the name of study site personnel, time, and date is 
logged.
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9.2.3
User identification
Electronic CRF records will be automatically appended with the identification of the creator, 
by means of their unique User ID. Specified records shall be electronically signed by the 
Investigator to document his/her review of the data and acknowledgement that the data are 
accurate. This will be facilitated by means of the Investigator’s unique User ID and 
password; date and time stamps will be added automatically at time of electronic signature. If 
an entry in an eCRF requires change, the correction shall be made in accordance with the 
relevant software procedures. 
9.2.4
Audit trail
All changes will be fully recorded in a protected audit trail and a reason for the change shall 
be stated. Once all data have been entered, verified, and validated, the database will be 
locked.
9.3
Source documents
Source documents are all documents used by the Investigator or hospital that relate to the 
subject’s medical history, that verifies the existence of the subject, the inclusion and 
exclusion criteria, and all records covering the subject’s participation in the study.  They 
include laboratory notes, memoranda, material dispensing records, subject files, etc.
The Investigator is responsible for maintaining source documents.  These shall be made 
available for inspection by the monitor at each monitoring visit.  The Investigator must 
submit a completed eCRF for each subject for whom signed informed consent has been 
collected.  All supportive documentation submitted with the eCRF, such as laboratory or 
hospital records, shall be clearly identified with the CTN and subject number. Any personal 
information, including name, shall be removed or rendered illegible to preserve individual 
confidentiality.
9.4
Record keeping and access to source data
The Investigator/Institution shall permit study-related monitoring, audits, IRB review, and 
RA inspections and shall provide direct access to the source data/medical record including 
the identity of all participating subjects (sufficient information to link records, i.e. eCRF, 
medical records, original signed informed consent forms and detailed records of study 
product accountability).  The records shall be retained by the Investigator as required by local 
legislation and international guidelines.  Any transfer of responsibility for storage of the 
records shall be documented and the Sponsor shall be informed in writing.
The Sponsor shall verify that each subject has consented in writing to direct access to the 
original medical record/source data (by the use of written subject information and signed 
informed consent).  The data recorded in the eCRFs will be checked for consistency with the 
source documents/medical record by the monitor during monitoring (source data verification; 
SDV).  In order to be able to perform SDV, information about each subject’s participation in 
the study has to be detailed in the medical record. 
9.5
Document and data retention
All records pertaining to the conduct of the study, including signed eCRFs, informed consent 
forms, study product accountability records, source documents, and other study 
documentation must be retained for as long as is specified in the CTA.  Measures shall be 
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12.2 Quality assurance
The study site may be subject to quality assurance audit by the Sponsor as well as inspection 
by appropriate RA.  It is important that the Investigator and other relevant study site 
personnel are available during the monitoring visits, possible audits, and inspections, and that 
sufficient time is devoted to the monitoring process.
Each participating member of the study site team shall provide a curriculum vitae (CV) or 
equivalent that demonstrates their qualifications to conduct the study.  
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 
training in all procedures to be followed.  All Investigators and other responsible persons 
shall be listed together with their function in the study on a signature and delegation log.
12.3 Changes to the clinical study protocol
The Investigator and other site personnel involved in the study must not implement any 
deviation from or changes to the CIP without agreement with the Sponsor and prior review 
and documented approval from the IRB, except where necessary to eliminate an immediate 
hazard to the subjects. All changes to the final CIP must be documented in a written protocol 
amendment.  However, administrative changes are to be documented in the Sponsor file 
without requiring a protocol amendment.  The Sponsor will assess if the changes require 
prior FDA approval, and inform the Investigator when such approval has been received.
13. Financing, Indemnification, and Insurance
The CTA outlines the compensation and payment terms of the study.  The CTA must be 
signed before the first subject is screened in the study.  If there are differences between the 
CTA and the CIP regarding certain rights and obligations, the CTA is the prevailing
document.
The Sponsor’s obligations in this clinical study are covered by Galderma’s global general 
liability program.
An
insurance
certificate will
be
provided
upon
request.  The
Institution/Investigator is obligated to maintain insurance coverage for their obligations in
the clinical study according to the CTA.
14. Publication Policy
The Investigator’s, Institution’s, and Sponsor’s obligations regarding intellectual property 
rights, confidentiality, and publications are described in detail in the CTA.
This study will be displayed on clinicaltrials.gov in accordance with local regulations.  The
aim is to submit the results of this study for publication.  Everyone who is to be listed as an 
author of the publication 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 
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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 resolved5.  Conditions 1, 2, 3, and 4 must
all be met in order to be 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 Q-Med AB to take primary responsibility for the overall work as 
primary author.
15. Suspension or Premature Termination
The Sponsor will suspend or terminate the study when so instructed by the IRB or FDA, or if
it is judged that the subjects are subjected to unreasonable risks, or for valid scientific or 
administrative reasons.
The Sponsor may also decide to close a single study site due to unsatisfactory subject
enrollment or non-compliance with the CIP, GCP, or applicable regulatory requirements.
In the event of premature termination, the Sponsor will provide information on the handling
of currently enrolled subjects who have not completed the study.
                                                
5 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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16. References
N/A
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SIGNATURES PAGE
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